1. Academic Validation
  2. Autophagy inhibition enhances the inhibitory effects of ursolic acid on lung cancer cells

Autophagy inhibition enhances the inhibitory effects of ursolic acid on lung cancer cells

  • Int J Mol Med. 2020 Nov;46(5):1816-1826. doi: 10.3892/ijmm.2020.4714.
Min Wang 1 Hong Yu 2 Ran Wu 3 Zhen-Yin Chen 3 Qian Hu 2 Yan-Fei Zhang 1 San-Hui Gao 1 Guang-Biao Zhou 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
  • 2 School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, P.R. China.
  • 3 Guizhou University School of Medicine, Guiyang, Guizhou 550025, P.R. China.
Abstract

The aim of the present study was to identify natural compounds that bear significant anti‑tumor activity. Thus, the effects of 63 small molecules that were isolated from traditional Chinese medicinal herbs on A549 human non‑small cell lung Cancer (NSCLC) and MCF‑7 breast Cancer cells were examined. It was found that ursolic acid (UA), a natural pentacyclic triterpenoid, exerted significant inhibitory effect on these cells. Further experiments revealed that UA inhibited the proliferation of various lung Cancer cells, including the NSCLC cells, H460, H1975, A549, H1299 and H520, the human small cell lung Cancer (SCLC) cells, H82 and H446, and murine Lewis lung carcinoma (LLC) cells. UA induced the Apoptosis and Autophagy of NSCLC cells. The inhibition of the mammalian target of rapamycin (mTOR) signaling pathway, but not the activation of the extracellular signal‑regulated kinase 1/2 (ERK1/2) signaling pathway contributed to the UA‑induced Autophagy of NSCLC cells. Moreover, the inhibition of Autophagy by chloroquine (CQ) or siRNA for autophagy‑related gene 5 (ATG5) enhanced the UA‑induced inhibition of cell proliferation and promotion of Apoptosis, indicating that UA‑induced Autophagy is a pro‑survival mechanism in NSCLC cells. On the whole, these findings suggest that combination treatment with Autophagy inhibitors may be a novel strategy with which enhance the antitumor activity of UA in lung Cancer.

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