Centchroman (CC) or
Ormeloxifene has been shown to induce apoptosis and cell cycle arrest in various types of
cancer cells. This has, however, not been addressed for
endometrial cancer cells where its (CC) mechanism of action remains unclear. This study focuses on the basis of antineoplasticity of CC by blocking the targets involved in the cell cycle, survival and apoptosis in
endometrial cancer cells. Ishikawa Human
Endometrial Cancer Cells were cultured under
estrogen deprived medium, exposed to CC and analyzed for proliferation and apoptosis. Additionally, we also analyzed oxidative stress induced by CC. Cell viability studies confirmed the IC50 of CC in Ishikawa cells to be 20 µM after 48 h treatment. CC arrests the cells in G0/G1 phase through
cyclin D1 and
cyclin E mediated pathways.
Phosphatidylserine externalization, nuclear morphology changes, DNA fragmentation, PARP cleavage, and alteration of Bcl-2 family
protein expression clearly suggest ongoing apoptosis in the CC treated cells. Activation of
caspase 3 & 9, up-regulation of AIF and inhibition of apoptosis by
z-VAD-fmk clearly explains the participation of the intrinsic pathway of programmed cell death. Further, the increase of ROS, loss of
MMP, inhibition of
antioxidant (MnSOD, Cu/Zn-SOD and GST) and inhibition of apoptosis with
L-NAC suggests CC induced oxidative stress leading to apoptosis via mitochondria mediated pathway. Therefore, CC could be a potential therapeutic agent for the treatment of
Endometrial Cancer adjunct to its utility as a
contraceptive and an anti-
breast cancer agent.