A Comprehensive Review on Necroptosis Inducing Phytochemicals for Cancer Therapy: Preclinical Evidence

Area of Science:

• Oncology
• Cell Death Research
• Molecular Biology

Background:

• Cancer cells often evade apoptosis, a key programmed cell death pathway, contributing to therapeutic resistance.
• Necroptosis, a regulated form of necrosis, is emerging as a crucial alternative to overcome apoptosis evasion and enhance treatment efficacy.
• Key mediators like RIPK1, RIPK3, and MLKL orchestrate necroptosis, influencing inflammatory and immune responses, though its role in cancer is complex, potentially acting as both a tumor suppressor and metastasis promoter.

Purpose of the Study:

• To review the mechanisms and roles of necroptosis in cancer.
• To explore the potential of targeting necroptosis to combat apoptosis resistance in cancer therapy.
• To summarize current data on the connection between necroptosis and cancer, with a focus on phytochemicals.

Main Methods:

• A comprehensive literature search was conducted across five major databases.
• 314 relevant articles were meticulously selected and analyzed.
• The review synthesizes data on necroptosis-inducing phytochemicals and their molecular mechanisms.

Main Results:

• Phytochemicals, including phenolics, alkaloids, and terpenoids, show potential in cancer therapy by inducing oxidative stress and activating RIPK1/RIPK3-dependent necroptotic signaling.
• These bioactive compounds offer a promising approach to target necroptosis pathways for oncological therapies.
• The review consolidates evidence for phytochemical-induced necroptosis, highlighting its anti-cancer potential.

Conclusions:

• Targeting necroptosis presents an innovative strategy to overcome cancer's resistance to apoptosis.
• Phytochemicals are identified as promising agents capable of inducing necroptosis and exhibiting anti-cancer effects.
• Further research is needed to translate these findings into clinical applications, addressing existing barriers.