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Related Experiment Videos

Vitamin D receptor: a potential target for intervention.

Candace S Johnson1, Pamela A Hershberger, Ronald J Bernardi

  • 1Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. johnsoncs@msx.upmc.edu

Urology
|September 17, 2002
PubMed
Summary

Low vitamin D (calcitriol) levels may increase prostate cancer risk. Calcitriol shows significant antitumor effects by inducing cell cycle arrest and apoptosis, with potential clinical applications in cancer therapy.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Epidemiologic studies link low vitamin D (calcitriol) exposure to increased prostate cancer risk.
  • Calcitriol is crucial for mineral metabolism and exhibits potent antiproliferative effects on various cancer cells.
  • Vitamin D receptor (VDR) signaling is implicated in cancer development and progression.

Purpose of the Study:

  • To investigate the antitumor activity of calcitriol in prostate and squamous cell carcinoma models.
  • To elucidate the molecular mechanisms underlying calcitriol's anti-cancer effects.
  • To evaluate the safety and feasibility of high-dose calcitriol in clinical trials, alone and in combination with other agents.

Main Methods:

  • In vitro and in vivo studies using prostate and squamous cell carcinoma models.

Related Experiment Videos

  • Analysis of cell cycle regulation (G0/G1 arrest) and apoptosis markers (PARP cleavage, Bax/Bcl-2 ratio, MAPK, Akt, caspases).
  • Phase 1 and 2 clinical trials assessing calcitriol efficacy, safety, maximum tolerated dose (MTD), and hypercalcemia management.

    • Main Results:

    • Calcitriol demonstrated significant antitumor activity, inducing G0/G1 cell cycle arrest and apoptosis in preclinical models.
    • Calcitriol modulated key proteins involved in cell cycle control (p21, p27) and apoptosis.
    • Dexamethasone potentiated calcitriol's antitumor effects and mitigated hypercalcemia.
    • Phase 1/2 trials indicated high-dose calcitriol is feasible on an intermittent schedule, with dexamethasone or paclitaxel potentially managing hypercalcemia.

    Conclusions:

    • Calcitriol possesses significant antitumor properties against prostate and squamous cell carcinomas through cell cycle arrest and apoptosis induction.
    • Calcitriol, particularly in combination with dexamethasone or paclitaxel, shows promise for clinical application in cancer therapy.
    • Further studies are warranted to define the MTD and optimize treatment regimens for calcitriol in cancer patients.