Vincristine resistance

Vincristine-resistant subline. All other parameters same as in note e. 

The Phase I studies of vindesine determined the maximum tolerated dose of the compound to be 3-4 mg/m (body surface area) when given once weekly (i.v.) 78). Mild leukopenia ensues, reaching a nadir after about 4 days, and is accompanied by neurotoxicity. Several patients responded to drug treatment during this initial trial, including several complete responders with acute leukemias and partial responders with malignant melanoma and non-Hodgkin s lymphoma. Subsequent studies indicated that vindesine was active in vincristine-resistant childhood lymphocytic leukemia and, when combined with cisplatin, was effective in... 

Vincristine resistance has been studied in Chinese hamster ovary cell lines cells resistant to vincristine also are resistant to vinblastine and vindesine. Suggestions were made that, in cells with relatively low levels of drug resistance, at least two prominent mechanisms of resistance can occur (22). In the first instance, cellular resistance may be attributable to membrane alterations that are reversible, functionally, by treatment with verapamil. In the second, resistance has been postulated to be due to an altered sensitivity of tubulin to the effects of the drugs the primary basis for postulating an altered interaction with tubulin was that a subgroup of cells resistant to vincristine showed enhanced sensitivity to taxol, a drug that can stabilize microtubules. It should be emphasized that differential sensitivities of tubulins from different tumor cells to the effects of vincristine or vinblastine has been proposed as a basis for the susceptibilities of cells to the cytotoxic effects of such drugs (23). Differences have been described in the electrophoretic patterns for tubulins obtained from vin-... 

The macrocyclic lactone antibiotic rhizoxin, obtained from a plant fungus, has been reported to have activity against vincristine-resistant cells, both in vitro and in vivo (34). Such observations are interesting in view of the similar effects of rhizoxin and vincristine on cell morphology and cell cycle distribution. 

Effect of Quinacrine on Activity of Vincristine against Vincristine-Resistant P388 Leukemia in Mice... 

In 1991, Kojiri et al. reported the isolation of BE-13793C (344), an alkaloid isomeric with the arcyriaflavins C (347) and D (348) (see Scheme 2.89), from the culture broth of Streptoverticillium moharaense strain BA 13793 collected in Seto, Aichi Perfecture, Japan. BE-13793C (344) showed strong inhibitory activity against topoisomerases I and II and inhibited the growth of doxorubicin-resistant or vincristine-resistant P-388 murine leukemia cell lines, as well as their parent P-388 cell line (330). 

Barancik, M., et al. 1994. Reversal effects of several Ca(2+)-entry blockers, neuroleptics and local anaesthetics on P-glycoprotein-mediated vincristine resistance of L1210/VCR mouse leukaemic cell line. Drugs Exp Clin Res 20 13. 

In vitro studies with several tumor cell lines have shown vitamin C to enhance the cytotoxic activity of doxorubicin, cisplatin, paclitaxel, dacarbazine, 5-FU, and bleomycin. Vitamin C has also been shown to increase drug accumulation and to partially reverse vincristine resistance of human nonsmall-cell lung cancer cells. 

Tsuruo T, Iida H, Tsukagoshi S, et al. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 1981 41(5) 1967-1972. 

Kiue A, Sano T, Suzuki KI, Inada H, Okumura M, Kikuchi J, Sato SI, Kohno K, Kuwano M (1990) Activities of newly synthesized dihydropyridines in overcoming of vincristine resistance, calcium antagonism, and inhibition of photoaffinity labeling of P-glycoprotein in rodents. Cancer Res 50 310-317... 

Tsuruo T, Oh-hara T, lida H, Tsukagoshi S, Sato Z, Matsuda I, Iwasaki S, Okuda S, Shimizu F, Sasagawa K, Fukami M, Fukuda K, Arakawa M. Rhizoxin, a macrocychc lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine-resistant sublines. Cancer Res. 1986 46 381-385. 

The bisindole alkaloids, conodiparines A-D (362-365) also showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (KB/VJ300, IC50 1-5 pg/ml) with the highest activity shown by conodiparine A (362) (ICjo 1.45 gg/ml) [237]. 

Retigeric acid A and retigeric acid B (Lobaria kurokawae) Human Pea LNCaP PC-3, DU 145 Human epidermoid KB and vincristine Resistant KB (KBA CR) Human ovarian 3-AO and cisplatin resistant 3-AO (3-AO/CDDP) Human benign prostate Epithelial RWPEI Human hTERT-RPEI Human breast MCF-7 Liu et al. (2010)... 

Lundurines are a new type of indole alkaloids, which are characterized by an unusual carbon skeleton (Fig. 4.7) [17, 18]. In addition, lundurines B and D have displayed in vitro cytotoxicity towards B16 melanoma cells (lundurine B IC50 2.8 pl/mL), and lundurine B is also proved effective in circumventing multidrug resistance in vincristine-resistant KB cells. 

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