Chemotherapeutic Potential of Novel Selenium (Se) Analog of Histone Deacetylase (HDAC) Inhibitor, Suberoylanilide Hydroxamic Acid (SAHA) in Experimental Colorectal Cancer

Abstract

Colorectal cancer (CRC), one of the leading causes of cancer related deaths worldwide is an outcome of both genetic and epigenetic changes in colonic epithelia leading to the formation of adenocarcinomas. Histone deacetylases (HDACs) through their key roles in regulation of cellular processes, are associated with the development and progression of cancer. Thus, in this regard, HDAC inhibitors have become promising therapeutic targets. These inhibitors induce cell cycle arrest, differentiation, autophagy and apoptotic cell death by inhibiting multiple signaling pathways. Suberoylanilide hydroxamic acid (SAHA), a second generation HDAC inhibitor has been approved by US‐FDA for the treatment of cutaneous T‐Cell lymphoma, however its anti‐cancerous effects against colorectal cancer is still unknown. Also, essential dietary element Selenium (Se) has been found to have an important role in CRC prevention via modulating redox sensitive molecular pathways. Therefore, the present study aimed to explore the anti‐tumorigenic role of SAHA and its Se analog namely, SelSA‐1 (25 mg/kg) in DMH induced experimental colon cancer model in Balb/c mice. The toxicity studies and pharmacokinetic characterization of SelSA‐1 exhibited better tolerance, absorption and elimination rate than SAHA. Further, histological and morphological analyses showed that SelSA‐1 has better/comparable chemotherapeutic potential compared to SAHA at lower doses than SAHA. Further, the positive redox modulatory effects of SelSA‐1 and SAHA in CRC associated oxidative stress were also noteworthy, projecting the plausible use of similar analogs as compounds of choice for cancer treatments based on their safety profiles, efficacy and specificity in terms of chemotherapeutic potential.Support or Funding InformationDepartment of Science and Technology (DST), Govt. of India, New Delhi; University Grant Commission (UGC), Govt. of India, New DelhiThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.