Curdepsidone A Induces Intrinsic Apoptosis and Inhibits Protective Autophagy via the ROS/PI3K/AKT Signaling Pathway...

Area of Science:

• Oncology
• Pharmacology
• Cell Biology

Background:

• Cervical cancer is a significant global health issue, ranking as the fourth most common malignancy in women.
• In 2020, over 600,000 women were diagnosed with cervical cancer, resulting in over 300,000 deaths worldwide.
• Curdepsidone A, a depsidone derivative from *Curvularia* sp. IFB-Z10, shows potential for therapeutic intervention.

Purpose of the Study:

• To elucidate the anti-tumor mechanism of Curdepsidone A in cervical cancer.
• To investigate the effects of Curdepsidone A on cell cycle, apoptosis, autophagy, and key signaling pathways in HeLa cells.

Main Methods:

• Revision of Curdepsidone A's molecular structure.
• Treatment of HeLa cells with Curdepsidone A to assess its impact on cell cycle progression (G0/G1 arrest).
• Evaluation of apoptosis induction via the mitochondrial pathway.
• Analysis of autophagy flux, reactive oxygen species (ROS) levels, and the PI3K/AKT signaling pathway.
• Pharmacological modulation using a PI3K inhibitor (LY294002), a PI3K agonist (IGF-1), and an ROS scavenger (NAC).

Main Results:

• Curdepsidone A induced G0/G1 phase cell cycle arrest and triggered apoptosis through a mitochondrial pathway in HeLa cells.
• The compound inhibited autophagic flux and suppressed the PI3K/AKT pathway, leading to increased ROS accumulation.
• Inhibition of PI3K enhanced Curdepsidone A-induced apoptosis, while PI3K activation diminished it; ROS scavenging reduced apoptosis and pathway suppression.

Conclusions:

• Curdepsidone A effectively hinders cervical cancer cell growth by inducing cell cycle arrest and apoptosis.
• The anti-tumor effects are mediated by the inhibition of autophagy and the ROS-modulated PI3K/AKT pathway.
• Curdepsidone A presents a promising molecular basis for development as a novel chemotherapy agent for cervical cancer.