Cancer is a multifaceted disease. Our deepened knowledge about genetic and biological
mechanisms of cancer cells presents an opportunity to explore the inter-individual differences in the
body’s ability to metabolize and respond to different nutrients. It is becoming progressively more understandable
that the deregulation of several signaling pathways and the alterations in apoptotic response
are some of the major determinants that underpin carcinogenesis. Tumor necrosis factor-Related
Apoptosis-Inducing Ligand (TRAIL)-mediated signaling has gained a remarkable appreciation because
of its ability to selectively induce apoptosis in cancer cells leaving normal cells intact. However, technological
advances have started to shed light on underlying mechanisms of resistance against TRAILinduced
apoptosis in cancer cells. The impairment of TRAIL-mediated apoptosis includes various factors
ranging from the loss or down regulation of TRAIL receptors or pro-apoptotic proteins to the up
regulation of anti-apoptotic proteins. Intriguingly to mention that there is an ever-increasing number of
natural herbal extracts (phytometabolites), which have been explored to date for their potential action in
restoring apoptosis TRAIL-mediated in cancer cells. In this review, we will highlight the progress in
understanding the mechanisms opted by phenolic compounds in overcoming TRAIL resistance.
Keywords: Cancer, Herbal extracts, TRAIL, Apoptosis, Caspases.
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