Title:Impediment of Cancer by Dietary Plant-derived Alkaloids Through Oxidative
Stress: Implications of PI3K/AKT Pathway in Apoptosis, Autophagy,
and Ferroptosis
Volume: 23
Issue: 10
Author(s): Prasath Manogaran*, Narasimha Murthy Beeraka, Raja Singh Paulraj, Perumal Sathiyachandran and Mahadevaswamy Thammaiappa
Affiliation:
- Department of Biotechnology, Bharathiar University, Coimbatore-541046, India
Keywords:
Alkaloids, Dietary phytochemicals, PI3K/AKT, ROS, Chemotherapy, Anti-cancer agents.
Abstract: The adverse toxicities and stemness are two major factors that constrained the usage of
therapeutic strategies to target several cancer types. Previous studies explored the efficacy of
PI3K/mTOR inhibitors, pan-PI3K inhibitors, and isoform-specific inhibitors against several cancer
types, and many of them are currently in clinical trials. The current review described the efficacy of
alkaloids derived from dietary plant sources in developing a new anti-cancer to reduce the prevalence
of cancer through the modulation of apoptosis, autophagy, and ferroptosis. We have substantially
collected the information pertinent to several intracellular pathways, including PI3K signaling,
apoptosis, ferroptosis, and autophagy in modulating cancer progression mediated by the plantderived
alkaloids such as daurisoline, dauricine, vasicine, vasicinone, 2-Acetyl-benzylamine, nuciferine,
liensinine, gramine, and berbamine. These alkaloids exhibit significant anti-cancer potential
to inhibit cancer cells by enhancing the intracellular ROS level and modulation of several signaling
pathways, mainly through the PI3K/AKT pathway. These alkaloids can modulate chemotherapeutic
agents' efficacy in various cancer cells, both in vitro and in vivo models. Overall the futures
for the continued use of alkaloids from natural sources against cancer have to be extended,
with the implementation of significant enhancements in the chemistry of these alkaloids for targeted
delivery. In this review, we have selected major bioactive alkaloids of dietary and medicinal plants
origin and discussed the anti-cancer and combinatorial therapeutic implications of these compounds
with several FDA-approved drugs against various cancer cells.
