Taken together our studies suggest that (i) Shikonin inhibits proliferation of hormone refractory prostate cancer cells through the induction of ROS, mediated activation of ER stress and intracellular Ca2+, and (ii) induction of mitochondrial apoptotic pathway mediated through the enhanced expression of Bax, disruption of the mitochondrial membrane potential, PARP cleavage and activation of caspase-9 and caspase-3. Here, CASP9 is linked to Familial prostate cancer.