Reprogramming Tumorigenesis and the Tumor Microenvironment with Flavokawains

Area of Science:

• Phytochemistry
• Pharmacology
• Oncology

Background:

• Cancer poses a significant global health burden, driving research into novel therapeutics.
• Naturally derived compounds, particularly phytochemicals, are increasingly explored for their therapeutic potential and reduced toxicity.
• Flavokawains, a subclass of chalcones, exhibit diverse pharmacological activities, including potent anticancer effects.

Purpose of the Study:

• To review and evaluate preclinical evidence on the anticancer mechanisms of flavokawains.
• To explore the impact of flavokawains on cancer cell proliferation, apoptosis, cell cycle, and key molecular pathways.
• To assess the effects of flavokawains on the tumor microenvironment, including angiogenesis, epithelial-mesenchymal transition, and cancer stem cells.

Main Methods:

• Systematic review of preclinical studies on flavokawains.
• Analysis of in vitro and in vivo cancer models.
• Evaluation of molecular pathway modulation and tumor microenvironment interactions.

Main Results:

• Flavokawains inhibit cancer cell proliferation, induce apoptosis, and disrupt cell-cycle progression.
• These compounds modulate critical oncogenic pathways such as PI3K/Akt/mTOR, NF-κB, and ERK/JNK/MAPK.
• Flavokawains suppress angiogenesis (VEGF, Ang-1), epithelial-mesenchymal transition (E-cadherin, vimentin, Snail1), MMPs, and cancer stem cell niches.

Conclusions:

• Flavokawains demonstrate multifaceted anticancer mechanisms with selective cytotoxicity.
• Their ability to target multiple pathways and the tumor microenvironment makes them promising candidates.
• Further research is warranted to establish their therapeutic index for potential use as adjuncts or alternatives to conventional chemotherapy.