Apigenin suppresses proliferation and bone metastasis of human breast cancer cells by inducing apoptosis, autophagy and modulation of the MEK/ERK signalling pathway
Zhiqiang Wu 1, 2,   Zhicheng Wang 3,   Yanchun Meng 1, 4,   Zhonghua Tao 1, 4,   Wangjun Yan 1, 2,   Yiqun Du 1, 4
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Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
Department of Thoracic Surgery, Xuanwei First People’s Hospital, Xuanwei, China
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
Submission date: 2020-04-20
Final revision date: 2020-07-15
Acceptance date: 2020-07-26
Online publication date: 2020-09-28
Although several studies have reported the anticancer properties of apigenin, the impact of apigenin on the proliferation and bone metastasis of breast cancer cells has not been examined. This study was therefore undertaken to investigate the anticancer and anti-metastatic effects of apigenin against breast cancer cells.

Material and methods:
The breast cancer SK-BR-3 and MB-157 cells were used in the study. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Acridine orange/ethidium bromide (AO/EB) and annexin V/PI assays were performed to detect apoptosis. Electron microscopy was employed for autophagy detection. Bone metastasis was detected in mice xenograft models.

The proliferation assay showed that apigenin causes a remarkable decrease in the proliferation of the SK-BR-3 breast cancer cells and an IC50 of 10 µM was observed for apigenin against the SK-BR-3 cells. The inhibition of SK-BR-3 proliferation was found to be due to apoptosis which was accompanied with the upregulation of Bax and downregulation of Bc-2. Apigenin also triggered the activation of autophagy in the SK-BR-3 cells as evident from the upregulated expression of LC3 II and Beclin 1. Furthermore, the transwell assays together with the in vivo studies showed that apigenin suppressed the bone metastasis of the human breast cancer cells.

Taken together, the findings of the present study point towards the potential of apigenin in treatment of metastatic breast cancer.