PMID- 28796245
OWN - NLM
STAT- MEDLINE
DCOM- 20180430
LR  - 20210821
IS  - 2041-4889 (Electronic)
VI  - 8
IP  - 8
DP  - 2017 Aug 10
TI  - Dioscin induces prostate cancer cell apoptosis through activation of estrogen 
      receptor-beta.
PG  - e2989
LID - 10.1038/cddis.2017.391 [doi]
AB  - Recent researches have shown that estrogen receptor-beta (ERbeta) activator may be a 
      potent anticancer agent for prostate cancer (PCa), and our previous study also 
      indicated that dioscin can upregulate the expression of ERbeta in MC3T3-E1 cell. In 
      the present work, the activity and mechanism of dioscin, a natural product, 
      against PCa were investigated. The results showed that dioscin markedly inhibited 
      cell viability, colony formation, motility and induced apoptosis in PC3 cells. 
      Moreover, dioscin disrupted the formation of PC3 cell-derived mammospheres and 
      reduced aldehyde dehydrogenase (ALDH) level and the CD133(+)/CD44(+) cells, 
      indicating that dioscin had a potent inhibitory activity on prostate cancer stem 
      cells (PCSCs). In vivo results also showed that dioscin significantly suppressed 
      the tumor growth of PC3 cell xenografts in nude mice. Furthermore, mechanism 
      investigation showed that dioscin markedly upregulated ERbeta expression level, 
      subsequently increased prolyl hydroxylase 2 level, decreased the levels of 
      hypoxia-inducible factor-1alpha, vascular endothelial growth factor A and BMI-1, and 
      thus induced cell apoptosis by regulating the expression levels of caspase-3 and 
      Bcl-2 family proteins. In addition, transfection experiment of ERbeta-siRNA further 
      indicated that diosicn showed excellent activity against PCa in vitro and in vivo 
      by increasing ERbeta expression level. The co-immunoprecipitation (Co-IP) results 
      further suggested that dioscin promoted the interaction of c-ABL and ERbeta, but did 
      not change c-ABL expression. Moreover, the molecular docking assay showed that 
      dioscin processed powerful affinity toward to ERbeta mainly through the strong 
      hydrogen bonding and hydrophobic effects, and the actions of dioscin on ERbeta 
      activation and tumor cells inhibition were significantly weakened in the 
      mutational (Phe-336, Phe-468) PC3 cells. Collectively, these findings proved that 
      dioscin exerted efficient anti-PCa activity via activation of ERbeta, which should 
      be developed as an efficient candidate in clinical for treating this cancer in 
      the future.
FAU - Tao, Xufeng
AU  - Tao X
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Xu, Lina
AU  - Xu L
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Yin, Lianhong
AU  - Yin L
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Han, Xu
AU  - Han X
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Qi, Yan
AU  - Qi Y
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Xu, Youwei
AU  - Xu Y
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Song, Shasha
AU  - Song S
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Zhao, Yanyan
AU  - Zhao Y
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Peng, Jinyong
AU  - Peng J
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20170810
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (AC133 Antigen)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 3B95U4OLWV (dioscin)
RN  - EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
RN  - EC 1.14.11.29 (Egln1 protein, rat)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase)
RN  - EC 3.4.22.- (Caspase 3)
RN  - K49P2K8WLX (Diosgenin)
SB  - IM
RIN - Cell Death Dis. 2021 Aug 20;12(9):800. PMID: 34417439
MH  - AC133 Antigen/metabolism
MH  - Aldehyde Dehydrogenase/metabolism
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Caspase 3/genetics/metabolism
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects/genetics
MH  - Diosgenin/*analogs & derivatives/pharmacology
MH  - Estrogen Receptor beta/*metabolism
MH  - Hyaluronan Receptors/metabolism
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases
MH  - Immunoprecipitation
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Procollagen-Proline Dioxygenase/metabolism
MH  - Prostatic Neoplasms/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - Rats
MH  - Signal Transduction/drug effects
PMC - PMC5596577
COIS- The authors declare no conflict of interest.
EDAT- 2017/08/11 06:00
MHDA- 2018/05/01 06:00
PMCR- 2017/08/01
CRDT- 2017/08/11 06:00
PHST- 2017/04/28 00:00 [received]
PHST- 2017/06/22 00:00 [revised]
PHST- 2017/07/10 00:00 [accepted]
PHST- 2017/08/11 06:00 [entrez]
PHST- 2017/08/11 06:00 [pubmed]
PHST- 2018/05/01 06:00 [medline]
PHST- 2017/08/01 00:00 [pmc-release]
AID - cddis2017391 [pii]
AID - 10.1038/cddis.2017.391 [doi]
PST - epublish
SO  - Cell Death Dis. 2017 Aug 10;8(8):e2989. doi: 10.1038/cddis.2017.391.