Scientists have found a promising compound that kills prostate cancer cells by compromising their ability to withstand environmental stress.
The study led by researchers at Sanford-Burnham Medical Research Institute uncovered the mechanism behind the anticancer compound called SMIP004. For prostate cancer patients,one treatment option is castration the chemical or surgical removal of the testes which reduces the production of the male sex hormone testosterone.
This strategy works because prostate cancer cells,at least initially,depend on testosterone for their growth and survival. But many patients eventually develop castration-resistant prostate cancer,in which the cancer cells adapt and become insensitive to hormone deprivation therapy.
“For advanced prostate cancer castration-resistant prostate cancer in particular – when the cancer recurs,the only therapy is Taxol,which will prolong life for only a couple of months,” said senior study author Dieter Wolf,director of the National Cancer Institute-designated Cancer Center proteomics facility at Sanford-Burnham.
“There’s good potential that our compound could become a novel,much-needed therapy for castration-resistant prostate cancer,” Wolf said. In a previous study,Wolf and his team identified SMIP004 as a promising anticancer agent when they screened for compounds that specifically kill prostate cancer cells while sparing normal cells. But until now,exactly how SMIP004 works was unknown.
In the new study,the researchers found that SMIP004 causes cancer cells to die by interfering with the functioning of mitochondria – structures within cells that are responsible for generating energy and controlling cell growth and death.
In a process known as oxidative stress,harmful molecules called reactive oxygen species (ROS) built up within mitochondria,causing the cells to stop replicating and to start dying.
Wolf and his team pinpointed the exact molecular signalling pathways underlying SMIP004’s effects and identified ROS-mediated activation of the unfolded protein response as the trigger of cancer-cell death.
Through one of the newly identified pathways triggered by oxidative stress,SMIP004 caused a decrease in the number of androgen receptors – proteins within prostate cancer cells that are activated by testosterone. Moreover,the researchers found that SMIP004 strongly inhibited the growth of prostate and breast cancer in mice,underscoring the compound’s potential value in treating a range of cancers. The study was published in journal Oncotarget.