The translational potential of epigenetic modulatory bioactive phytochemicals as adjuvant therapy against cancer

In preclinical studies, bioactive phytochemicals have shown enormous potential therapeutic efficacy against various human malignancies. These natural compounds have been shown to possess an inherent potential to alter the molecular signaling pathways and epigenetic modulatory activity involved in multiple physiological functions. Recently, epigenetic therapy has emerged as an important therapeutic modality due to the reversible nature of epigenetic alterations. To date, epigenetic modulatory compounds, for example, DNA methyltransferase inhibitors 5-azacytidine and 5'-deoxyazacytidine, as well as histone deacetylase inhibitors Vorinostat, Romidepsin, and Belinostat (PXD101), have been clinically approved by the FDA for the treatment of patients of leukemia and myelodysplastic syndrome. However, these synthetic epigenetic inhibitors are not as effective against many of the solid tumors. Therefore, the epigenetic modulatory phytochemicals provide new hope for improving the treatment modality as neoadjuvant and adjuvant therapy. It has been established that targeting more than one protein in the transformed cells simultaneously, that is, the multi-targeted therapeutic approach, might invoke a better therapeutic response. Therefore, here, we are compiling diverse evidences of the translational potential of novel combinatorial approaches utilizing the epigenetic modulatory phytochemicals with available therapeutics in the course of cancer treatment.