PMID- 34986722
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20240229
IS  - 1475-6374 (Electronic)
IS  - 1475-6366 (Print)
IS  - 1475-6366 (Linking)
VI  - 37
IP  - 1
DP  - 2022 Dec
TI  - Inhibitory effect of roburic acid in combination with docetaxel on human prostate 
      cancer cells.
PG  - 542-553
LID - 10.1080/14756366.2021.2018684 [doi]
AB  - Roburic acid (ROB) is a naturally occurred tetracyclic triterpenoid, and the 
      anticancer activity of this compound has not been reported. Docetaxel (DOC) is 
      the first-line chemotherapeutic agent for advanced stage prostate cancer but 
      toxic side effects and drug resistance limit its clinical success. In this study, 
      the potential synergistic anticancer effect and the underlying mechanisms of ROB 
      in combination with DOC on prostate cancer were investigated. The results showed 
      that ROB and DOC in combination synergistically inhibited the growth of prostate 
      cancer cells. The combination also strongly induced apoptosis, and suppressed 
      cell migration, invasion and sphere formation. Mechanistic study showed that the 
      combined effects of ROB and DOC on prostate cancer cells were associated with 
      inhibition of NF-kappaB activation, down regulation of Bcl-2 and up regulation of 
      Bax. Knockdown of NF-kappaB by small interfering RNA (siRNA) significantly decreased 
      the combined effect of ROB and DOC. Moreover, we found that esomeprazole (ESOM), 
      a proton pump inhibitor (PPI), strongly enhanced the effectiveness of ROB and DOC 
      on prostate cancer cells in acidic culture medium. Since acidic micro environment 
      is known to impair the efficacy of current anticancer therapies, ESOM combined 
      with ROB and DOC may be an effective approach for improving the treatment of 
      prostate cancer patients.
FAU - Wang, Xiao
AU  - Wang X
AD  - School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, 
      China.
FAU - Xuetao, Xu
AU  - Xuetao X
AD  - School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, 
      China.
AD  - International Healthcare Innovation Institute (Jiangmen), Jiangmen City, 
      Guangdong Province, China.
FAU - Wu, Mengshuo
AU  - Wu M
AD  - School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, 
      China.
FAU - Wu, Panpan
AU  - Wu P
AD  - School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, 
      China.
AD  - International Healthcare Innovation Institute (Jiangmen), Jiangmen City, 
      Guangdong Province, China.
FAU - Sheng, Zhaojun
AU  - Sheng Z
AD  - School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, 
      China.
AD  - International Healthcare Innovation Institute (Jiangmen), Jiangmen City, 
      Guangdong Province, China.
FAU - Liu, Wenfeng
AU  - Liu W
AD  - School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, 
      China.
AD  - International Healthcare Innovation Institute (Jiangmen), Jiangmen City, 
      Guangdong Province, China.
FAU - Ma, Yan-Yan
AU  - Ma YY
AD  - School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, 
      China.
AD  - International Healthcare Innovation Institute (Jiangmen), Jiangmen City, 
      Guangdong Province, China.
FAU - Zhao, Den-Gao
AU  - Zhao DG
AD  - School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, 
      China.
AD  - International Healthcare Innovation Institute (Jiangmen), Jiangmen City, 
      Guangdong Province, China.
FAU - Zhang, Kun
AU  - Zhang K
AD  - School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, 
      China.
AD  - International Healthcare Innovation Institute (Jiangmen), Jiangmen City, 
      Guangdong Province, China.
FAU - Li, Dongli
AU  - Li D
AUID- ORCID: 0000-0001-9955-2304
AD  - School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, 
      China.
AD  - International Healthcare Innovation Institute (Jiangmen), Jiangmen City, 
      Guangdong Province, China.
FAU - Zheng, Xi
AU  - Zheng X
AD  - Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The 
      State University of New Jersey, Piscataway, NJ, USA.
FAU - Goodin, Susan
AU  - Goodin S
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Enzyme Inhib Med Chem
JT  - Journal of enzyme inhibition and medicinal chemistry
JID - 101150203
RN  - 0 (BCL2 protein, human)
RN  - 15H5577CQD (Docetaxel)
RN  - N3PA6559FT (Esomeprazole)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (roburic acid)
SB  - IM
MH  - Humans
MH  - Male
MH  - *Antineoplastic Combined Chemotherapy Protocols/chemical 
      synthesis/chemistry/pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - *Docetaxel/chemistry/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Screening Assays, Antitumor
MH  - Esomeprazole/chemistry/pharmacology
MH  - Molecular Structure
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - *Prostatic Neoplasms/drug therapy/metabolism/pathology
MH  - Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors/metabolism
MH  - Structure-Activity Relationship
MH  - Tumor Cells, Cultured
PMC - PMC8741252
OTO - NOTNLM
OT  - Prostate cancer
OT  - combination
OT  - docetaxel
OT  - roburic acid
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/01/07 06:00
MHDA- 2022/03/22 06:00
PMCR- 2022/01/05
CRDT- 2022/01/06 05:30
PHST- 2022/01/06 05:30 [entrez]
PHST- 2022/01/07 06:00 [pubmed]
PHST- 2022/03/22 06:00 [medline]
PHST- 2022/01/05 00:00 [pmc-release]
AID - 2018684 [pii]
AID - 10.1080/14756366.2021.2018684 [doi]
PST - ppublish
SO  - J Enzyme Inhib Med Chem. 2022 Dec;37(1):542-553. doi: 
      10.1080/14756366.2021.2018684.