title: Cepharanthine potently enhances the sensitivity of anticancer agents in K562 cells.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ikeda
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Che
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Mina
authors.initials: M
authors.lastname: Ushiyama
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Zheng
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okumura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Shibayama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hei-Cheul
authors.initials: HC
authors.lastname: Jeung
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Furukawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sumizawa
authors.forename: Misako
authors.initials: M
authors.lastname: Haraguchi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Akiyama
authors.forename: Katsushi
authors.initials: K
authors.lastname: Yamada
mesh_terms: 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
chemical_list: 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