Bisdemethoxycurcumin Augments Docetaxel Efficacy for Treatment of Prostate Cancer

Biol Pharm Bull. 2024;47(8):1437-1446. doi: 10.1248/bpb.b24-00248.

Abstract

Bisdemethoxycurcumin (BDMC) is one of major forms of curcuminoids found in the rhizomes of turmeric. Docetaxel (DTX) is the standard of care for men diagnosed with androgen-independent prostate cancers. Here we report for the first time that BDMC could reinforce the effect of DTX against prostate cancer in vitro and in vivo. In vitro study, PC3 and LNCaP cells were cultured and treated with BDMC and DTX alone or in combination. The effects on cell viability were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by annexin V/propidium iodide (PI) staining, while cell cycle was assessed by PI staining. Bax, Bcl-2, caspase, poly(ADP-ribose)polymerase (PARP), cyclin B1 and CDK1 expression were assayed by Western blot. We found that a combination treatment of BDMC (10 µM) with DTX (10 nM) was more effective in the inhibition of PC3 and LNCaP cell growth and induction of apoptosis as well as G2/M arrest, which is accompanied with the significant inhibition of Bcl-2, cyclin B1, CDK1 expression and significant increase of Bax, cleaved caspase-9, cleaved caspase-3 and cleaved PARP, than those by treatment of BDMC or DTX alone. Moreover, in vivo evaluation further demonstrated the superior anticancer efficacy of BDMC and DTX compared to DTX alone in a murine prostate cancer model. These results suggest that BDMC can be an attractive therapeutic candidate in enhancing the efficacy of DTX in prostate cancer treatment.

Keywords: apoptosis; bisdemethoxycurcumin; cell cycle arrest; docetaxel.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis* / drug effects
  • CDC2 Protein Kinase / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Curcumin / analogs & derivatives
  • Curcumin / pharmacology
  • Curcumin / therapeutic use
  • Cyclin B1 / metabolism
  • Diarylheptanoids* / pharmacology
  • Diarylheptanoids* / therapeutic use
  • Docetaxel* / pharmacology
  • Docetaxel* / therapeutic use
  • Drug Synergism
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Poly(ADP-ribose) Polymerases / metabolism
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Taxoids / pharmacology
  • Taxoids / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Diarylheptanoids
  • Docetaxel
  • bisdemethoxycurcumin
  • Antineoplastic Agents
  • Cyclin B1
  • Curcumin
  • Taxoids
  • Proto-Oncogene Proteins c-bcl-2
  • Poly(ADP-ribose) Polymerases
  • CDC2 Protein Kinase