Tuesday, January 31, 2012. In the journal BMC Medicine on January 26, 2012, Professor Sanjay K. Srivastava and Prabodh K. Kandala of Texas Tech University Health Sciences Center in Amarillo report the discovery of a mechanism for diindolylmethane (DIM), an active metabolite of indole-3-carbinol found in cruciferous vegetables, to induce programmed cell death (apoptosis) in cultured ovarian cancer cells.
Previous research uncovered an inhibitory effect for DIM on ovarian cancer cell growth, yet the mechanism involved remained unknown. The current study explored the effects of DIM in several ovarian cancer lines. Drs Srivastava and Kandala found that DIM induces apoptosis, and that it exerts its effects by blocking the production and activation of signal transducer and activator of transcription 3 (STAT3), a transcription factor that is associated with the growth and survival of cells which is over-expressed in cases of resistance to the chemotherapy cisplatin. DIM also reduced the proinflammatory cytokine interleukin-6 in ovarian tumor cells, and inhibited cell invasion and angiogenesis via suppression of hypoxia-inducible factor 1-alpha and vascular epithelial growth factor.
In further experimentation, the duo pretreated ovarian cancer cells with DIM, followed by the administration of cisplatin for 24 hours. The combination of DIM and cisplatin resulted in a 50 to 70 percent reduction in cell survival, in contrast with a 28 percent reduction in cells treated with cisplatin alone. Furthermore, mice treated with DIM alone or DIM and cisplatin experienced retarded growth of implanted ovarian tumors compared to untreated mice or animals that received cisplatin alone. “Our results demonstrate that DIM suppresses the growth of ovarian cancer cells and potentiates the effect of cisplatin in vitro and in vivo by targeting STAT3 signaling without being toxic to normal ovarian cells,” the authors write. “To the best of our knowledge, this is the first report demonstrating STAT3 as a target of DIM.”
“Cisplatin is very toxic and has severe side effects,” Drs Srivastava and Kandala explained. “If co-treatment with DIM means that a low dose of cisplatin can be given to patients without the loss of therapeutic effect, but with reduced side effects, it would represent a significant breakthrough in clinical practice.”