Amentoflavone triggers cell cycle G2/M arrest by interfering with microtubule dynamics and inducing DNA damage in SKOV3 cells

Zhang,Jinli; Li,Aiguo; Sun,Hanjing; Xiong,Xifeng; Qin,Shengnan; Wang,Pengzhen; Dai,Libing; Zhang,Zhi; Li,Xiaojian; Liu,Zhihe

doi:10.3892/ol.2020.12031

Amentoflavone triggers cell cycle G2/M arrest by interfering with microtubule dynamics and inducing DNA damage in SKOV3 cells

Authors:
- Jinli Zhang
- Aiguo Li
- Hanjing Sun
- Xifeng Xiong
- Shengnan Qin
- Pengzhen Wang
- Libing Dai
- Zhi Zhang
- Xiaojian Li
- Zhihe Liu
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Affiliations: Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong 510220, P.R. China, Department of Traditional Chinese Medicine, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong 510220, P.R. China, Department of Burn and Plastic Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong 510220, P.R. China
Published online on: August 27, 2020 https://doi.org/10.3892/ol.2020.12031
Article Number: 168
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer is the seventh most common cancer and the second most common cause of cancer‑associated mortality among gynecological malignancies worldwide. The combination of antimitotic agents, such as taxanes, and the DNA‑damaging agents, such as platinum compounds, is the standard treatment for ovarian cancer. However, due to chemoresistance, development of novel therapeutic strategies for the treatment of ovarian cancer remains critical. Amentoflavone (AMF) is a biflavonoid derived from the extracts of Selaginella tamariscina, which has been used as a Chinese herb for thousands of years. A previous study demonstrated that AMF inhibits angiogenesis of endothelial cells and induces apoptosis in hypertrophic scar fibroblasts. In order to check the influence of AMF on cell proliferation, the effects of AMF on cell cycle and DNA damage were measured by cell viability, flow cytometry, immunofluorescence and western blotting assays in SKOV3 cells, an ovarian cell line. In the present study, treatment with AMF inhibited ovarian cell proliferation, increased P21 expression, decreased CDK1/2 expression, interrupted the balance of microtubule dynamics and arrested cells at the G2 phase. Furthermore, treatment with AMF increased the expression levels of phospho‑Histone H2AX (γ‑H2AX; a variant of histone 2A, that belongs to the histone 2A family member X) and the DNA repair protein RAD51 homolog 1 (Rad51), indicating the occurrence of DNA damage since γ‑H2AX and Rad51 are both key markers of DNA damage. Consistent with previous findings, the results of the present study suggest that AMF is a potential therapeutic agent for the treatment of ovarian cancer. In addition, the effects of AMF on cell cycle arrest and DNA damage induction may be the molecular mechanisms by which AMF might exert its potential therapeutic benefits in ovarian cancer.

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