Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-28T17:15:01.613Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access Rights & Permissions [Opens in a new window]

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

AOE, K., KIURA, K., UEOKA, H., TABATA, M., MATSUMURA, T., CHIKAMORI, M., MATSUSHITA, A., KOHARA, H. & HARADA, M. ( 1999). Effect of docetaxel with cisplatin or vinorelbine on lung cancer cell lines. Anticancer Research 19, 291–299.Google Scholar
BERHE, N., WOLDAY, D., HAILER, A., ABRAHAM, Y., ALI, A., GERBRE-MICHAEL, T., DESJEUX, P., SONNERBORG, A., AKUFFO, H. & BRITTON, S. ( 1999). HIV viral load and response to antileishmanial chemotherapy in co-infected patients. AIDS 13, 1921–1925.CrossRefGoogle Scholar
BHATTACHARYA, G., SALEM, M. & WERBOVETZ, K. ( 2002). Antileishmanial dinitroaniline sulfonamides with activity against parasite tubulin. Bioorganic Medicinal Chemistry Letters 12, 2395–2398.CrossRefGoogle Scholar
BLANCO, J. M. F., MOREIRA, M. E. C., BONOMO, A., BOZZA, P. T., MENDES, G. A., PRIMEZ, C. & BARCINSKI, M. A. ( 2001). Apoptotic mimicry by an obligate intracellular parasite downregulates macrophage microbicidal activity. Current Biology 11, 1870–1873.CrossRefGoogle Scholar
BUDMAN, D. R., CALABRO, A., WANG, L. G., LIU, X. M., STIEL, L., ADAMS, L. M. & KREIS, W. ( 2000). Synergism of cytotoxic effects of vinorelbine and paclitaxel in vitro. Cancer Investigation 18, 695–701.CrossRefGoogle Scholar
CHAN, M. M. & FONG, D. ( 1990). Inhibition of Leishmanias but not host macrophages by the antitubulin herbicide trifluralin. Science 249, 924–926.CrossRefGoogle Scholar
CHAN, M. M., GROGL, M., CHEN, C.-C., BIENEN, E. J. & FONG, D. ( 1993). Herbicides to curb human parasitic infections: In vitro and in vivo effects of trifluralin on the trypanosomatid protozoans. Proceedings of the National Academy of Sciences, USA 90, 5657–5661.CrossRefGoogle Scholar
CHAN, M. M., GROGL, M., CALLAHAN, H. & FONG, D. ( 1995). Efficacy of the herbicide trifluralin against four P-glycoprotein-expressing strains of Leishmania. Anti microbial Agents and Chemotherapy 39, 1609–1611.CrossRefGoogle Scholar
CULINE, S., ROCH, I., PINGUET, F., ROMIEU, G. & BRESSOLLE, F. ( 1999). Combination paclitaxel and vinorelbine therapy: in vitro cytotoxic interactions and dose-escalation study in breast cancer patients previously exposed to anthracyclines. International Journal of Oncology 14, 999–1006.CrossRefGoogle Scholar
DAS, M., MUKHERJEE, S. B. & SHAHA, C. ( 2001). Hydrogen peroxide induces apoptosis-like death in Leishmania donovani promastigotes. Journal of Cell Science 114, 2461–2469.Google Scholar
DEBRABANT, A., LEE, N., BERTHOLET, S., DUNCAN, R. & NAKHASI, H. L. ( 2003). Programmed cell death in trypanosomatids and other unicellular organisms. International Journal for Parasitology 33, 257–267.CrossRefGoogle Scholar
DIERAS, V., FUMOLEAU, P., KALLA, S., MILLET, J. L., AZLI, N. & POUILLART, P. ( 1997). Docetaxel in combination with doxorubicin or vinorelbine. European Journal of Cancer 33, S20–S22.CrossRefGoogle Scholar
DUMONTET, C. ( 2000). Mechanism of action and resistance to tubulin binding agents. Expert Opinion in Investigational Drugs 9, 779–788.CrossRefGoogle Scholar
GULL, K. ( 2001). The biology of kinetoplastid parasites: insights and challenges from genomics and post genomics. International Journal for Parasitology 31, 443–452.CrossRefGoogle Scholar
HANDMAN, E. ( 2001). Leishmaniasis: current status of vaccine. Clinical Microbiology Reviews 14, 229–243.CrossRefGoogle Scholar
HAVENS, C. G., BRYANT, N., ASHER, I., LAMOREAUX, L., PERFETTO, S., BRENDLE, J. J. & WERBOVETZ, K. A. ( 2000). Cellular effects of leishmanial tubulin inhibitors on L. donovani. Molecular and Biochemical Parasitology 110, 223–236.CrossRefGoogle Scholar
IRELAND, C. M. & PITTMAN, S. M. ( 1995). Tubulin alterations in taxol-induced apoptosis parallel those observed with other drugs. Biochemical Pharmacology 49, 1491–1499.CrossRefGoogle Scholar
JAYANARAYAN, K. G. & DEY, C. S. ( 2002). Resistance to arsenite modulates expression of beta- and gamma-tubulin and sensitivity to paclitaxel during differentiation of Leishmania donovani. Parasitology Research 88, 754–759.Google Scholar
JAYANARAYAN, K. G. & DEY, C. S. ( 2004). Altered expression, polymerization and cellular distribution of α-/β-tubulins and apoptosis-like cell death in arsenite resistant Leishmania donovani promastigotes. International Journal for Parasitology 34, 915–925.CrossRefGoogle Scholar
KAPOOR, P., GOSH, A. & MADHUBALA, R. ( 1999). Isolation of a taxol-resistant Leishmania donovani promastigote mutant that exhibits a multidrug-resistant phenotype. FEMS Microbiology Letters 176, 437–441.CrossRefGoogle Scholar
KAUR, J. & DEY, C. S. ( 2000). Putative P-Glycoprotein expression in arsenite resistant Leismania donovani down-regulated by verapamil. Biochemical and Biophysical Research Communications 271, 615–619.CrossRefGoogle Scholar
KHOL, L. & GULL, K. ( 1998). Molecular architecture of the trypanosome cytoskeleton. Molecular and Biochemical Parasitology 93, 1–9.CrossRefGoogle Scholar
KNICK, V. C., EBERWEIN, D. J. & MILLER, C. G. ( 1995). Vinorelbine tartrate and paclitaxel combinations: enhanced activity against in vivo P388 murine leukemia cells. Journal of the National Cancer Institute 87, 1027–1037.CrossRefGoogle Scholar
LAEMMLI, U. K. ( 1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227, 680–685.CrossRefGoogle Scholar
MacRAE, T. H. ( 1997). Tubulin post-translational modifications: Enzymes and their mechanisms of action. European Journal of Biochemistry 244, 265–278.CrossRefGoogle Scholar
MOULAY, L., ROBERT-GERO, M., BROWN, S., GENDRON, M.-C. & TOURNIER, F. ( 1996). Sinefungin and taxol effects on cell cycle and cytoskeleton of Leishmania donovani promastigotes. Experimental Cell Research 226, 283–291.CrossRefGoogle Scholar
OJIMA, I., DUCLOS, O., DORMAN, G., SMONOT, B., PRESTWICH, G. D., RAO, S., LERRO, K. A. & HORWITZ, S. B. ( 1995). A new paclitaxelphotoa.nity analog with a 3-(4-benzoylphenyl) propanoyl probe for characterization of drug binding sites on tubulin and P-glycoprotein. Journal of Medicinal Chemistry 38, 3891–3894.Google Scholar
PARIMOO, D., JEFFERS, S. & MUGGIA, F. M. ( 1996). Severe neurotoxicity from vinorelbine-paclitaxel combinations. Journal of National Cancer Institute 88, 1079–1080.CrossRefGoogle Scholar
PHOTIOU, A., SHAH, P., LEONG, L. K., MOSS, J. & RETSAS, S. ( 1997). In vitro synergy of paclitaxel (taxol) and vinorelbine (navelbine) against human melanoma cell lines. European Journal of Cancer 33, 463–470.CrossRefGoogle Scholar
PRASAD, V., KAUR, J. & DEY, C. S. ( 2000 a). Arsenite-resistant Leishmania donovani promastigotes express an enhanced membrane P-type adenoside triphosphatase activity that is sensitive to verapamil treatment. Parasitology Research 86, 838–842.Google Scholar
PRASAD, V., KUMAR, S. S. & DEY, C. S. ( 2000 b). Resistance to arsenite modulates levels of α-tubulin and sensitivity to paclitaxel in Leishmania donovani. Parasitology Research 86, 661–664.Google Scholar
ROBINSON, D. R., SHERWIN, T., PLOUBIDOU, A., BYARD, E. H. & GULL, K. ( 1995). Microtubule polarity and dynamics in the control of organelle positioning, segregation and cytokinesis in the trypanosome cell cycle. Journal of Cell Biology 128, 1163–1172.CrossRefGoogle Scholar
SAMBROOK, J., FRITSCH, E. F. & MANIATIS, T. ( 1989). Molecular Cloning: a Laboratory Manual, 2nd Edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor.
SASSE, R. & GULL, K. ( 1988). Tubulin post-translational modifications and the construction of microtubular organelles in Trypanosoma brucei. Journal of Cell Science 90, 577–589.Google Scholar
SCHNEIDER, A., PLESSMANN, U. & WEBER, K. ( 1997). Subpellicular and flagellar microtubules of Trypanosoma brucei are extensively glutamylated. Journal of Cell Science 110, 431–437.Google Scholar
SCHNEIDER, A., SHERWIN, T., SASSE, R., RUSSEL, D. G., GULL, K. & SEEBECK, T. ( 1987). Subpellicular and flagellar microtubules of Trypanosoma brucei brucei contain the same α-tubulin isoforms. Journal of Cell Biology 104, 431–438.CrossRefGoogle Scholar
SERENO, D., HOZMULLER, P., MANGOT, I., CUNY, G., OUAISSI, A. & LEMESRE, J. L. ( 2001). Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes. Antimicrobial Agents and Chemotherapy 45, 2064–2069.CrossRefGoogle Scholar
SHERWIN, T., SCHNEIDER, A., SASSE, R., SEEBECK, T. & GULL, K. ( 1987). Distinct localization and cell cycle dependence of COOH terminally tyrosinated α-tubulin in the microtubules of Trypanosoma brucei brucei. Journal of Cell Biology 104, 439–446.CrossRefGoogle Scholar
SNAPP, E. & LANDFEAR, S. M. ( 1997). Cytoskeletal association is important for differential targeting of glucose transporter isoforms in Leishmania. Journal of Cell Biology 139, 1775–1783.CrossRefGoogle Scholar
SULIMENKO, V., SULIMENKO, T., POZNANOVIC, S., NECHIPORUK-ZLOY, V., BOHM, K. J., MACUREK, L., UNGER, E. & DRABER, P. ( 2002). Association of brain gamma-tubulins with alpha beta-tubulin dimers. Biochemistry Journal 365, 889–895.CrossRefGoogle Scholar
VERMA, N. K. & DEY, C. S. ( 2004). Possible mechanism of miltefosine mediated death of Leishmania donovani. Antimicrobial Agents and Chemotherapy 48, 3010–3015.CrossRefGoogle Scholar
VOGEL, J., DRAPKIN, B., OOMEN, J., BEACH, D., BLOOM, K. & SNYDER, M. ( 2001). Phosphorylation of gamma-tubulin regulates microtubule organization in budding yeast. Development Cell 1, 621–631.CrossRefGoogle Scholar
WERBOVETZ, K. A. ( 2002). Tubulin as an antiprotozoal drug target. Mini Reviews in Medicinal Chemistry 2, 519–529.CrossRefGoogle Scholar
WERBOVETZ, K. A., BRENDLE, J. J. & SACKETT, D. L. ( 1999). Purification, characterization, and drug susceptibility of tubulin from Leishmania. Molecular and Biochemical Parasitology 98, 53–65.CrossRefGoogle Scholar
WERBOVETZ, K. A., SACKETT, D. L., DELFIN, D., BHATTACHARYA, G., SALEM, M., OBRZUT, T., RATTENDI, D. & BACCHI, C. ( 2003). Selective antimicrotubule activity of N1-phenyl-3,5-dinitro-N4,N4-di-n-propylsulfanilamide (GB-II-5) against kinetoplastid parasites. Molecular Pharmacology 64, 1325–1333.CrossRefGoogle Scholar
WESTERMANN, S. & WEBER, K. ( 2003). Post-translational modifications regulate microtubule function. Nature Reviews 4, 938–947.CrossRefGoogle Scholar
ZANGGER, H., MOTTRAM, J. C. & FASEL, N. ( 2002). Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis? Cell Death and Differentiation 9, 1126–1139.Google Scholar