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Therapeutic and preventive properties of honey and its bioactive compounds in cancer: an evidence-based review

  • Sadia Afrin (a1), Shoja M. Haneefa (a2), Maria J. Fernandez-Cabezudo (a3), Francesca Giampieri (a1) (a4), Basel K. al-Ramadi (a2) and Maurizio Battino (a1) (a4) (a5)...

Abstract

Despite the much improved therapeutic approaches for cancer treatment that have been developed over the past 50 years, cancer remains a major cause of mortality globally. Considerable epidemiological and experimental evidence has demonstrated an association between ingestion of food and nutrients with either an increased risk for cancer or its prevention. There is rising interest in exploring agents derived from natural products for chemoprevention or for therapeutic purposes. Honey is rich in nutritional and non-nutritional bioactive compounds, as well as in natural antioxidants, and its potential beneficial function in human health is becoming more evident. A large number of studies have addressed the anti-cancer effects of different types of honey and their phenolic compounds using in vitro and in vivo cancer models. The reported findings affirm that honey is an agent able to modulate oxidative stress and has anti-proliferative, pro-apoptotic, anti-inflammatory, immune-modulatory and anti-metastatic properties. However, despite its reported anti-cancer activities, very few clinical studies have been undertaken. In the present review, we summarise the findings from different experimental approaches, including in vitro cell cultures, preclinical animal models and clinical studies, and provide an overview of the bioactive profile and bioavailability of the most commonly studied honey types, with special emphasis on the chemopreventive and therapeutic properties of honey and its major phenolic compounds in cancer. The implications of these findings as well as the future prospects of utilising honey to fight cancer will be discussed.

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Corresponding author

*Corresponding authors: Basel K. al-Ramadi, fax +971 3 767 1966, email Ramadi.b@uaeu.ac.ae; Maurizio Battino, fax +39 71 220 4123, email m.a.battino@univpm.it

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These authors contributed equally to the present study.

Present address: Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.

§

Co-senior authors.

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References

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1. Castro-Vázquez, L, Díaz-Maroto, MC & Pérez-Coello, MS (2006) Volatile composition and contribution to the aroma of Spanish honeydew honeys. Identification of a new chemical marker. J Agric Food Chem 54, 48094813.
2. Manyi-Loh, CE, Ndip, RN & Clarke, AM (2011) Volatile compounds in honey: a review on their involvement in aroma, botanical origin determination and potential biomedical activities. Int J Mol Sci 12, 95149532.
3. Martinotti, S & Ranzato, E (2018) Honey, wound repair and regenerative medicine. J Funct Biomat 9, E34.
4. Alvarez-Suarez, JM, Tulipani, S, Díaz, D, et al. (2010) Antioxidant and antimicrobial capacity of several monofloral Cuban honeys and their correlation with color, polyphenol content and other chemical compounds. Food Chem Toxicol 48, 24902499.
5. Afrin, S, Gasparrini, M, Forbes-Hernández, TY, et al. (2018) Protective effects of manuka honey on LPS-treated RAW 264.7 macrophages. Part 1: Enhancement of cellular viability, regulation of cellular apoptosis and improvement of mitochondrial functionality. Food Chem Toxicol 121, 203213.
6. Gasparrini, M, Afrin, S, Forbes-Hernández, TY, et al. (2018) Protective effects of manuka honey on LPS-treated RAW 264.7 macrophages. Part 2: Control of oxidative stress induced damage, increase of antioxidant enzyme activities and attenuation of inflammation. Food Chem Toxicol 120, 578587.
7. Alvarez-Suarez, JM, Giampieri, F & Battino, M (2013) Honey as a source of dietary antioxidants: structures, bioavailability and evidence of protective effects against human chronic diseases. Curr Med Chem 20, 621638.
8. Almasaudi, SB, El-Shitany, NA, Abbas, AT, et al. (2016) Antioxidant, anti-inflammatory, and antiulcer potential of manuka honey against gastric ulcer in rats. Oxid Med Cell Longev 2016, 3643824.
9. Badolato, M, Carullo, G, Cione, E, et al. (2017) From the hive: honey, a novel weapon against cancer. Eur J Med Chem 142, 290299.
10. Miguel, MG, Antunes, MD & Faleiro, ML (2017) Honey as a complementary medicine. Integr Med Insights 12, 1178633717702869.
11. Byeongsang, OH, Butow, P, Mullan, B, et al. (2010) The use and perceived benefits resulting from the use of complementary and alternative medicine by cancer patients in Australia. Asia Pac J Clin Oncol 6, 342349.
12. Erejuwa, OO, Sulaiman, SA, Wahab, MSA (2014) Effects of honey and its mechanisms of action on the development and progression of cancer. Molecules 19, 24972522.
13. da Silva, PM, Gauche, C, Gonzaga, LV, et al. (2016) Honey: chemical composition, stability and authenticity. Food Chem 196, 309323.
14. Battino, M, Forbes-Hernández, TY, Gasparrini, M, et al. (2018) Relevance of functional foods in the Mediterranean diet: the role of olive oil, berries and honey in the prevention of cancer and cardiovascular diseases. Crit Rev Food Sci Nutr 59, 893920.
15. United States Department of Agriculture (2015) Full Report (All Nutrients): 19296, Honey. National Nutrient Database, Agricultural Research Service, Release 28. https://ndb.nal.usda.gov/ndb/foods/show/6287 (accessed October 2015).
16. Alvarez-Suarez, JM, Tulipani, S, Romandini, S, et al. (2010) Contribution of honey in nutrition and human health: a review. Med J Nutr Metab 3, 1523.
17. Kamal, MA & Klein, P (2011) Determination of sugars in honey by liquid chromatography. Saudi J Biol Sci 18, 1721.
18. Soldatkin, OO, Peshkova, VM, Saiapina, OY, et al. (2013) Development of conductometric biosensor array for simultaneous determination of maltose, lactose, sucrose and glucose. Talanta 115, 200207.
19. Escuredo, O, Dobre, I, Fernández-González, M, et al. (2014) Contribution of botanical origin and sugar composition of honeys on the crystallization phenomenon. Food Chem 149, 8490.
20. Won, S-R, Lee, D-C, Ko, SH, et al. (2008) Honey major protein characterization and its application to adulteration detection. Food Res Int 41, 952956.
21. Truzzi, C, Annibaldi, A, Illuminati, S, et al. (2014) Determination of proline in honey: comparison between official methods, optimization and validation of the analytical methodology. Food Chem 150, 477481.
22. Iglesias, MT, De Lorenzo, C, Del Carmen Polo, M, et al. (2004) Usefulness of amino acid composition to discriminate between honeydew and floral honeys. Application to honeys from a small geographic area. J Agric Food Chem 52, 8489.
23. Manzanares, AB, García, ZH, Galdón, BR, et al. (2014) Physicochemical characteristics of minor monofloral honeys from Tenerife, Spain. LWT Food Sci Technol 55, 572578.
24. Hermosín, I, Chicón, RM & Cabezudo, MD (2003) Free amino acid composition and botanical origin of honey. Food Chem 83, 263268.
25. Bogdanov, S, Jurendic, T, Sieber, R, et al. (2008) Honey for nutrition and health: a review. J Am Coll Nutr 27, 677689.
26. Castro-Vázquez, L, Díaz-Maroto, MC & Pérez-Coello, MS (2007) Aroma composition and new chemical markers of Spanish citrus honeys. Food Chem 103, 601606.
27. Moniruzzaman, M, Amrah Sulaiman, S & Gan, SH (2017) Phenolic acid and flavonoid composition of Malaysian honeys. J Food Biochem 41, e12282.
28. Chua, LS, Rahaman, NLA, Adnan, NA, et al. (2013) Antioxidant activity of three honey samples in relation with their biochemical components. J Anal Methods Chem 2013, 313798.
29. Küçük, M, Kolaylı, S, Karaoğlu, Ş, et al. (2007) Biological activities and chemical composition of three honeys of different types from Anatolia. Food Chem 100, 526534.
30. Afrin, S, Giampieri, F, Gasparrini, M, et al. (2018) The inhibitory effect of manuka honey on human colon cancer HCT-116 and LoVo cell growth. Part 1: The suppression of cell proliferation, promotion of apoptosis and arrest of the cell cycle. Food Funct 9, 21452157.
31. Alvarez-Suarez, JM, Giampieri, F, Cordero, M, et al. (2016) Activation of AMPK/Nrf2 signalling by manuka honey protects human dermal fibroblasts against oxidative damage by improving antioxidant response and mitochondrial function promoting wound healing. J Funct Foods 25, 3849.
32. Afrin, S, Forbes-Hernandez, TY, Gasparrini, M, et al. (2017) Strawberry-tree honey induces growth inhibition of human colon cancer cells and increases ROS generation: a comparison with manuka honey. Int J Mol Sci 18, E613.
33. Spilioti, E, Jaakkola, M, Tolonen, T, et al. (2014) Phenolic acid composition, antiatherogenic and anticancer potential of honeys derived from various regions in Greece. PLOS ONE 9, e94860.
34. Nousias, P, Karabagias, IK & Riganakos, KA (2018) Deep inside polyphenols of Hellenic thyme honey. Austin J Nutri Food Sci 6, 1098.
35. Kıvrak, Ş & Kıvrak, İ (2017) Assessment of phenolic profile of Turkish honeys. Int J Food Prop 20, 864876.
36. Hussein, SZ, Yusoff, KM, Makpol, S, et al. (2011) Antioxidant capacities and total phenolic contents increase with γ irradiation in two types of Malaysian honey. Molecules 16, 63786395.
37. Socha, R, Juszczak, L, Pietrzyk, S, et al. (2011) Phenolic profile and antioxidant properties of Polish honeys. Int J Food Sci Technol 46, 528534.
38. Ranneh, Y, Ali, F, Zarei, M, et al. (2018) Malaysian stingless bee and tualang honeys: a comparative characterization of total antioxidant capacity and phenolic profile using liquid chromatography-mass spectrometry. LWT Food Sci Technol 89, 19.
39. Jaganathan, SK, Mandal, SM, Jana, SK, et al. (2010) Studies on the phenolic profiling, anti-oxidant and cytotoxic activity of Indian honey: in vitro evaluation. Nat Prod Res 24, 12951306.
40. Moise, A, Mărghitaş Liviu, A, Dezmirean, D, et al. (2013) Nutraceutical properties of Romanian heather honey. Nutr Food Sci 43, 218227.
41. Boussaid, A, Chouaibi, M, Rezig, L, et al. (2014) Physicochemical and bioactive properties of six honey samples from various floral origins from Tunisia. Arab J Chem 11, 265274.
42. Hossen, MS, Ali, MY, Jahurul, MHA, et al. (2017) Beneficial roles of honey polyphenols against some human degenerative diseases: a review. Pharmacol Rep 69, 11941205.
43. Petretto, GL, Cossu, M & Alamanni, MC (2015) Phenolic content, antioxidant and physico-chemical properties of Sardinian monofloral honeys. Int J Food Sci Technol 50, 482491.
44. Acevedo, F, Torres, P, Oomah, BD, et al. (2017) Volatile and non-volatile/semi-volatile compounds and in vitro bioactive properties of Chilean ulmo (Eucryphia cordifolia Cav.) honey. Food Res Int 94, 2028.
45. Hegazi, AG & Abd El-Hady, FK (2007) Influence of honey on the suppression of human low density lipoprotein (LDL) peroxidation (in vitro). Evid Based Complement Alternat Med 6, 113121.
46. Buba, F, Gidado, A & Shugaba, A (2013) Analysis of biochemical composition of honey samples from North-East Nigeria. Biochem Anal Biochem 2, 3.
47. Nweze, JA, Okafor, JI, Nweze, EI, et al. (2017) Evaluation of physicochemical and antioxidant properties of two stingless bee honeys: a comparison with Apis mellifera honey from Nsukka, Nigeria. BMC Res Notes 10, 566.
48. Porcza, LM, Simms, C & Chopra, M (2016) Honey and cancer: current status and future directions. Diseases 4, E30.
49. Ciulu, M, Spano, N, Pilo, MI, et al. (2016) Recent advances in the analysis of phenolic compounds in unifloral honeys. Molecules 21, 451.
50. Manach, C, Williamson, G, Morand, C, et al. (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81, 230S242S.
51. Manach, C, Scalbert, A, Morand, C, et al. (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79, 727747.
52. Schramm, DD, Karim, M, Schrader, HR, et al. (2003) Honey with high levels of antioxidants can provide protection to healthy human subjects. J Agric Food Chem 51, 17321735.
53. Seraglio, SKT, Valese, AC, Daguer, H, et al. (2017) Effect of in vitro gastrointestinal digestion on the bioaccessibility of phenolic compounds, minerals, and antioxidant capacity of Mimosa scabrella Bentham honeydew honeys. Food Res Int 99, 670678.
54. Aliyu, M, Odunola, OA, Farooq, AD, et al. (2013) Molecular mechanism of antiproliferation potential of acacia honey on NCI-H460 cell line. Nutr Cancer 65, 296304.
55. Fernandez-Cabezudo, MJ, El-Kharrag, R, Torab, F, et al. (2013) Intravenous administration of manuka honey inhibits tumor growth and improves host survival when used in combination with chemotherapy in a melanoma mouse model. PLOS ONE 8, e55993.
56. Aryappalli, P, Al-Qubaisi, SS, Attoub, S, et al. (2017) The IL-6/STAT3 signaling pathway is an early target of manuka honey-induced suppression of human breast cancer cells. Front Oncol 7, 167.
57. Pichichero, E, Cicconi, R, Mattei, M, et al. (2010) Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression. Int J Oncol 37, 973981.
58. Sadeghi-Aliabadi, H, Hamzeh, J & Mirian, M (2015) Investigation of Astragalus honey and propolis extract’s cytotoxic effect on two human cancer cell lines and their oncogen and proapoptotic gene expression profiles. Adv Biomed Res 4, 42.
59. Afrin, S, Giampieri, F, Forbes-Hernandez, TY, et al. (2018) Manuka honey synergistically enhances the chemopreventive effect of 5-fluorouracil on human colon cancer cells by inducing oxidative stress and apoptosis, altering metabolic phenotypes and suppressing metastasis ability. Free Radic Biol Med 126, 4154.
60. Tsiapara, AV, Jaakkola, M, Chinou, I, et al. (2009) Bioactivity of Greek honey extracts on breast cancer (MCF-7), prostate cancer (PC-3) and endometrial cancer (Ishikawa) cells: profile analysis of extracts. Food Chem 116, 702708.
61. Seyhan, MF, Yılmaz, E, Timirci-Kahraman, Ö, et al. (2017) Anatolian honey is not only sweet but can also protect from breast cancer: elixir for women from Artemis to present. IUBMB Life 69, 677688.
62. Wen, CTP, Hussein, SZ, Abdullah, S, et al. (2012) Gelam and nenas honeys inhibit proliferation of HT 29 colon cancer cells by inducing DNA damage and apoptosis while suppressing inflammation. Asian Pac J Cancer Prev 13, 16051610.
63. Tahir, AA, Sani, NFA, Murad, NA, et al. (2015) Combined ginger extract & gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells. Nutr J 14, 31.
64. Wee, LH, Morad, NA, Aan, GJ, et al. (2015) Mechanism of chemoprevention against colon cancer cells using combined gelam honey and ginger extract via mTOR and Wnt/β-catenin pathways. Asian Pac J Cancer Prev 16, 65496556.
65. Hakim, L, Alias, E, Makpol, S, et al. (2014) Gelam honey and ginger potentiate the anti cancer effect of 5-FU against HCT 116 colorectal cancer cells. Asian Pac J Cancer Prev 15, 46514657.
66. Moskwa, J, Borawska, MH, Markiewicz-Zukowska, R, et al. (2014) Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line. PLOS ONE 9, e90533.
67. Aliyu, M, Odunola, OA, Farooq, AD, et al. (2012) Acacia honey modulates cell cycle progression, pro-inflammatory cytokines and calcium ions secretion in PC-3 cell line. J Cancer Sci Ther 4, 401407.
68. Salleh, MAM, Eshak, Z & Ismail, WIW (2017) Acacia honey induces apoptosis in human breast adenocarcinoma cell lines (MCF-7). J Teknol 79, 916.
69. Afrin, S, Giampieri, F, Cianciosi, D, et al. (2019) Strawberry tree honey as a new potential functional food. Part 1: Strawberry tree honey reduces colon cancer cell proliferation and colony formation ability, inhibits cell cycle and promotes apoptosis by regulating EGFR and MAPKs signaling pathways. J Funct Foods 57, 439452.
70. Ghashm, AA, Othman, NH, Khattak, MN, et al. (2010) Antiproliferative effect of tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines. BMC Complement Altern Med 10, 49.
71. Fauzi, AN, Norazmi, MN & Yaacob, NS (2011) Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines. Food Chem Toxicol 49, 871878.
72. Man, N, Khuzaimi, NM, Hassan, R, et al. (2015) Antileukemic effect of tualang honey on acute and chronic leukemia cell lines. Biomed Res Int 2015, 307094.
73. Yaacob, NS, Nengsih, A & Norazmi, M (2013) Tualang honey promotes apoptotic cell death induced by tamoxifen in breast cancer cell lines. Evid Based Complement Alternat Med 2013, 989841.
74. Jaganathan, SK & Mandal, M (2010) Involvement of non-protein thiols, mitochondrial dysfunction, reactive oxygen species and p53 in honey-induced apoptosis. Invest New Drugs 28, 624633.
75. Morales, P & Haza, AI (2013) Antiproliferative and apoptotic effects of Spanish honeys. Pharmacogn Mag 9, 231237.
76. Kassim, M, Achoui, M, Mustafa, MR, et al. (2010) Ellagic acid, phenolic acids, and flavonoids in Malaysian honey extracts demonstrate in vitro anti-inflammatory activity. Nutr Res 30, 650659.
77. Hassan, MI, Mabrouk, GM, Shehata, HH, et al. (2012) Antineoplastic effects of bee honey and Nigella sativa on hepatocellular carcinoma cells. Integr Cancer Ther 11, 354363.
78. Hanaa, MR & Shaymaa, MMY (2011) Enhancement of the antitumor effect of honey and some of its extracts using adiponectin hormone. Aust J Basic Appl Sci 5, 100108.
79. Haza, AI & Morales, P (2013) Spanish honeys protect against food mutagen-induced DNA damage. J Sci Food Agric 93, 29953000.
80. Afrin, S, Giampieri, F, Gasparrini, M, et al. (2018) The inhibitory effect of manuka honey on human colon cancer HCT-116 and LoVo cell growth. Part 2: Induction of oxidative stress, alteration of mitochondrial respiration and glycolysis, and suppression of metastatic ability. Food Funct 9, 21582170.
81. Afrin, S, Forbes-Hernández, TY, Cianciosi, D, et al. (2019) Strawberry tree honey as a new potential functional food. Part 2: Strawberry tree honey increases ROS generation by suppressing Nrf2-ARE and NF-κB signaling pathways and decreases metabolic phenotypes and metastatic activity in colon cancer cells. J Funct Foods 57, 477487.
82. Liu, J-R, Ye, Y-L, Lin, T-Y, et al. (2013) Effect of floral sources on the antioxidant, antimicrobial, and anti-inflammatory activities of honeys in Taiwan. Food Chem 139, 938943.
83. Aziz, AA, Rady, HM, Amer, MA, et al. (2009) Effect of some honey bee extracts on the proliferation, proteolytic and gelatinolytic activities of the hepatocellular carcinoma Hepg2 cell line. Aus J Basic Appl Sci 3, 27542769.
84. Yazan, LS, Zali, M, Shyfiq, MF, et al. (2016) Chemopreventive properties and toxicity of kelulut honey in Sprague Dawley rats induced with azoxymethane. Biomed Res Int 2016, 4036926.
85. Jaganathan, SK, Mondhe, D, Wani, ZA, et al. (2010) Effect of honey and eugenol on Ehrlich ascites and solid carcinoma. Biomed Res Int 2010, 989163.
86. Jaganathan, SK, Mondhe, D, Wani, ZA, et al. (2014) Evaluation of selected honey and one of its phenolic constituent eugenol against L1210 lymphoid leukemia. Sci World J 2014, 912051.
87. El-kott, AF, Kandeel, AA, El-Aziz, SFA, et al. (2012) Anti-tumor effects of bee honey on PCNA and P53 expression in the rat hepatocarcinogenesis. Int J Cancer Res 8, 130139.
88. Moniruzzaman, M, Sulaiman, SA, Khalil, MI, et al. (2013) Evaluation of physicochemical and antioxidant properties of sourwood and other Malaysian honeys: a comparison with manuka honey. Chemistry Cent J 7, 138.
89. Fukuda, M, Kobayashi, K, Hirono, Y, et al. (2011) Jungle honey enhances immune function and antitumor activity. Evid Based Complement Alternat Med 2011, 908743.
90. Kadir, EA, Sulaiman, SA, Yahya, NK, et al. (2013) Inhibitory effects of tualang honey on experimental breast cancer in rats: a preliminary study. Asian Pac J Cancer Prev 14, 22492254.
91. Ahmed, S, Sulaiman, SA & Othman, NH (2017) Oral administration of tualang and manuka honeys modulates breast cancer progression in Sprague–Dawley rats model. Evid Based Complement Alternat Med 2017, 5904361.
92. Orsolić, N, Knezević, A, Sver, L, et al. (2003) Influence of honey bee products on transplantable murine tumours. Vet Comp Oncol 1, 216226.
93. Swellam, T, Miyanaga, N, Onozawa, M, et al. (2003) Antineoplastic activity of honey in an experimental bladder cancer implantation model: in vivo and in vitro studies. Int J Urol 10, 213219.
94. Tomasin, R & Cintra Gomes-Marcondes, MC (2011) Oral administration of aloe vera and honey reduces Walker tumour growth by decreasing cell proliferation and increasing apoptosis in tumour tissue. Phytother Res 25, 619623.
95. Attia, WY, Gabry, MS, El-Shaikh, KA, et al. (2008) The anti-tumor effect of bee honey in Ehrlich ascite tumor model of mice is coincided with stimulation of the immune cells. Egypt J Immunol 15, 169183.
96. Hegazi, AG, Abdel-Rahman, EH, Abd-Allah, F, et al. (2015) Influence of honey on immune status in mice-bearing Ehrlich carcinoma. J Clin Cell Immunol 6, 295.
97. Mabrouk, GM, Moselhy, SS, Zohny, SF, et al. (2002) Inhibition of methylnitrosourea (MNU) induced oxidative stress and carcinogenesis by orally administered bee honey and Nigella grains in Sprague Dawely rats. J Exp Clin Cancer Res 21, 341346.
98. Rao, S, Hegde, SK, Rao, P, et al. (2017) Honey mitigates radiation-induced oral mucositis in head and neck cancer patients without affecting the tumor response. Foods 6, E77.
99. Cho, HK, Jeong, YM, Lee, HS, et al. (2015) Effects of honey on oral mucositis in patients with head and neck cancer: a meta-analysis. Laryngoscope 125, 20852092.
100. Hawley, P, Hovan, A, McGahan, CE, et al. (2014) A randomized placebo-controlled trial of manuka honey for radiation-induced oral mucositis. Support Care Cancer 22, 751761.
101. Charalambous, M, Raftopoulos, V, Paikousis, L, et al. (2018) The effect of the use of thyme honey in minimizing radiation-induced oral mucositis in head and neck cancer patients: a randomized controlled trial. Eur J Oncol Nurs 34, 8997.
102. Xu, JL, Xia, R, Sun, ZH, et al. (2016) Effects of honey use on the management of radio/chemotherapy-induced mucositis: a meta-analysis of randomized controlled trials. Int J Oral Maxillofac Surg 45, 16181625.
103. Fogh, SE, Deshmukh, S, Berk, LB, et al. (2017) A randomized phase 2 trial of prophylactic manuka honey for the reduction of chemoradiation therapy-induced esophagitis during the treatment of lung cancer: results of NRG Oncology RTOG 1012. Int J Radiat Oncol Biol Phys 97, 786796.
104. Mofid, B, Rezaeizadeh, H, Termos, A, et al. (2014) Effect of processed honey and royal jelly on cancer-related fatigue: a double-blind randomized clinical trial. Electronic Physician 8, 24752482.
105. Hizan, NS, Hassan, NHM, Haron, J, et al. (2018) Tualang honey adjunct with anastrozole improve parenchyma enhancement of breast tissue in breast cancer patients: a randomized controlled trial. Integr Med Res 7, 322327.
106. Chan, CW, Deadman, BJ, Manley-Harris, M, et al. (2013) Analysis of the flavonoid component of bioactive New Zealand mānuka (Leptospermum scoparium) honey and the isolation, characterisation and synthesis of an unusual pyrrole. Food Chem 141, 17721781.
107. Khalil, MI, Alam, N, Moniruzzaman, M, et al. (2011) Phenolic acid composition and antioxidant properties of Malaysian honeys. J Food Sci 76, C921C928.
108. Ahmed, S & Othman, NH (2013) Review of the medicinal effects of tualang honey and a comparison with manuka honey. Malays J Med Sci 20, 613.
109. Czyżewska, U, Siemionow, K, Zaręba, I, et al. (2016) Proapoptotic activity of propolis and their components on human tongue squamous cell carcinoma cell line (CAL-27). PLOS ONE 11, e0157091.
110. Chen, K-S, Shi, M-D, Chien, C-S, et al. (2014) Pinocembrin suppresses TGF-β1-induced epithelial-mesenchymal transition and metastasis of human Y-79 retinoblastoma cells through inactivating αvβ3 integrin/FAK/p38α signaling pathway. Cell Biosci 4, 41.
111. Chen, Z, Rasul, A, Zhao, C, et al. (2013) Antiproliferative and apoptotic effects of pinocembrin in human prostate cancer cells. Bangladesh J Pharmacol 8, 255262.
112. Alday, E, Valencia, D, Carreño, AL, et al. (2015) Apoptotic induction by pinobanksin and some of its ester derivatives from Sonoran propolis in a B-cell lymphoma cell line. Chem Biol Interact 242, 3544.
113. Sassi, A, Maatouk, M, Bzéouich, IM, et al. (2018) Chrysin, a natural and biologically active flavonoid suppresses tumor growth of mouse B16F10 melanoma cells: in vitro and in vivo study. Chem Biol Interact 283, 1019.
114. Maasomi, ZJ, Soltanahmadi, YP, Dadashpour, M, et al. (2017) Synergistic anticancer effects of silibinin and chrysin in T47D breast cancer cells. Asian Pac J Cancer Prev 18, 12831287.
115. Yu, X-M, Phan, T, Patel, PN, et al. (2013) Chrysin activates Notch1 signaling and suppresses tumor growth of anaplastic thyroid carcinoma in vitro and in vivo . Cancer 119, 774781.
116. Lin, Y-M, Chen, C-I, Hsiang, Y-P, et al. (2018) Chrysin attenuates cell viability of human colorectal cancer cells through autophagy induction unlike 5-fluorouracil/oxaliplatin. Int J Mol Sci 19, E1763.
117. Xu, Y, Tong, Y, Ying, J, et al. (2018) Chrysin induces cell growth arrest, apoptosis, and ER stress and inhibits the activation of STAT3 through the generation of ROS in bladder cancer cells. Oncol Lett 15, 91179125.
118. Ryu, S, Lim, W, Bazer, FW, et al. (2017) Chrysin induces death of prostate cancer cells by inducing ROS and ER stress. J Cell Physiol 232, 37863797.
119. Wang, J, Wang, H, Sun, K, et al. (2018) Chrysin suppresses proliferation, migration, and invasion in glioblastoma cell lines via mediating the erK/nrf2 signaling pathway. Drug Des Devel Ther 12, 721733.
120. Celińska-Janowicz, K, Zaręba, I, Lazarek, U, et al. (2018) Constituents of propolis: chrysin, caffeic acid, p-coumaric acid, and ferulic acid induce PRODH/POX-dependent apoptosis in human tongue squamous cell carcinoma cell (CAL-27). Front Pharmacol 9, 336.
121. Yang, B, Huang, J, Xiang, T, et al. (2014) Chrysin inhibits metastatic potential of human triple-negative breast cancer cells by modulating matrix metalloproteinase-10, epithelial to mesenchymal transition, and PI3K/Akt signaling pathway. J Appl Toxicol 34, 105112.
122. Zhang, W, Tang, B, Huang, Q, et al. (2013) Galangin inhibits tumor growth and metastasis of B16F10 melanoma. J Cell Biochem 114, 152161.
123. Wang, H-X & Tang, C (2017) Galangin suppresses human laryngeal carcinoma via modulation of caspase-3 and AKT signaling pathways. Oncol Rep 38, 703714.
124. Cao, J, Wang, H, Chen, F, et al. (2016) Galangin inhibits cell invasion by suppressing the epithelial–mesenchymal transition and inducing apoptosis in renal cell carcinoma. Mol Med Rep 13, 42384244.
125. Zou, W-W & Xu, S-P (2018) Galangin inhibits the cell progression and induces cell apoptosis through activating PTEN and caspase-3 pathways in retinoblastoma. Biomed Pharmacother 97, 851863.
126. Choi, YJ, Lee, YH & Lee, S-T (2015) Galangin and kaempferol suppress phorbol-12-myristate-13-acetate-induced matrix metalloproteinase-9 expression in human fibrosarcoma HT-1080 cells. Mol Cells 38, 151155.
127. Huang, H, Chen, AY, Rojanasakul, Y, et al. (2015) Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis. J Funct Foods 15, 464475.
128. Yu, S, Gong, L-s, Li, N-f, et al. (2018) Galangin (GG) combined with cisplatin (DDP) to suppress human lung cancer by inhibition of STAT3-regulated NF-κB and Bcl-2/Bax signaling pathways. Biomed Pharmacother 97, 213224.
129. Kumar, R & Tiku, AB (2018) Galangin induces cell death by modulating the expression of glyoxalase-1 and Nrf-2 in HeLa cells. Chem Biol Interact 279, 19.
130. Xu, YX, Wang, B & Zhao, XH (2017) In vitro effects and the related molecular mechanism of galangin and quercetin on human gastric cancer cell line (SGC-7901). Pak J Pharm Sci 30, 12791287.
131. Wang, Y, Wu, J, Lin, B, et al. (2014) Galangin suppresses HepG2 cell proliferation by activating the TGF-β receptor/Smad pathway. Toxicology 326, 917.
132. Su, L, Chen, X, Wu, J, et al. (2013) Galangin inhibits proliferation of hepatocellular carcinoma cells by inducing endoplasmic reticulum stress. Food Chem Toxicol 62, 810816.
133. Han, K, Lang, T, Zhang, Z, et al. (2018) Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics. Sci Rep 8, 8537.
134. Anson, DM, Wilcox, RM, Huseman, ED, et al. (2018) Luteolin decreases epidermal growth factor receptor-mediated cell proliferation and induces apoptosis in glioblastoma cell lines. Basic Clin Pharmacol Toxicol 123, 678686.
135. Wang, S-W, Chen, Y-R, Chow, J-M, et al. (2018) Stimulation of Fas/FasL-mediated apoptosis by luteolin through enhancement of histone H3 acetylation and c-Jun activation in HL-60 leukemia cells. Mol Carcinog 57, 866877.
136. Fu, J, Chen, D, Zhao, B, et al. (2012) Luteolin induces carcinoma cell apoptosis through binding Hsp90 to suppress constitutive activation of STAT3. PLOS ONE 7, e49194.
137. Sonoki, H, Tanimae, A, Endo, S, et al. (2017) Kaempherol and luteolin decrease claudin-2 expression mediated by inhibition of STAT3 in lung adenocarcinoma A549 cells. Nutrients 9, E597.
138. Song, S, Su, Z, Xu, H, et al. (2017) Luteolin selectively kills STAT3 highly activated gastric cancer cells through enhancing the binding of STAT3 to SHP-1. Cell Death Dis 8, e2612.
139. Aneknan, P, Kukongviriyapan, V, Prawan, A, et al. (2014) Luteolin arrests cell cycling, induces apoptosis and inhibits the JAK/STAT3 pathway in human cholangiocarcinoma cells. Asian Pac J Cancer Prev 15, 50715076.
140. Hong, J, Fristiohady, A, Nguyen, CH, et al. (2018) Apigenin and luteolin attenuate the breaching of MDA-MB231 breast cancer spheroids through the lymph endothelial barrier in vitro . Front Pharmacol 9, 220.
141. Yang, M-Y, Wang, C-J, Chen, N-F, et al. (2014) Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDA-MB-231 cells by blocking STAT3. Chem Biol Interact 213, 6068.
142. Huang, X, Dai, S, Dai, J, et al. (2015) Luteolin decreases invasiveness, deactivates STAT3 signaling, and reverses interleukin-6 induced epithelial–mesenchymal transition and matrix metalloproteinase secretion of pancreatic cancer cells. Onco Targets Ther 8, 29893001.
143. Feng, X-Q, Rong, L-W, Wang, R-X, et al. (2018) Luteolin and sorafenib combination kills human hepatocellular carcinoma cells through apoptosis potentiation and JNK activation. Oncol Lett 16, 648653.
144. Gong, C, Yang, Z, Zhang, L, et al. (2018) Quercetin suppresses DNA double-strand break repair and enhances the radiosensitivity of human ovarian cancer cells via p53-dependent endoplasmic reticulum stress pathway. Onco Targets Ther 11, 1727.
145. Calgarotto, AK, Maso, V, Junior, GCF, et al. (2018) Antitumor activities of quercetin and green tea in xenografts of human leukemia HL60 cells. Sci Rep 8, 3459.
146. Granato, M, Rizzello, C, Montani, MSG, et al. (2017) Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways. J Nutr Biochem 41, 124136.
147. Mukherjee, A, Khuda-Bukhsh, AR (2015) Quercetin down-regulates IL-6/STAT-3 signals to induce mitochondrial-mediated apoptosis in a nonsmall-cell lung-cancer cell line, A549. J Pharmacopuncture 18, 1926.
148. Chen, Z, Huang, C, Ma, T, et al. (2018) Reversal effect of quercetin on multidrug resistance via FZD7/β-catenin pathway in hepatocellular carcinoma cells. Phytomedicine 43, 3745.
149. Yu, D, Ye, T, Xiang, Y, et al. (2017) Quercetin inhibits epithelial–mesenchymal transition, decreases invasiveness and metastasis, and reverses IL-6 induced epithelial–mesenchymal transition, expression of MMP by inhibiting STAT3 signaling in pancreatic cancer cells. Onco Targets Ther 10, 47194729.
150. Ding, Y, Chen, X, Wang, B, et al. (2018) Quercetin suppresses the chymotrypsin-like activity of proteasome via inhibition of MEK1/ERK1/2 signaling pathway in hepatocellular carcinoma HepG2 cells. Can J Physiol Pharm 96, 521526.
151. Li, N, Sun, C, Zhou, B, et al. (2014) Low concentration of quercetin antagonizes the cytotoxic effects of anti-neoplastic drugs in ovarian cancer. PLOS ONE 9, e100314.
152. Feng, J, Song, D, Jiang, S, et al. (2018) Quercetin restrains TGF-β1-induced epithelial–mesenchymal transition by inhibiting Twist1 and regulating E-cadherin expression. Biochem Biophys Res Commun 498, 132138.
153. Wang, R, Yang, L, Li, S, et al. (2018) Quercetin inhibits breast cancer stem cells via downregulation of aldehyde dehydrogenase 1A1 (ALDH1A1), chemokine receptor type 4 (CXCR4), mucin 1 (MUC1), and epithelial cell adhesion molecule (EpCAM). Med Sci Monit 24, 412420.
154. Rasul, A, Millimouno, FM, Ali Eltayb, W, et al. (2013) Pinocembrin: a novel natural compound with versatile pharmacological and biological activities. Biomed Res Int 2013, 379850.
155. Trakoontivakorn, G, Nakahara, K, Shinmoto, H, et al. (2001) Structural analysis of a novel antimutagenic compound, 4-hydroxypanduratin A, and the antimutagenic activity of flavonoids in a Thai spice, fingerroot (Boesenbergia pandurata Schult.) against mutagenic heterocyclic amines. J Agric Food Chem 49, 30463050.
156. Hsu, C-L, Yu, Y-S & Yen, G-C (2010) Anticancer effects of Alpinia pricei Hayata roots. J Agric Food Chem 58, 22012208.
157. Kumar, MAS, Nair, M, Hema, PS, et al. (2007) Pinocembrin triggers Bax-dependent mitochondrial apoptosis in colon cancer cells. Mol Carcinog 46, 231241.
158. Samarghandian, S, Afshari, JT & Davoodi, S (2011) Chrysin reduces proliferation and induces apoptosis in the human prostate cancer cell line pc-3. Clinics 66, 10731079.
159. Russo, A, Longo, R & Vanella, A (2002) Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin. Fitoterapia 73, S21S29.
160. Heo, MY, Sohn, SJ & Au, WW (2001) Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate. Mutat Res Rev Mutat Res 488, 135150.
161. Liu, D, You, P, Luo, Y, et al. (2018) Galangin induces apoptosis in MCF-7 human breast cancer cells through mitochondrial pathway and phosphatidylinositol 3-kinase/Akt inhibition. Pharmacology 102, 5866.
162. Lee, C-C, Lin, M-L, Meng, M, et al. (2018) Galangin induces p53-independent S-phase arrest and apoptosis in human nasopharyngeal carcinoma cells through inhibiting PI3K-AKT signaling pathway. Anticancer Res 38, 13771389.
163. Hayes, G, Wright, N, Gardner, SL, et al. (2018) Manuka honey and methylglyoxal increase the sensitivity of Staphylococcus aureus to linezolid. Lett Appl Microbiol 66, 491495.
164. Paramita, D & Wisnubroto, JDP (2018) Effect of methylglyoxal on reactive oxygen species, KI-67, and caspase-3 expression in MCF-7 cells. Exp Mol Pathol 105, 7680.
165. Du, J, Suzuki, H, Nagase, F, et al. (2000) Methylglyoxal induces apoptosis in Jurkat leukemia T cells by activating c-Jun N-terminal kinase. J Cell Biochem 77, 333344.
166. Chan, W-H, Wu, H-J & Shiao, N-H (2007) Apoptotic signaling in methylglyoxal-treated human osteoblasts involves oxidative stress, c-Jun N-terminal kinase, caspase-3, and p21-activated kinase 2. J Cell Biochem 100, 10561069.
167. Ghosh, A, Bera, S, Ray, S, et al. (2011) Methylglyoxal induces mitochondria-dependent apoptosis in sarcoma. Biochemistry (Mosc) 76, 11641171.
168. Tuorkey, MJ (2016) Molecular targets of luteolin in cancer. Eur J Cancer Prev 25, 6576.
169. Ward, AB, Mir, H, Kapur, N, et al. (2018) Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways. World J Surg Oncol 16, 108.
170. Li, S, Yuan, S, Zhao, Q, et al. (2018) Quercetin enhances chemotherapeutic effect of doxorubicin against human breast cancer cells while reducing toxic side effects of it. Biomed Pharmacother 100, 441447.
171. Li, X, Zhou, N, Wang, J, et al. (2018) Quercetin suppresses breast cancer stem cells (CD44+/CD24) by inhibiting the PI3K/Akt/mTOR-signaling pathway. Life Sci 196, 5662.

Keywords

Therapeutic and preventive properties of honey and its bioactive compounds in cancer: an evidence-based review

  • Sadia Afrin (a1), Shoja M. Haneefa (a2), Maria J. Fernandez-Cabezudo (a3), Francesca Giampieri (a1) (a4), Basel K. al-Ramadi (a2) and Maurizio Battino (a1) (a4) (a5)...

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