Overcoming CPT-11 resistance by using a biscoclaurine alkaloid, cepharanthine, to modulate plasma trans-membrane potential
✍ Scribed by Kenjiro Aogi; Masahiko Nishiyama; Ryungsa Kim; Naoki Hirabayashi; Tetsuya Toge; Akiko Mizutani; Kosuke Okada; Hidetaka Sumiyoshi; Yasuhiro Fujiwara; Michio Yamakido; Toshihisa Kusano; Toshiwo Andoh
- Book ID
- 101233360
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- French
- Weight
- 170 KB
- Volume
- 72
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Irinotecan, 7-ethyl-10-[4-(I-piperidino)-1-piperidino] carbonyloxycamptothecin, (CPT-11) resistance was overcome by using a biscoclaurine alkaloid, cepharanthine, in CPT-11and multidrug-resistant 50MT-1 cells. 50MT-1 cells were established from a mouse breast-cancer cell line, FM3A, by subjecting the cells to a low dose of CPT-11 continuously. 50MT-1 cells exhibited resistance to CPT-11 (40-fold in colony-formation assay) and to other drugs such as doxorubicin (11.7-fold) and etoposide (VP-16) (16.8-fold). The plasma trans-membrane potential was lower in 50MT-1 cells than in FM3A cells, although there were no differences in expressions of P-glycoprotein and of DNA topoisomerase-I and -II proteins. The lower membrane potential in 50MT-1 cells was augmented by co-treatment with a non-toxic dose of cepharanthine. CPT-11 resistance in 50MT-1 cells was overcome (5.0-to 1.4-fold, 6-hr exposure) by the co-treatment with cepharanthine through increasing intracellular accumulation of CPT-11. Resistance to doxorubicin and VP-16 was also overcome by cepharanthine treatment (2.5-to 0.69-fold and 4.2-to 1.4-fold respectively). We conclude that the modification of plasma trans-membrane potential by cepharanthine should be effective in overcoming CPT-11 and multidrug resistance in 50MT-1 cells. Int.