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.
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.
Jayanarayan
K G
KG
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.4S IVAGAR, Punjab 160062, India.
Dey
C S
CS
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000494:pharmacology; D053938:DNA Fragmentation; D004351:Drug Resistance / Q000502:physiology*; D004359:Drug Therapy, Combination; D015870:Gene Expression / Q000187:drug effects; D007893:Leishmania donovani / Q000187:drug effects* / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D017670:Sodium Compounds / Q000494:pharmacology; D014274:Trifluralin / Q000494:pharmacology; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism*
D000981:Antiprotozoal Agents; D018053:Arsenites; D017670:Sodium Compounds; D014404:Tubulin; C017947:sodium arsenite; D014274:Trifluralin; D017239:Paclitaxel