PMID- 32903546
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - Uncovering the Mechanisms of Cryptotanshinone as a Therapeutic Agent Against 
      Hepatocellular Carcinoma.
PG  - 1264
LID - 10.3389/fphar.2020.01264 [doi]
LID - 1264
AB  - Hepatocellular carcinoma (HCC) is a fatal and dominant form of liver cancer that 
      currently has no effective treatment or positive prognosis. In this study, we 
      explored the antitumor effects of cryptotanshinone (CPT) against HCC and the 
      molecular mechanisms underlying these effects using a systems pharmacology and 
      experimental validation approach. First, we identified a total of 296 CPT 
      targets, 239 of which were also HCC-related targets. We elucidated the mechanisms 
      by which CPT affects HCC through multiple network analysis, including CPT-target 
      network analysis, protein-protein interaction network analysis, target-function 
      network analysis, and pathway enrichment analysis. In addition, we found that CPT 
      induced apoptosis in Huh7 and MHCC97-H ells due to increased levels of cleaved 
      PARP, Bax, and cleaved caspase-3 and decreased Bcl-2 expression. CPT also induced 
      autophagy in HCC cells by increasing LC3-II conversion and the expression of 
      Beclin1 and ATG5, while decreasing the expression of p62/SQSTM1. Autophagy 
      inhibitors (3-methyladenine and chloroquine) enhanced CPT-induced proliferation 
      and apoptosis, suggesting that CPT-induced autophagy may protect HCC cells 
      against cell death. Furthermore, CPT was found to inhibit the 
      phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of 
      rapamycin (mTOR) signaling pathway. Interestingly, activation of PI3K by 
      insulin-like growth factor-I inhibited CPT-induced apoptosis and autophagy, 
      suggesting that the PI3K/AKT/mTOR signaling pathway is involved in both 
      CPT-induced apoptosis and autophagy. Finally, CPT was found to inhibit the growth 
      of Huh7 xenograft tumors. In conclusion, we first demonstrated the antitumor 
      effects of CPT in Huh7 and MHCC97-H cells, both in vitro and in vivo. We 
      elucidated the potential antitumor mechanism of CPT, which involved inducing 
      apoptosis and autophagy by inhibiting the PI3K/Akt/mTOR signaling pathway. Our 
      findings may provide valuable insights into the clinical application of CPT, 
      serving as a potential candidate therapeutic agent for HCC treatment.
CI  - Copyright (c) 2020 Luo, Song, Wang, Huang, Liu, Wang, Hong and Yuan.
FAU - Luo, Yi
AU  - Luo Y
AD  - Science and Technology Innovation Center, Guangzhou University of Chinese 
      Medicine, Guangzhou, China.
AD  - Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Song, Lei
AU  - Song L
AD  - Science and Technology Innovation Center, Guangzhou University of Chinese 
      Medicine, Guangzhou, China.
AD  - Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Wang, Xinyu
AU  - Wang X
AD  - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 
      China.
FAU - Huang, Yujie
AU  - Huang Y
AD  - Science and Technology Innovation Center, Guangzhou University of Chinese 
      Medicine, Guangzhou, China.
AD  - Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Liu, Yongqiang
AU  - Liu Y
AD  - Science and Technology Innovation Center, Guangzhou University of Chinese 
      Medicine, Guangzhou, China.
AD  - Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Wang, Qi
AU  - Wang Q
AD  - Science and Technology Innovation Center, Guangzhou University of Chinese 
      Medicine, Guangzhou, China.
AD  - Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Hong, Ming
AU  - Hong M
AD  - Science and Technology Innovation Center, Guangzhou University of Chinese 
      Medicine, Guangzhou, China.
AD  - Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Yuan, Zhongyu
AU  - Yuan Z
AD  - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20200813
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7438559
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - cryptotanshinone
OT  - hepatocellular carcinoma
OT  - system pharmacology
EDAT- 2020/09/10 06:00
MHDA- 2020/09/10 06:01
PMCR- 2020/08/13
CRDT- 2020/09/09 17:55
PHST- 2020/05/20 00:00 [received]
PHST- 2020/07/30 00:00 [accepted]
PHST- 2020/09/09 17:55 [entrez]
PHST- 2020/09/10 06:00 [pubmed]
PHST- 2020/09/10 06:01 [medline]
PHST- 2020/08/13 00:00 [pmc-release]
AID - 10.3389/fphar.2020.01264 [doi]
PST - epublish
SO  - Front Pharmacol. 2020 Aug 13;11:1264. doi: 10.3389/fphar.2020.01264. eCollection 
      2020.