Modulation of multidrug resistance by cepharanthine in fresh human gastrointestinal tumor cells

• Published in: Oncology Vol. 54; no. 2; p. 153
• Main Authors: Hotta, T, Tanimura, H, Yamaue, H, Iwahashi, M, Tani, M, Tsunoda, T, Tamai, M, Noguchi, K, Mizobata, S, Arii, K, Terasawa, H
• Format: Journal Article
• Language: English
• Published: Switzerland 01-03-1997
• Subjects: Alkaloids - pharmacology; Antibiotics, Antineoplastic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; ATP-Binding Cassette, Sub-Family B, Member 1 - drug effects; Benzylisoquinolines; Colonic Neoplasms - drug therapy; Colonic Neoplasms - physiopathology; Doxorubicin - administration & dosage; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gastrointestinal Neoplasms - drug therapy; Gastrointestinal Neoplasms - physiopathology; Gene Expression Regulation, Neoplastic - drug effects; Humans; Stomach Neoplasms - drug therapy; Stomach Neoplasms - physiopathology
• ISSN: 0030-2414
• DOI: 10.1159/000227680

Resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance (MDR) gene. Cepharanthine (CEP) has been shown to circumvent multidrug resistance in P-glycoprotein-expressing cell lines. In the present study, we investigated the augmentation of DOX sensitivity by CEP using an MTT assay, and assessed the correlation between DOX sensitivity and P-glycoprotein expression by flow cytometry, in highly purified fresh human tumor cells obtained from 73 cancer patients. DOX sensitivity was decreased in proportion to P-glycoprotein expression. The cytotoxicity of DOX was increased by CEP in tumor cells possessing low DOX sensitivity. Moreover, there was a significant correlation between the effect of CEP on cytotoxicity and P-glycoprotein expression. Thus, CEP might be able to circumvent DOX resistance in cancer patients.