YAP activation attenuates toxicarioside G‑induced lethal autophagy arrest in SW480 colorectal cancer cells

Zhou,Limin; Wang,Jinyan; Liu,Jiaqi; Liang,Jiantang; Wang,Yansong; Cai,Qunfang; Huang,Yonghao

doi:10.3892/or.2021.8175

YAP activation attenuates toxicarioside G‑induced lethal autophagy arrest in SW480 colorectal cancer cells

Authors:
- Limin Zhou
- Jinyan Wang
- Jiaqi Liu
- Jiantang Liang
- Yansong Wang
- Qunfang Cai
- Yonghao Huang
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Affiliations: Key Laboratory of Tropical Translational Medicine of The Ministry of Education and Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical University, Haikou, Hainan 571199, P.R. China, Key Laboratory of Tropical Translational Medicine of The Ministry of Education and Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical University, Haikou, Hainan 571199, P.R. China, Hainan Haitai Biomedical Technology Co., Ltd., Haikou, Hainan 571199, P.R. China, School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan 571199, P.R. China
Published online on: August 27, 2021 https://doi.org/10.3892/or.2021.8175
Article Number: 224
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Toxicarioside G (TCG), a natural product isolated from Calotropis gigantea, has been found to exhibit potent anticancer effects. The present study aimed to investigate the effect of TCG on the SW480 colorectal cancer cell line and the role of autophagy and Yes1 associated transcriptional regulator (YAP) in the TCG‑mediated inhibition of cell proliferation and viability. Cell proliferation was detected using MTT, BrdU, colony formation and LDH release assays, while apoptosis was analyzed using flow cytometry and western blot analyses. Immunofluorescence and western blot analysis was used to determine TCG‑induced autophagy and YAP activation. Pharmacological inhibition and siRNA was used to investigate the role of autophagy and YAP in TCG‑mediated cell growth inhibition. The results revealed that TCG inhibited SW480 cell proliferation and viability, independent of apoptosis, and also induced autophagy. It was further demonstrated that TCG blocks autophagic flux, resulting in autophagy arrest in the SW480 cell line. The inhibition of autophagy restored the TCG‑mediated inhibition of cell proliferation and viability, suggesting that TCG may induce lethal autophagy arrest in the SW480 cell line. Furthermore, TCG induced YAP activation in the SW480 cell line. Inhibition of YAP activity enhanced the TCG‑mediated inhibition of cell proliferation and viability, suggesting that YAP may play a protective role in the TCG‑induced effects. In conclusion, the findings of the present study indicated that TCG may induce lethal autophagy arrest and activate YAP, which serves a protective role in the SW480 cell line. These results suggested that the combined targeting of TCG and YAP may represent a promising strategy for TCG‑mediated anticancer therapy.

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