PMID- 32277651
OWN - NLM
STAT- MEDLINE
DCOM- 20201209
LR  - 20220218
IS  - 2241-6293 (Electronic)
IS  - 1107-0625 (Linking)
VI  - 25
IP  - 1
DP  - 2020 Jan-Feb
TI  - Inhibition of cancer cell growth in cisplatin-resistant human oral cancer cells 
      by withaferin-A is mediated via both apoptosis and autophagic cell death, 
      endogenous ROS production, G2/M phase cell cycle arrest and by targeting 
      MAPK/RAS/RAF signalling pathway.
PG  - 332-337
AB  - PURPOSE: Oral cancer is one of the common oral cavity and pharynx cancers and its 
      treatment is limited by early metastasis, late diagnosis and emergence of drug 
      resistance. Herein we investigated the anticancer effects of Withaferin-A against 
      the cisplatin-resistant SCC-4 human oral cancer cells. METHODS: The proliferation 
      rate of the human oral cancer cells was evaluated by CCK-8 assay. Apoptotic cell 
      death was studied by acridine orange (AO) / ethidium bromide (EB) staining as 
      well as by flow cytometry using annexin V/propidium iodide (PI) staining. Cell 
      cycle analysis was performed by flow cytometry. Reactive oxygen species (ROS) 
      examination was carried out by flow cytometry. Protein expressions were 
      determined by immunoblotting. RESULTS: The results of the MTT assay showed that 
      Withaferin-A caused decrease in the proliferation of SCC-4 cells and exhibited an 
      IC50 of 14 microM. The anticancer effects of Withaferin-A were mainly due to the 
      induction of apoptosis which was linked with upsurge of Bax and depletion of 
      BCl-2. Annexin V/PI assay showed that the apoptotic cells were 0.75, 5.8, 12.4 
      and 22.66% at 0,7,14 and 28 microM concentrations of Withaferin-A. Withaferin-A also 
      caused increase in the ROS and decrease in the MMP levels of the SCC-4 cells. 
      Western blot analysis showed that the expression of LC3B II increased while of 
      p62 decreased remarkably upon treatment with Withaferin-A, suggestive of 
      autophagic cell death. Cell cycle analysis by flow cytometry showed that 
      Withaferin-A caused increase in the G2/M phase cells triggering arrest of cancer 
      cells at the G2/M checkpoint of the cell cycle. Finally, western blot analysis 
      showed that Withaferin-A blocked the MAPK/RAS/RAF signalling pathway in the SCC-4 
      cells. CONCLUSIONS: These results suggest that Withaferin-A may prove a potent 
      lead molecule in oral cancer treatment and warrants further investigations.
FAU - Yin, Xuelian
AU  - Yin X
AD  - Department of Stomatology, Affiliated Hospital of Chengde Medical University, 
      Chengde 067000, China.
FAU - Yang, Guang
AU  - Yang G
FAU - Ma, Dongjie
AU  - Ma D
FAU - Su, Zhejun
AU  - Su Z
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
PL  - Cyprus
TA  - J BUON
JT  - Journal of B.U.ON. : official journal of the Balkan Union of Oncology
JID - 100883428
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Withanolides)
RN  - L6DO3QW4K5 (withaferin A)
SB  - IM
RIN - JBUON 2021 November-December; 26(6): 2712
ECI - J BUON. 2021 Mar-Apr;26(2):647. PMID: 34077031
MH  - Autophagic Cell Death/*drug effects
MH  - Cell Cycle Checkpoints/*drug effects
MH  - G2 Phase Cell Cycle Checkpoints/*drug effects
MH  - Humans
MH  - M Phase Cell Cycle Checkpoints/*drug effects
MH  - MAP Kinase Signaling System/*drug effects
MH  - Mouth Neoplasms/*drug therapy/pathology
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction
MH  - Withanolides/pharmacology/*therapeutic use
EDAT- 2020/04/12 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/04/12 06:00
PHST- 2020/04/12 06:00 [entrez]
PHST- 2020/04/12 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PST - ppublish
SO  - J BUON. 2020 Jan-Feb;25(1):332-337.