PMID- 32903420
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  - Tambulin Targets Histone Deacetylase 1 Inhibiting Cell Growth and Inducing 
      Apoptosis in Human Lung Squamous Cell Carcinoma.
PG  - 1188
LID - 10.3389/fphar.2020.01188 [doi]
LID - 1188
AB  - There is an urgent unmet need to develop new therapeutics for lung squamous cell 
      carcinoma (LSCC) as the current gold standard treatment regimens are dominated by 
      chemotherapy. In this study, we observed the treatment effects of the natural 
      compound tambulin on LSCC and explored its mechanism of action. LSCC cell lines 
      H226 and H520 were cultured in vitro to observe the effects of tambulin on cell 
      proliferation and apoptosis. Western blotting was used to detect the expression 
      of histone deacetylase 1 (HDAC1) and apoptosis-related proteins. Cell derived 
      xenografts (CDX) of H226 and H520 in nude mice were established to examine the 
      inhibitory effects of tambulin in vivo. Results showed that tambulin inhibited 
      the proliferation of H226 and H520 cells in a dose-dependent manner and inhibited 
      the growth of CDX tumors. Tambulin also promoted the apoptosis of H226 and H520 
      cells, up-regulated the protein expression of cleaved caspase-3, cleaved 
      caspase-9 and Bax, and down-regulated HDAC1 and Bcl-2 protein expression. In 
      support of this, immunohistochemical analysis of CDX tumors from mice treated 
      with tambulin showed increased expression of cleaved caspase-3 and Bax, while the 
      expression of HDAC1 and Bcl-2 were decreased. What's more, when HDAC1 was 
      over-expressed via adenovirus transduction in H226 or H520 cells, the effects of 
      tambulin were significantly attenuated. Interestingly, we found that combining 
      tambulin with cisplatin treatment in CDX models was more effective than single 
      drug treatment, suggesting that tambulin may enhance the sensitivity of LSCC to 
      cisplatin. Taken together, this study proves that tambulin has a definite 
      therapeutic effect on LSCC. Mechanistically, tambulin downregulates HDAC1, which 
      in turn regulates the Bcl-2/caspase signaling pathway and promotes cancer cell 
      apoptosis.
CI  - Copyright (c) 2020 Wang, Liu and Zhao.
FAU - Wang, Wuming
AU  - Wang W
AD  - Department of Thoracic Surgery, Jiangxi Provincial Chest Hospital, Nanchang, 
      China.
FAU - Liu, Yuzhen
AU  - Liu Y
AD  - Department of Thoracic Surgery, Jiangxi Provincial Chest Hospital, Nanchang, 
      China.
FAU - Zhao, Long
AU  - Zhao L
AD  - Department of Thoracic Surgery, Jiangxi Provincial Chest Hospital, Nanchang, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20200812
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7434869
OTO - NOTNLM
OT  - B-cell lymphoma 2
OT  - apoptosis
OT  - caspase
OT  - histone deacetylase 1
OT  - lung squamous cell carcinoma
OT  - tambulin
EDAT- 2020/09/10 06:00
MHDA- 2020/09/10 06:01
PMCR- 2020/08/12
CRDT- 2020/09/09 17:54
PHST- 2020/06/15 00:00 [received]
PHST- 2020/07/22 00:00 [accepted]
PHST- 2020/09/09 17:54 [entrez]
PHST- 2020/09/10 06:00 [pubmed]
PHST- 2020/09/10 06:01 [medline]
PHST- 2020/08/12 00:00 [pmc-release]
AID - 10.3389/fphar.2020.01188 [doi]
PST - epublish
SO  - Front Pharmacol. 2020 Aug 12;11:1188. doi: 10.3389/fphar.2020.01188. eCollection 
      2020.