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Altered tubulin dynamics, localization and post-translational modifications in sodium arsenite resistant Leishmania donovani in response to paclitaxel, trifluralin and a combination of both and induction of apoptosis-like cell death

Published online by Cambridge University Press:  21 April 2005

K. G. JAYANARAYAN  and
C. S. DEY
K. G. JAYANARAYAN
Affiliation:
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S NAGAR, Punjab 160062, India
C. S. DEY
Affiliation:
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S NAGAR, Punjab 160062, India
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Abstract

In this study the anti-leishmanial activity and anti-microtubule effects of paclitaxel, trifluralin and a combination of paclitaxel and trifluralin have been tested in a wild type and sodium arsenite-resistant strain of Leishmania donovani. Both paclitaxel and trifluralin have been shown to be effective in limiting parasite growth. Specific alterations in morphology, tubulin polymerization dynamics, post-translational modifications and cellular distribution of the tubulins have been confirmed to be a part of the intracellular anti-microtubule-events that occur in arsenite-resistant L. donovani in response to these agents, ultimately leading to death of the parasite. DNA analyses of the drug-treated wild type and arsenite-resistant strains revealed an apoptosis-like death in response to paclitaxel and the combination but not to trifluralin. Data provide valuable information for further development of chemotherapeutic strategies based on anti-microtubule agents against drug resistant Leishmania parasites.

Keywords

Leishmaniatubulinspaclitaxeltrifluralincombinationapoptosisarsenite resistance
Type
Research Article
Information
Parasitology , Volume 131 , Issue 2 , August 2005 , pp. 215 - 230
Copyright
2005 Cambridge University Press

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