期刊
PHYTOMEDICINE
卷 62, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2019.152973
关键词
Biflavone; Caspase; Apoptosis; MAPK; G2/M; Cervical cancer
资金
- National Natural Science Foundation of China [21775023]
- Fujian Provincial Natural Science Foundation [2018J01596, 2016J01371]
- Social Development Guiding Programs of Fujian Province of China [2017Y0042, 2018Y0011]
- Joint Funds for the Innovation of Science and Technology, Fujian Province [2017Y9123, 2016Y9047]
- Training project of Young Talents in Health System of Fujian Province [2016-ZQN-63, 2018-ZQN-3]
- Talents Cultivation Program of Health System in Fujian Province [2018-CX-39]
- program for Young Top-Notch Innovative Talents of Fujian Province of China
Background: Cervical cancer (CCa) represents the fourth most common cause of cancer-related death in women worldwide. CCa therapy is still a major clinical challenge worldwide. Finding and developing new anti-CCa chemotherapeutic drugs is a very significant issue. Delicaflavone is a rare biflavonoid from Selaginella doederleinii Hieron, which has shown strong anti-cancer activities in our preliminary screening. Purpose: The present study aimed to investigate the apoptotic effect and mechanism of delicaflavone against CCa. Methods: In this study, the effect and potential mechanism of delicaflavone against CCa were investigated in vitro and in vivo by MTT assay, TEM, flow cytometry, western blot assay, qPCR assay, immunofluorescence assay and the mouse xenograft tumor model. Results: It was confirmed that delicaflavone inhibited the proliferation of human CCa HeLa cells, and induced morphological changes, G2/M phase arrest and apoptosis in a dose- and time-dependent manner. HeLa cells treated with delicaflavone showed the loss of mitochondrial membrane potential, release of Cytochrome c, activation of caspases, alteration of Bax/Bcl-2 balance, and the inhibition of MAPK signaling cascades. Furthermore, delicaflavone significantly decreased tumor growth in a dose-dependent manner without apparent side effects in a xenograft tumor model of HeLa cells. Immunohistochemistry analysis confirmed the up-regulation of Caspase-9, Caspase-3, Box protein and down-regulation of Bcl-2 protein in the xenografts tumors, which was consistent with the results in vitro. Conclusion: The results of the current study show that apoptosis is induced by the mitochondrial pathway accompanying with G2/M cycle arrest and inhibition of MAPK signaling cascades in human CCa HeLa cells, which can be used as a promising therapeutic drug for CCa.
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