PMID- 32901853
OWN - NLM
STAT- MEDLINE
DCOM- 20210630
LR  - 20231213
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 46
IP  - 5
DP  - 2020 Nov
TI  - Autophagy inhibition enhances the inhibitory effects of ursolic acid on lung 
      cancer cells.
PG  - 1816-1826
LID - 10.3892/ijmm.2020.4714 [doi]
AB  - 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.
FAU - Wang, Min
AU  - Wang M
AD  - 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.
FAU - Yu, Hong
AU  - Yu H
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 
      100029, P.R. China.
FAU - Wu, Ran
AU  - Wu R
AD  - Guizhou University School of Medicine, Guiyang, Guizhou 550025, P.R. China.
FAU - Chen, Zhen-Yin
AU  - Chen ZY
AD  - Guizhou University School of Medicine, Guiyang, Guizhou 550025, P.R. China.
FAU - Hu, Qian
AU  - Hu Q
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 
      100029, P.R. China.
FAU - Zhang, Yan-Fei
AU  - Zhang YF
AD  - 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.
FAU - Gao, San-Hui
AU  - Gao SH
AD  - 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.
FAU - Zhou, Guang-Biao
AU  - Zhou GB
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20200828
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (Triterpenes)
RN  - 886U3H6UFF (Chloroquine)
SB  - IM
MH  - A549 Cells
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Autophagy-Related Protein 5/metabolism
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Chloroquine/pharmacology
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/metabolism
MH  - MCF-7 Cells
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Signal Transduction/drug effects
MH  - Triterpenes/*pharmacology
MH  - Ursolic Acid
PMC - PMC7521584
EDAT- 2020/09/10 06:00
MHDA- 2021/07/01 06:00
PMCR- 2020/08/28
CRDT- 2020/09/09 08:47
PHST- 2019/10/06 00:00 [received]
PHST- 2020/07/16 00:00 [accepted]
PHST- 2020/09/10 06:00 [pubmed]
PHST- 2021/07/01 06:00 [medline]
PHST- 2020/09/09 08:47 [entrez]
PHST- 2020/08/28 00:00 [pmc-release]
AID - ijmm-46-05-1816 [pii]
AID - 10.3892/ijmm.2020.4714 [doi]
PST - ppublish
SO  - Int J Mol Med. 2020 Nov;46(5):1816-1826. doi: 10.3892/ijmm.2020.4714. Epub 2020 
      Aug 28.