PMID- 38374014
OWN - NLM
STAT- MEDLINE
DCOM- 20240221
LR  - 20240221
IS  - 0004-0614 (Print)
IS  - 0004-0614 (Linking)
VI  - 77
IP  - 1
DP  - 2024 Jan
TI  - Curcumin Enhances the Anti-Cancer Efficacy of CDK4/6 Inhibitors in Prostate 
      Cancer.
PG  - 57-66
LID - 10.56434/j.arch.esp.urol.20247701.8 [doi]
AB  - OBJECTIVE: This study aimed to investigate the potential of combining 
      cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with curcumin (Cur), a 
      natural compound known for its anti-aging properties, to enhance the anti-cancer 
      efficacy in prostate cancer (PCa). METHODS: The cell viability was determined by 
      cell counting kit-8 assay, colony forming assay and cell invasion. The cell cycle 
      and mRNA levels of p16 (cyclin dependent kinase inhibitor 2A, CDKN2A), p21 
      (cyclin dependent kinase inhibitor 1A, CDKN1A) and Rb (RB transcriptional 
      corepressor) were detected by flow cytometry and quantitative real-time 
      polymerase chain reaction, respectively. SA-beta-gal staining and interleukin 6 
      (IL6) mRNA levels were used to evaluate cell aging. Western blot was used to 
      detect mechanistic targets of rapamycin (mTOR) and signal transducer and 
      activator of transcription 3 (STAT3) pathways. Moreover, Sphere formation assay 
      and mRNA levels of aldehyde dehydrogenase (ALDH) 1A1, CD44 and Nanog were used to 
      determine cell stemness. RESULTS: The combination of LY2835219 (LY, CDK4/6 
      inhibitor) and Cur exhibited a synergistic inhibitory effect on PCa cell 
      proliferation (p < 0.01) and invasion (p < 0.01) and Rb gene expression (p < 
      0.05), as well as a synergistic promotive effect on p61 expression (p < 0.01), 
      p21 expression (p < 0.01) and cell cycle G1 arrest in PCa cells (p < 0.05) 
      compared with LY or Cur alone. LY and LY + Cur increased the SA-beta-gal-stained 
      cells (p < 0.01). mTOR (p < 0.01) and STAT3 pathway (p < 0.01) were decreased by 
      LY + Cur (p < 0.01). Furthermore, LY + Cur conditioned medium (CM) inhibited cell 
      stemness by decreasing cell spheres (p < 0.05), ALDH1A1 (p < 0.01), CD44 (p < 
      0.01) and Nanog (p < 0.01) compared with LY CM. CONCLUSIONS: The findings of this 
      study suggested that the combination of CDK4/6 inhibitor and curcumin may have 
      clinical implications for the treatment of PCa.
CI  - (c) 2024 The Author(s).
FAU - Zhao, Huandong
AU  - Zhao H
AD  - Department of Internal Medicine, Henan University of Traditional Chinese 
      Medicine, 450046 Zhengzhou, Henan, China.
FAU - Ding, Ruimin
AU  - Ding R
AD  - Department of Laboratory, The Third Affiliated Hospital of Henan University of 
      Traditional Chinese Medicine, 450000 Zhengzhou, Henan, China.
FAU - Han, Jiarui
AU  - Han J
AD  - Department of Nephrology, Second Clinical Medical College, Henan University of 
      Traditional Chinese Medicine, 450002 Zhengzhou, Henan, China.
LA  - eng
PT  - Journal Article
PL  - Spain
TA  - Arch Esp Urol
JT  - Archivos espanoles de urologia
JID - 0064757
RN  - IT942ZTH98 (Curcumin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Curcumin/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/pharmacology
MH  - Cell Proliferation
MH  - *Prostatic Neoplasms/drug therapy
MH  - RNA, Messenger/genetics/pharmacology
MH  - Cyclin-Dependent Kinase 4/genetics/metabolism
OTO - NOTNLM
OT  - CDK4/6 inhibitor
OT  - cancer stem cell
OT  - cellular aging
OT  - curcumin
OT  - prostate cancer
COIS- The authors declare no conflict of interest.
EDAT- 2024/02/20 11:50
MHDA- 2024/02/21 11:22
CRDT- 2024/02/19 23:38
PHST- 2024/02/21 11:22 [medline]
PHST- 2024/02/20 11:50 [pubmed]
PHST- 2024/02/19 23:38 [entrez]
AID - 1706774243758-474549231 [pii]
AID - 10.56434/j.arch.esp.urol.20247701.8 [doi]
PST - ppublish
SO  - Arch Esp Urol. 2024 Jan;77(1):57-66. doi: 10.56434/j.arch.esp.urol.20247701.8.