Phytochemicals As Chemosensitizers: From Molecular Mechanism to Clinical Significance

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.

Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells

“…However, severe toxicity and acquired drug resistance after therapy are the major problem of therapy. Plant derived natural compounds were reported to act as chemosensitizer due to their ability to regulate multiple survival pathways without inducing toxicity (Vinod et al, 2013). Phytochemicals have been used nowadays as an adjuvant therapy to overcome the limitations of cisplatin treatment (Tyagi et al, 2004;Ermakova et al, 2006;Sarkar and Li, 2006).…”

Codelivery of doxorubicin and curcumin with lipid nanoparticles results in improved efficacy of chemotherapy in liver cancer

“…[4][5][6] Compared with a multiagent combination, the combination of cytotoxic and chemosensitizing agents exhibited better performance in the intracellular microenvironment, and are thus highlighted as more effective for tumor localization and for overcoming MDR. 6,7 Despite the benefits of combination therapy, the nanoparticle (NP)-based targeted drug delivery (nanocarriers) has been designed to increase drug accumulation at tumor sites to improve permeability and retention, 8 pharmacokinetic profiles, and reduce side effects. 9,10 Therefore, the delivery of a chemotherapeutic agent and chemosensitizer using nanocarriers has been suggested as a novel and promising strategy in cancer treatment.…”

The formulation for cancer prevention & therapy

“…Resveratrol is a potential candidate due their ability to regulate multiple survival pathways without inducing toxicity [174]. The strong link between inflammation and colorectal carcinogenesis provides the rationale for using anti-inflammatory agents for chemoprevention of colorectal cancer [175].…”