Ampelopsin induces MDA-MB-231 cell cycle arrest through cyclin B1-mediated PI3K/AKT/mTOR pathway in vitro and in vivo

Abstract

Breast cancer is one of the most common malignant tumors in women and it is the most frequently diagnosed cancer in the world. Ampelopsin (AMP) is a purified component from the root of Ampelopsis grossedentata. It is reported that AMP could significantly inhibit the proliferation of breast cancer cells. However, the antitumor mechanism against breast cancer has not yet been fully elucidated. The purpose of this work was to study the role of AMP against breast cancer MDA-MB-231 cells and to further investigate the underlying mechanism. PI3K/AKT/mTOR plays a very important role in tumor cell growth and proliferation and we hypothesize that AMP may inhibit this pathway. In the present work, the results showed that AMP could significantly inhibit the growth of breast cancer MDA-MB-231 cells in vitro and in vivo. In addition, treatment with AMP decreased the levels of PI3K, AKT and mTOR, as well as cyclin B1 expression, followed by p53/p21 pathway activation to arrest the cell cycle at G2/M. Moreover, it demonstrated a positive association between cyclin B1 and PI3K/AKT/mTOR levels. Importantly, this pathway was found to be regulated by cyclin B1 in MDA-MB-231 cells treated with AMP. Also, it was observed that cyclin B1 overexpression attenuated cell apoptosis and weakened the inhibitory effects of AMP on cell proliferation. Together, AMP could inhibit breast cancer MDA-MB-231 cell proliferation in vitro and in vivo, due to cell cycle arrest at G2/M by inactivating PI3K/AKT/mTOR pathway regulated by cyclin B1.

Elucidation of the mechanism of action of ailanthone in the treatment of colorectal cancer: integration of network pharmacology, bioinformatics analysis and experimental validation

“…CCNB1 shRNA arrests CRC cells in the G2/M phase, thereby inhibiting their growth ( Fang et al, 2014 ). The inhibition of CCNB1 expression has also been reported to inactivate PI3K/AKT signaling and induce G2/M arrest ( Meng et al, 2023 ). Moreover, elevated CCNA1 and CCNA2 expression levels activates the PI3K/AKT pathway, promoting tumor growth and cell survival ( Talaat et al, 2022 ).…”