Pro-oxidative phytoagents induce autophagy in tumors: villain or benefactor in cancer treatment?

Cancer remains one of the major causes of human death worldwide, especially with recurring, metastatic, or drug-resistant tumors. As botanical preparations have been used for treating various human diseases throughout history, plant-derived chemicals (phytoagents) thus become an important resource for discovery of novel therapeutic agent for cancer treatment. Increasing evidence showed transformed state of cancer confers an altered redox condition that makes cancer cells vulnerable to treatments which augment oxidative stress in the cells. Therefore, studies have shed light on the pro-oxidant effects of some phytoagents pose selective cytotoxicity on cancer cells. In response to oxidative stress stimulated by cytotoxic agents, autophagy is a common cellular process induced to recycle damaged proteins/organelles as a survival mechanism in cells or to trigger type II programmed cell death when the damage is irreparable. In this review, we enumerated several phytoagents reported to induce oxidative stress that inhibit tumor growth. In most cases, anticancer activities of these pro-oxidative phytoagents involve autophagy that provokes apoptosis-independent program, complementing apoptotic cell death to enhance the killing effect. However, some phytoagents induce oxidative stress that stimulates protective autophagy, attenuating their anticancer effect. Therefore, the possible mechanisms on how phytoagent-induced autophagy decides treated cell fate are briefly discussed in this review.