AKT/GSK-3 Pathway Targeting; Botanicals and Bioactive Compounds with Anticancer Activities

Abstract

Background: In the late 20th century, the leading role of signaling pathways in various cancers is revealed via some genome's systematic investigations. The Akt/GSK-3 signaling pathway is one of the critical signaling pathways dysregulated in numerous human cancers. The Akt cascade acts in the cancer process by regulating apoptosis, cell cycle, metabolism, and cells' longevity. The GSK-3 is downstream of Akt, which has an opposite role in cancer progression. Objective: Attending to the importance of the Akt/GSK-3 pathway in cancer progression and the positive result of natural products in cancer treatment, this research is designed to review effective herbal medicines in one of the involvement critical signal pathways of cancer for developing novel anticancer drugs. Method: Keywords "plant", "natural", "cancer", "AKT", and "GSK" were searched through the "Scopus" and "Google scholar" databases up to 30th August 2020. Papers linking to pharmacology, toxicology, and pharmaceutics were collected and discussed. Results and Conclusion: The Akt/GSK-3 signaling pathway plays a prominent role in cancer. Although the effect of GSK-3 in cancer cells is depended on the type and contents of cells, the inhibition of Akt/GSK-3 mostly is led to three primary outcomes in cancer cells, including (1) apoptotic activity and autophagy induction, (2) anti-proliferative and growth inhibitory effects, and (3) anti-metastatic and angiogenesis effects. As the tendency to use natural products increases, we gathered 64 plants or bioactive components with the anticancer activity via the Akt/GSK-3 signaling pathway. Since most of these investigations have been conducted on cell lines, these plants can be the right candidate to be evaluated in human trials.