Abstract
Cancer is a multifaceted molecular disorder that is modulated by a combination of genetic, metabolic and signal transduction aberrations, which severely impair the normal homeostasis of cell growth and death. Accumulating findings highlight the fact that different genetic alterations, such as mutations in tumor suppressor genes, might be related to distinct and differential sensitivity to targeted therapies. It is becoming increasingly apparent that a multipronged approach that addresses genetic milieu (alterations in upstream and/or parallel pathways) eventually determines the response of individual tumors to therapy. Cancerous cells often acquire the ability to evade death by attenuating cell death pathways that normally function to eliminate damaged and harmful cells. Therefore impaired cell death nanomachinery and withdrawal of death receptors from cell surface are some of major determinants for the development of chemotherapeutic resistance encountered during treatment. It is therefore essential to emphasize underlying factors which predispose cells to refractoriness against TRAIL mediated cell death pathway and the relevant regulatory components involved. We bring to limelight the strategies to re-sensitize TRAIL resistant cells via vitamins to induce apoptosis.
Highlights
TRAIL plays an imperative role in host immunosurveillance in opposition to tumor progression, as it triggers apoptosis of tumor cells but not normal cells, and has great therapeutic potential for cancer treatment
This review provides a summary of the impact of vitamins on mechanisms connected with enhancement of TRAIL mediated signaling together with modulation of the apoptotic (death receptor expression, FLIP, and Bcl-2 or inhibitors of apoptosis (IAP) families) as well as cell signal transduction cascades
We discuss how the field of internalization and degradation of death receptors has matured and present growing model in which membranes are occupied by fluctuating nanoscale assemblies of sphingolipids, cholesterol and proteins that can be stabilized into platforms that are important in TRAIL mediated signaling and membrane trafficking
Summary
TRAIL plays an imperative role in host immunosurveillance in opposition to tumor progression, as it triggers apoptosis of tumor cells but not normal cells, and has great therapeutic potential for cancer treatment. We give a detailed account of Vitamins which are documented to stimulate the re-establishment of death receptors on plasma membrane and re-sensitizing cancer cells to TRAIL mediated apoptosis. This review provides a summary of the impact of vitamins on mechanisms connected with enhancement of TRAIL mediated signaling together with modulation of the apoptotic (death receptor expression, FLIP, and Bcl-2 or inhibitors of apoptosis (IAP) families) as well as cell signal transduction cascades.
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