title: Alisol F 24 Acetate Enhances Chemosensitivity and Apoptosis of MCF-7/DOX Cells by Inhibiting P-Glycoprotein-Mediated Drug Efflux.
abstract: Multidrug resistance (MDR) is a prime reason for numerous failed oncotherapy approaches. In the present study, we investigated whether Alisol F 24 acetate (ALI) could reverse the MDR of MCF-7/DOX cells, a multidrug-resistant human breast cancer cell line. We found that ALI was a potent P-glycoprotein (P-gp) inhibitor, in the Caco-2-monolayer cell model. ALI showed a significant and concentration-dependent cytotoxic effect on MCF-7/DOX cells in combination with doxorubicin by increasing intracellular accumulation and inducing nuclear migration of doxorubicin. However, ALI had no such effect on MCF-7 cells. In addition, ALI also promoted doxorubicin-induced early apoptosis of MCF-7/DOX cells in a time-dependent manner. These results suggest that ALI can enhance chemosensitivity of doxorubicin and reinforce its anti-cancer effect by increasing its uptake, especially inducing its nuclear accumulation in MCF-7/DOX cells. Therefore, ALI could be developed as a potential MDR-reversing agent in cancer chemotherapy in further study.
authors: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. guixiangp@163.com.
authors: Guixiang
authors: G
authors: Pan
authors: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. litingting2559@163.com.|Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China. litingting2559@163.com.
authors: Tingting
authors: T
authors: Li
authors: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. zengqing20080629@126.com.|Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China. zengqing20080629@126.com.
authors: Qingqing
authors: Q
authors: Zeng
authors: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. xiaoming_w@yeah.net.
authors: Xiaoming
authors: X
authors: Wang
authors: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. yanzhu.harvard@icloud.com.
authors: Yan
authors: Y
authors: Zhu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004077:Digoxin / Q000494:pharmacology; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D014315:Triterpenes; C000611953:alisol F 24-acetate; D004077:Digoxin; D004317:Doxorubicin
keywords: P-glycoprotein (P-gp); alisol F 24-acetate (ALI); doxorubicin; multidrug resistance (MDR)