Phytochemicals As Chemosensitizers: From Molecular Mechanism to Clinical Significance
Publication: Antioxidants & Redox Signaling
Volume 18, Issue Number 11
Abstract
This review provides an overview of the clinical relevance of chemosensitization, giving special reference to the phenolic phytochemicals, curcumin, genistein, epigallocatechin gallate, quercetin, emodin, and resveratrol, which are potential candidates due to their ability to regulate multiple survival pathways without inducing toxicity. We also give a brief summary of all the clinical trials related to the important phytochemicals that emerge as chemosensitizers. The mode of action of these phytochemicals in regulating the key players of the death receptor pathway and multidrug resistance proteins is also abridged. Rigorous efforts in identifying novel chemosensitizers and unraveling their molecular mechanism have resulted in some of the promising candidates such as curcumin, genistein, and polyphenon E, which have gone into clinical trials. Even though considerable research has been conducted in identifying the salient molecular players either contributing to drug efflux or inhibiting DNA repair and apoptosis, both of which ultimately lead to the development of chemoresistance, the interdependence of the molecular pathways leading to chemoresistance is still the impeding factor in the success of chemotherapy. Even though clinical trials are going on to evaluate the chemosensitizing efficacy of phytochemicals such as curcumin, genistein, and polyphenon E, recent results indicate that more intense study is required to confirm their clinical efficacy. Current reports also warrant intense investigation about the use of more phytochemicals such as quercetin, emodin, and resveratrol as chemosensitizers, as all of them have been shown to modulate one or more of the key regulators of chemoresistance. Antioxid. Redox Signal. 18, 1307–1348.
Abstract
I. Introduction
II. Chemotherapeutic Agents and Their Limitations
III. Molecular Pathways That Influence Chemosensitivity
A. Involvement of intrinsic pathway in chemoresistance
B. Extrinsic pathway and chemoresistance
C. ROS signaling and nuclear factor erythroid 2-related factor 2 in chemoresistance
D. Signaling cross-talks in chemoresistance
E. Inhibitor-of-apoptosis proteins as regulators of chemoresistance
F. Role of ubiquitin-proteasome pathway in chemoresistance
G. Involvement of autophagy in chemoresistance
H. MDR and chemoresistance
IV. Chemosensitizers: Potential Candidates Under Evaluation
V. Phytochemicals Sensitizing Tumor Cells to Conventional Chemotherapeutic Drugs
A. Curcumin
B. Genistein
C. Epigallocatechin gallate
D. Quercetin
E. Emodin
F. Resveratrol
VI. The Relevance and Importance of the Phytochemicals Addressed: Clinical Trials
VII. Reduced Bioavailability of Phytochemicals As a Drawback for Their Clinical Use
VIII. Phytochemicals As Radiosensitizers
IX. Some Important Facts To Be Borne in Mind While Using Phytochemicals As Chemosensitizers
X. Conclusions
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Published In
Antioxidants & Redox Signaling
Volume 18 • Issue Number 11 • April 10, 2013
Pages: 1307 - 1348
PubMed: 22871022
Copyright
Copyright 2013, Mary Ann Liebert, Inc.
History
Published in print: April 10, 2013
Published online: 25 February 2013
Published ahead of print: 9 October 2012
Published ahead of production: 7 August 2012
Accepted: 7 August 2012
Revision received: 7 August 2012
Received: 18 February 2012
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