Progesterone-calcitriol combination enhanced cytotoxicity of cisplatin in ovarian and endometrial cancer cells in vitro

Ana Paucarmayta, Hannah Taitz, Latoya McGlorthan, Yovanni Casablanca, G. Larry Maxwell, Kathleen M. Darcy, Viqar Syed*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Initially, patients that respond to cisplatin (DDP) treatment later relapse and develop chemoresistance. Agents that enhance DDP effectiveness will have a significant impact on cancer treatment. We have shown pronounced inhibitory effects of the progesterone-calcitriol combination on endometrial and ovarian cancer cell growth. Here, we examined whether and how progesterone-calcitriol combination potentiates DDP anti-tumor effects in cancer cells. Ovarian and endometrial cancer cells treated with various concentrations of DDP showed a concentration-dependent decrease in cell proliferation. Concurrent treatment of cells with DDP and progesterone-calcitriol ombination potentiated anticancer effects of DDP compared to DDP-calcitriol, or DDP-progesterone treated groups. The anticancer effects were mediated by increased caspase-3, BAX, and decreased BCL2 and PARP-1 expression in DDP and progesterone-calcitriol combination-treated cells. Stimulation of the PI3K/AKT and MAPK/ERK pathways seen in cancer cells was reduced in DDP-progesterone-calcitriol treated cells. Pretreatment of cells with specific inhibitors further diminished AKT and ERK expression. Furthermore, progesterone-calcitriol potentiated the anti-growth effects of DDP on cancer cells by attenuating the expression of SMAD2/3, multidrug resistance protein- 1 (MDR-1), and ABC transporters (ABCG1, and ABCG2), thereby impeding the effiux of chemo drugs from cancer cells. These results suggest a potential clinical benefit of progesterone-calcitriol combination therapy when used in combination with DDP.

Original languageEnglish
Article number73
Issue number4
StatePublished - 1 Apr 2020
Externally publishedYes


  • ABC transporters
  • Cisplatin
  • Gynecological cancer
  • Multidrug resistance protein-1
  • SMAD2/3


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