c-Jun N-terminal Kinase (JNK), p38, and Caspases: Promising Therapeutic Targets for the Regulation of Apoptosis in Cancer Cells by Phytochemicals

Abstract

Abstract: Carcinogenesis is a process in which uncontrolled cell proliferation forms preneoplastic nodules which precede the appearance of cancer. In normal cells, growth and proliferation are regulated by certain growth and hormonal stimulation, while mutational alterations in these signals render the cells independent and resistant to these signals. In cancer, the critical homeostatic balance between cell growth and apoptosis is lost and the cells continue to survive beyond their normal life span. The activation of c-Jun N-terminal kinase (JNK), p38 and caspases are involved in potential proapoptotic signaling pathways. JNK, p38 MAPK pathway and caspases play a crucial role in the control of apoptosis in response to stress. The most recent and up-to-date literature was evaluated in this study, which describes the role of JNK, p38 MAPK pathway and caspases as therapeutic target in cancer. Chemotherapy uses drugs that are cytotoxic to highly proliferating tumor cells but also kills the non-tumor rapidly proliferating cells in the hair, skin and gastrointestinal tract epithelium, thereby accounting the side effects of these types of treatments. Recently, chemopreventive modalities derived from phytoconstituents present in plants provide a broad-spectrum strategy to overcome the incidence of cancer. Non-toxic, safe and affordable bioavailabilities of chemopreventive agents provide credence support in the field of cancer research compared to conventional therapies that cause serious consequences. Chemoprevention envisages the basic mechanisms like modulating the activity of xenobiotic-metabolizing enzymes, induction of apoptosis, immune system activation, suppressing angiogenesis and the formation of metastasis, antioxidant and anti-inflammatory properties. The present review highlighted the role of phytoconstituents derived from food, vegetables and medicinal plants in the induction of apoptosis in cancer cells, which in turn is mediated by the activation of JNK, p38 MAPK pathways, and caspases.