Annurca apple polyphenol extract selectively kills MDA-MB-231 cells through ROS generation, sustained JNK activation...

Area of Science:

• * Nutraceuticals and Cancer Therapeutics
• * Molecular Biology and Cell Signaling
• * Phytochemistry and Drug Discovery

Background:

• * Polyphenols are extensively studied nutraceuticals with therapeutic potential for various diseases, including cancer.
• * Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to limited targeted treatment options.
• * Annurca apple polyphenol extract (APE) has not been previously investigated for its anticancer properties.

Purpose of the Study:

• * To investigate the antitumor activities of Annurca apple polyphenol extract (APE) in MDA-MB-231 triple-negative breast cancer cells.
• * To elucidate the underlying molecular mechanisms responsible for APE's anticancer effects.
• * To explore APE as a potential therapeutic agent for triple-negative breast cancer.

Main Methods:

• * Cell viability assays and cell cycle analysis were performed on MDA-MB-231 cells treated with APE.
• * Reactive oxygen species (ROS) generation was measured, and the role of antioxidants like N-acetylcysteine (NAC) was assessed.
• * Western blotting was used to analyze the phosphorylation status of key signaling proteins (JNK/c-Jun, AKT) and the expression of oncoproteins (Dusp-1, NF-kB, c-myc, β-catenin).

Main Results:

• * APE selectively inhibited MDA-MB-231 cell viability, inducing G2/M phase arrest with altered expression of cell cycle regulators (p27, p21, phospho-cdc25C).
• * APE promoted ROS generation in cancer cells, which was identified as a critical mediator of its antitumor activity, as confirmed by NAC treatment.
• * APE induced JNK/c-Jun phosphorylation and inhibited AKT activation, alongside downregulating oncoproteins like NF-kB, c-myc, and β-catenin, with these effects being ROS-dependent.

Conclusions:

• * Annurca apple polyphenol extract (APE) exhibits significant antitumor activity against triple-negative breast cancer cells.
• * The anticancer effects of APE are primarily mediated by ROS generation, leading to cell cycle arrest, apoptosis, and inhibition of key survival pathways.
• * APE demonstrates potential as a promising natural compound for the development of novel therapeutic strategies against triple-negative breast cancer.