AB4 inhibits Notch signaling and promotes cancer cell apoptosis in liver cancer

Xiang,Zhuo; Miao,Qing; Zhang,Jin; Liu,Guoxin; Xue,Shuyi; Liu,Xu; Zhang,Zhe; Shen,Lixia; Liu,Bangguo; Zhou,Yu; Miao,Ting; Liu,Yang

doi:10.3892/or.2021.8063

AB4 inhibits Notch signaling and promotes cancer cell apoptosis in liver cancer

Authors:
- Zhuo Xiang
- Qing Miao
- Jin Zhang
- Guoxin Liu
- Shuyi Xue
- Xu Liu
- Zhe Zhang
- Lixia Shen
- Bangguo Liu
- Yu Zhou
- Ting Miao
- Yang Liu
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Affiliations: Department of Pharmacy, Hospital 971 of The Navy of Chinese PLA, Qingdao, Shandong 266071, P.R. China, Department of Burn and Plastic Surgery, Hospital 971 of The Navy of Chinese PLA, Qingdao, Shandong 266071, P.R. China, Department of Pharmacy, The Third People's Hospital of Qingdao, Qingdao, Shandong 266071, P.R. China, Department of Pharmacy, Qingdao Central Hospital, Qingdao, Shandong 266071, P.R. China, Wuxi Center for Drug Safety Control, Wuxi, Jiangsu 214000, P.R. China, Department of Traditional Chinese Medicine, Hospital 971 of The Navy of Chinese PLA, Qingdao, Shandong 266071, P.R. China
Published online on: April 26, 2021 https://doi.org/10.3892/or.2021.8063
Article Number: 112
Copyright: © Xiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The etiology for liver cancer has been clearly defined. Unfortunately, therapeutic approaches for liver cancer are rather limited, and liver cancer is insensitive to chemotherapy and radiotherapy. Traditional Chinese medicine (TCM) has become a promising strategy for cancer treatment as TCM elicits broad spectrum anticancer activity. In the present study, we evaluated the anticancer efficacy of AB4, an extract from the medical herb Pulsatilla chinensis (Bunge) Regel, in liver cancer in vitro and in vivo. We found that AB4 readily dose‑ and time‑dependently inhibited liver cancer HepG2 and Huh‑7 cell proliferation and colony formation. Western blot and flow cytometry analyses suggested that AB4 treatment induced liver cancer cell apoptosis. Moreover, these findings could be readily recaptured in vivo, in which the AB4 regimen resulted in tumor suppression and cancer cell apoptosis in xenograft tumor‑bearing nude mice. Importantly, we noted that treatment with a Notch signaling inhibitor DAPT produced very similar anticancer efficacy in both HepG2 and Huh‑7 cell lines, and administration of DAPT also efficiently suppressed HepG2 xenograft outgrowth. To this end, we anticipated that AB4 and DAPT may act on the same signaling pathway, probably through inhibition of the Notch pathway. Indeed, we found decreased expression of Notch1 protein, as well as downstream targets Hes1 and Hey1, after AB4 treatment. Immunohistochemistry analysis further confirmed the suppression of Notch signaling in HepG2 xenograft‑bearing mice. Taken together, our study highlighted the anticancer efficacy of AB4 in liver cancer. We also provided preliminary data showing Notch as a therapeutic target of AB4. It would be interesting to investigate the anticancer efficacy of AB4 in other types of cancer with elevated Notch activity.

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