Abstract
Continuous accumulation of ROS maintains oxidative stress in tumor microenvironment and is implicated in hyperactivation of signaling pathways that promote cell proliferation, survival, and metabolic adaptations to cancer. Antioxidants are supposed to interfere with tumor microenvironment. Plant-derived flavonoids and curcuminoids are considered as promising therapeutic molecules due to least side effects. Anticarcinogenic activity of various herbal antioxidants is widely reported. However, supports from preclinical studies and clinical trials are insufficient. Critical insight in signaling pathways leading to cancer progression and regulation of specific targets by herbal antioxidants in preclinical studies is a prerequisite to overcome the lacuna in its successful translation into therapeutical medicine. Most of the studies are limited to in vitro tests, revealing the action at cellular level. However, the natural antioxidants need validation at the level of cancer regression and better survival of laboratory animals. This review will focus on various signaling pathways leading to cancer progression and their interception by herbal antioxidants with a greater emphasis on the antioxidants being most widely validated in vitro and in animal models. These drugs are at the preliminary stage of testing as supplementary or alternative drugs in patients. The review will provide insight to overcome the failures in clinical practice and scope for development of novel anticancer drugs.