Shikonin selectively induces apoptosis in human prostate cancer cells through the endoplasmic reticulum stress and mitochondrial apoptotic pathway

• DOI: 10.1186/s12929-015-0127-1
• Publication Date: 2015-04-02T14:23:50Z
• Authors: Rishi Kumar Gara; Vikas Kumar Sriva...; Shivali Duggal; Jaspreet Kaur Bagga; MLB Bhatt; Sabyasachi Sanyal; Durga Prasad Mishra
• Keywords: Biochemistry, medical; Male; Membrane Potential, Mitochondrial; 0303 health sciences; Endocrinology, Diabetes and Metabolism; Research; Clinical Biochemistry; Prostatic Neoplasms; Antineoplastic Agents; Apoptosis; Cell Biology; Endoplasmic Reticulum Stress; Mitochondria; 3. Good health; 03 medical and health sciences; Cell Line, Tumor; Humans; Pharmacology (medical); Molecular Biology; Cell Proliferation; Naphthoquinones

Despite the recent progress in screening and therapy, a majority of prostate cancer cases eventually attain hormone refractory chemo-resistant attributes. Conventional chemotherapeutic strategies are effective at very high doses for only palliative management these cancers. Therefore chemo-sensitization cells could be promising strategy increasing efficacy conventional agents patients. Recent studies have indicated that chemo-preventive natural restore pro-apoptotic protein expression induce endoplasmic reticulum stress (ER stress) leading to inhibition cellular proliferation activation mitochondrial apoptosis cells. reprogramming ER stress-mitochondrial dependent potential approach chemoresistant We aimed study effects naphthoquinone Shikonin human The results induces through dual induction dysfunction. induced ROS generation activated calpain activity. Moreover, addition antioxidants attenuated effects. also apoptotic pathway mediated enhanced Bax Bcl-2, disruption membrane (MMP) followed by caspase-9, caspase-3, PARP cleavage. suggest shikonin useful therapeutic cancers due its modulation pathways.