Natural compounds modulate the crosstalk between apoptosis- and autophagy-regulated signaling pathways: Controlling the uncontrolled expansion of tumor cells

Due to the high number of annual cancer-related deaths, and the economic burden that this malignancy affects today's society, the study of compounds isolated from natural sources should be encouraged. Most cancers are the result of a combined effect of lifestyle, environmental factors, and genetic and hereditary components. Recent literature reveals an increase in the interest for the study of phytochemicals from traditional medicine, this being a valuable resource for modern medicine to identify novel bioactive agents with potential medicinal applications. Phytochemicals are components of traditional medicine that are showing promising application in modern medicine due to their antitumor activities. Recent studies regarding two major mechanisms underlying cancer development and regulation, apoptosis and autophagy, have shown that the signaling pathways of both these processes are significantly interconnected through various mechanisms of crosstalk. Phytochemicals are able to activate pro-autophagic and pro-apoptosis mechanisms. Understanding the molecular mechanism involved in apoptosis-autophagy relationship modulated by phytochemicals plays a key role in development of a new therapeutic strategy for cancer treatment. The purpose of this review is to outline the bioactive properties of the natural phytochemicals with validated antitumor activity, focusing particularly on their role in the regulation of apoptosis and autophagy crosstalk that triggers the uncontrolled expansion of tumor cells. Furthermore, we have also critically discussed the limitations and challenges of existing research strategies and the prospective research directions in this field.