Underlying Anticancer Mechanisms and Synergistic Combinations of Phytochemicals with Cancer Chemotherapeutics: Potential Benefits and Risks

Cancer therapies are associated with various challenges including the emergence of multidrug resistant tumors, toxicological issues, severe side effects, and economic burden. To counteract these effects, natural products as substitutes and adjuvant therapies have received considerable attention owing to their safety, efficacy, and economic aspects. Various preclinical and clinical studies revealed that natural products and their combinations with chemotherapeutics mediate their anticancer effects via modulation of various signaling pathways implicated in promoting apoptosis, inhibiting excessive cellular proliferation, and mobilizing the immune system. Several lead phytochemicals including curcumin, resveratrol, quercetin, and cannabinoids synergistically act with cancer chemotherapeutics reducing cell proliferation and inducing apoptosis and cell cycle arrest. However, clinical studies on the subject matter are limited and need further extensive studies. It has been observed that patients undergoing chemotherapy use alternative therapies to ameliorate the symptoms associated with the use of chemotherapeutic agents. Nevertheless, some of the patients inform their physicians regarding herbal medicine during chemotherapy while others do not, and even most of the patients do not know the composition of herbal medicine they consume during chemotherapy. Herbal interactions with chemotherapeutics are associated with both beneficial and harmful aspects, but the beneficial aspect overweighs the harmful ones in terms of controlling the symptoms associated with the chemotherapy. Nonetheless, a large number of herbal medicines have been demonstrated to have synergistic effect with chemotherapy and alleviate the side effects of chemotherapeutic agents. The concomitant use of the majority of herbal medicines with chemotherapy has been demonstrated to be beneficial in multiple malignant tumors like cancer of blood, lungs, kidneys, liver, skin, and gastrointestinal tract. However, herbal medicines which possess positive interaction and improve the quality of life of patients should be sorted out and integrated with the chemotherapy. There should be a quality control system for the appraisal of herbal medicine, and there should also be an appropriate system of patient-doctor communication to counsel the patients regarding the beneficial and deleterious effects of the herbal medicine in combination with chemotherapy.