Celastrus orbiculatus extract triggers apoptosis and autophagy via PI3K/Akt/mTOR inhibition in human colorectal cancer cells

Yang,Lin; Liu,Yanqing; Wang,Mei; Qian,Yayun; Dai,Xiaojun; Zhu,Yaodong; Chen,Jue; Guo,Shiyu; Hisamitsu,Tadashi

doi:10.3892/ol.2016.5213

November-2016 Volume 12 Issue 5

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November-2016 Volume 12 Issue 5

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Article Open Access

Celastrus orbiculatus extract triggers apoptosis and autophagy via PI3K/Akt/mTOR inhibition in human colorectal cancer cells

Authors:
- Lin Yang
- Yanqing Liu
- Mei Wang
- Yayun Qian
- Xiaojun Dai
- Yaodong Zhu
- Jue Chen
- Shiyu Guo
- Tadashi Hisamitsu
View Affiliations / Copyright

Affiliations: Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China, Department of Physiology, School of Medicine, Showa University, Tokyo 142‑8555, Japan

Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 3771-3778
|
Published online on: September 29, 2016

https://doi.org/10.3892/ol.2016.5213
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Abstract

Celastrus orbiculatus is used as a folk medicine in China for the treatment of numerous diseases. The ethyl acetate extract of Celastrus orbiculatus (COE) also displays a wide range of anti‑cancer activities in the laboratory. However, the effectiveness of COE‑induced autophagy and its mechanism of action in colorectal cancer cells have not been investigated thus far. The present study analyzed the effect of COE on HT‑29 cell viability, apoptosis and autophagy using MTT assay, flow cytometry, transmission electron microscopy and western blotting. Additionally, the autophagy inhibitor 3‑methyladenine and the autophagy inducer rapamycin were used to further explore the effects of COE‑induced autophagy in HT‑29 cells. The present study also examined whether the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) signaling pathway was involved in the regulation of COE‑induced autophagy. The results revealed that COE inhibited HT‑29 cell proliferation and decreased cell survival in a time‑ and dose‑dependent manner, and that COE possessed the ability to induce both apoptosis and autophagy in HT‑29 cells. Furthermore, autophagy and apoptosis induced by COE synergized to inhibit colorectal cancer growth. In addition, COE treatment decreased the phosphorylation of Akt and its downstream effectors mTOR and p70S6K. Taken together, these results demonstrate that both autophagy and apoptosis were activated during COE treatment of HT‑29 cells, and that COE‑induced autophagy decreases the viability of HT‑29 cells via a mechanism that may depend on the PI3K/Akt/mTOR/p70S6K signaling pathway. Furthermore, compounds that induce autophagy administered in combination with COE may be an attractive strategy for enhancing the anti‑tumor potency of COE in colorectal cancer.

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