PMID- 30513793
OWN - NLM
STAT- MEDLINE
DCOM- 20190211
LR  - 20231005
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 23
IP  - 12
DP  - 2018 Dec 1
TI  - S5, a Withanolide Isolated from Physalis Pubescens L., Induces G2/M Cell Cycle 
      Arrest via the EGFR/P38 Pathway in Human Melanoma A375 Cells.
LID - 10.3390/molecules23123175 [doi]
LID - 3175
AB  - S5 is a withanolide natural product isolated from Physalis pubescens L. Our 
      previous experimental studies found that it has significant antitumor activity on 
      renal cell carcinoma. In the present study, the anti-melanoma effect of S5 and 
      the related molecular mechanism was first investigated. It was found that S5 
      induced an obvious growth inhibitory effect on human melanoma A375 cells with low 
      toxicity to human peripheral blood cells. Furthermore, the results demonstrated 
      that the cell death mode of S5 on A375 cells is not due to inducing apoptosis and 
      autophagy. However, there was a significant time-dependent increase in G2/M phase 
      after treatment of A375 with S5. Meanwhile, S5 could also decrease the protein 
      expression of Cdc25c, Cdc2, and CyclinB1, and increased the expression of p-P53 
      and P21, suggesting that S5 inhibited A375 cell death through G2/M phase arrest. 
      Moreover, the signal pathway factors P38, extracellular regulated protein kinases 
      (ERK), and epidermal growth factor receptor (EGFR) were observed taking part in 
      the S5-induced A375 cells growth inhibitory effect. In addition, suppressing P38 
      and EGFR reversed the cell proliferation inhibitory effect and G2/M cell cycle 
      arrest induced by S5 and inhibition of EGFR enhanced the downregulation of the 
      expression of P38 and p-P38, indicating that S5 induced A375 G2/M arrest through 
      the EGFR/P38 pathway. Briefly, this study explained for the first time the 
      mechanism of S5-induced A375 cell growth inhibition in order to provide the basis 
      for its clinical application in melanoma.
FAU - Fan, Yuqi
AU  - Fan Y
AD  - Department of Biochemistry, School of Integrative Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. m13132215207@163.com.
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. m13132215207@163.com.
FAU - Mao, Yiwei
AU  - Mao Y
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. 18702228257@163.com.
FAU - Cao, Shijie
AU  - Cao S
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. caoshijie@tjutcm.edu.cn.
FAU - Xia, Guiyang
AU  - Xia G
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. nyxiaguiyang@163.com.
AD  - Department of Pharmaceutical Chemistry, School of Chinese Materia Medica, Tianjin 
      University of Traditional Chinese Medicine, Tianjin, 300193, China. 
      nyxiaguiyang@163.com.
FAU - Zhang, Qiang
AU  - Zhang Q
AD  - Department of Biochemistry, School of Integrative Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. zhangqiang7@hotmail.com.
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. zhangqiang7@hotmail.com.
FAU - Zhang, Hongyang
AU  - Zhang H
AD  - Department of Biochemistry, School of Integrative Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. red318@126.com.
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. red318@126.com.
FAU - Qiu, Feng
AU  - Qiu F
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. fengqiu20070118@163.com.
AD  - Department of Pharmaceutical Chemistry, School of Chinese Materia Medica, Tianjin 
      University of Traditional Chinese Medicine, Tianjin, 300193, China. 
      fengqiu20070118@163.com.
FAU - Kang, Ning
AU  - Kang N
AD  - Department of Biochemistry, School of Integrative Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, 300193, China. kangndd@163.com.
LA  - eng
GR  - 21472138/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20181201
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Withanolides)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/chemistry/isolation & 
      purification/*pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - ErbB Receptors/*metabolism
MH  - G2 Phase Cell Cycle Checkpoints/*drug effects
MH  - Humans
MH  - Molecular Structure
MH  - Physalis/*chemistry
MH  - Signal Transduction/*drug effects
MH  - Withanolides/chemistry/isolation & purification/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC6321527
OTO - NOTNLM
OT  - EGFR
OT  - G2/M arrest
OT  - P38
OT  - S5
OT  - melanoma
COIS- The authors declare no conflict of interest.
EDAT- 2018/12/06 06:00
MHDA- 2019/02/12 06:00
PMCR- 2018/12/01
CRDT- 2018/12/06 06:00
PHST- 2018/10/23 00:00 [received]
PHST- 2018/11/25 00:00 [revised]
PHST- 2018/11/29 00:00 [accepted]
PHST- 2018/12/06 06:00 [entrez]
PHST- 2018/12/06 06:00 [pubmed]
PHST- 2019/02/12 06:00 [medline]
PHST- 2018/12/01 00:00 [pmc-release]
AID - molecules23123175 [pii]
AID - molecules-23-03175 [pii]
AID - 10.3390/molecules23123175 [doi]
PST - epublish
SO  - Molecules. 2018 Dec 1;23(12):3175. doi: 10.3390/molecules23123175.