title: Apigenin enhances the cisplatin cytotoxic effect through p53-modulated apoptosis.
abstract: Epidemiological and experimental evidence suggests that dietary flavonoids, including apigenin, have anticancer roles. Apigenin has been reported to elevate p53, a critical molecule in the induction of apoptosis. The present study aimed to investigate whether apigenin, a dietary flavonoid, improves the cytotoxic effect of cisplatin in a cancer cell culture system, and to elucidate the mechanism of this effect. Multiple tumor cell types were treated with apigenin, cisplatin or both drugs. Cell viability was evaluated, and the cytotoxic effect was determined biochemically and microscopically. Treatment with apigenin increased cisplatin-induced DNA damage and the apoptosis of tumor cells in a p53-dependent manner. Apigenin, when used with cisplatin, inhibited cell proliferation and promoted mitogen-activated protein kinase activation and subsequent p53 phosphorylation, leading to p53 accumulation and upregulation of proapoptotic proteins. Cisplatin is one of the most commonly used chemotherapeutic drugs for malignant tumors, but resistance to this drug occurs. The current results therefore demonstrate that dietary flavonoids may diminish the resistance of cancers to cisplatin.
authors.affiliation: Department of Gastrointestinal Oncology, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.affiliation: Department of Gastrointestinal Oncology, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Haishi
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Department of Gastrointestinal Oncology, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Oncology, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China.
authors.forename: Likun
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Gastrointestinal Oncology, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Deng
authors.affiliation: Department of Gastrointestinal Oncology, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ba
keywords: apigenin; apoptosis; cancer; cisplatin; p53