Therapeutic Paradigm Underscoring Glucosinolate Sulforaphane in Chemo- and Radiosensitization of Cancer: Preclinical and Clinical Perspective

Abstract

Fruits and vegetables harbor innocuous bioactive compounds which after absorption and distribution tend to have an effect on general defense mechanism of the body including cancer prevention and therapeutic effects. Emerging knowledge from clinical and laboratory studies reveal an important insight regarding their mechanism of action orchestrating therapeutic paradigm with conventional cancer treatment modalities to enhance the curative index of cancer treatment. However, unlike conventional cancer therapeutics, natural bioactive compounds rarely develop resistance undermining their chemopreventive actions. One such bioactive natural compound – sulforaphane, a cognate isothiocyanate limited mostly to vegetables of Brassica family and enriched in broccoli – is considered a promising chemopreventive agent against cancer. Sulforaphane is released from hydrolysis of glucoraphanin isothiocyanate by action of myrosinase enzyme which is also found localized inside vegetal tissues. Overwhelming evidence points to sulforaphane’s multitargeted actions operationally targeting core cell survival signaling pathways in tumor cells and enzyme induction mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated transcriptions of genes encoding carcinogen detoxification, antioxidant enzymes, and other effects including reversal of resistance and reduction in the systemic toxicity of drug. This chapter presents a broad perspective on the role of sulforaphane in augmenting multimodal cancer therapy including putative mechanism complementing the efficacy of chemo- and radiotherapy with presumptive notion of its future use in clinics in fight against cancer and patient’s benefit. Clinical trials have also been reviewed to ensure clinical safety and efficacy of sulforaphane in patients diagnosed with cancer.