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 in: Parasitology Vol. 131; no. 2; pp. 215 - 230
• Main Authors: JAYANARAYAN, K. G., DEY, C. S.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.08.2005
• Subjects: Animals; Antiprotozoal Agents - pharmacology; Apoptosis; Apoptosis - drug effects; arsenite resistance; Arsenites - pharmacology; Cells; Chemicals; combination; DNA Fragmentation; Drug Resistance - physiology; Drug Therapy, Combination; Drugs; Gene Expression - drug effects; Industrial research; Investigations; Leishmania; Leishmania donovani - drug effects; Leishmania donovani - metabolism; Mortality; paclitaxel; Paclitaxel - pharmacology; Parasites; Protein Processing, Post-Translational; Scholarships & fellowships; Sodium arsenite; Sodium Compounds - pharmacology; Studies; Trifluralin; Trifluralin - pharmacology; Tubulin - drug effects; Tubulin - metabolism; tubulins; paclitaxel; trifluralin; Leishmania; tubulins; apoptosis; arsenite resistance; combination
• ISSN: 0031-1820; 1469-8161
• DOI: 10.1017/S0031182005007687

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.