Cepharanthine potently enhances the sensitivity of anticancer agents in K562 cells.
A major impediment to cancer treatment is the development of resistance by the tumor. P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) are involved in multidrug resistance. In addition to the extrusion of chemotherapeutic agents through these transporters, it has been reported that there are differences in the intracellular distribution of chemotherapeutic agents between drug resistant cells and sensitive cells. Cepharanthine is a plant alkaloid that effectively reverses resistance to anticancer agents. It has been previously shown that cepharanthine is an effective agent for the reversal of resistance in P-gp-overexpressing cells. Cepharanthine has also been reported to have numerous pharmacological effects besides the inhibition of P-gp. It has also been found that cepharanthine enhanced sensitivity to doxorubicin (ADM) and vincristine (VCR), and enhanced apoptosis induced by ADM and VCR of P-gp negative K562 cells. Cepharanthine changed the distribution of ADM from cytoplasmic vesicles to nucleoplasm in K562 cells by inhibiting the acidification of cytoplasmic organelles. Cepharanthine in combination with ADM should be useful for treating patients with tumors.
Ikeda
Ryuji
R
Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Che
Xiao-Fang
XF
Yamaguchi
Tatsuya
T
Ushiyama
Mina
M
Zheng
Chun-Lei
CL
Okumura
Hiroshi
H
Takeda
Yasuo
Y
Shibayama
Yoshihiko
Y
Nakamura
Kazuo
K
Jeung
Hei-Cheul
HC
Furukawa
Tatsuhiko
T
Sumizawa
Tomoyuki
T
Haraguchi
Misako
M
Akiyama
Shin-ichi
S
Yamada
Katsushi
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000502:physiology; D000470:Alkaloids / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D044182:Benzylisoquinolines; D004317:Doxorubicin / Q000494:pharmacology; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology; D052117:Benzodioxoles
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D004317:Doxorubicin; D014750:Vincristine; C006947:cepharanthine; D052117:Benzodioxoles