Natural compounds to overcome cancer chemoresistance: toxicological and clinical issues.

INTRODUCTION: Defects in initiating or executing cell death programs are responsible for cancer chemoresistance. The growing understanding of apoptotic programs suggests that compounds simultaneously inhibiting multiple signaling pathways might provide a better therapeutic outcome than that of individual inhibitors. AREAS COVERED: Natural compounds can modulate different survival pathways, thus enhancing the therapeutic effects of anticancer treatments. This review provides an overview of the preclinical and clinical relevance of chemosensitization, giving special reference to curcumin (CUR) and sulforaphane (SFN) as agents to overcome apoptosis resistance against chemotherapy. EXPERT OPINION: Even if CUR and SFN are common dietary constituents, they are characterized by several problems still unresolved and hampering their development as anticancer drugs. For a drug to be safe, it must be devoid of toxicity, and some studies conducted to date raises concern about CUR and SFN safety. Moreover, the efficacy of a drug, alone or in association, is usually determined by randomized, placebo-controlled, double-blind clinical trials. No such trials have shown CUR and SFN to be effective so far. Thus, caution should be exercised when suggesting the use of CUR or SFN for cancer-related therapeutic purpose, especially for very early stage of malignancy, or in patients who are undergoing chemotherapy.