PADINA PAVONICA ETHANOL EXTRACT TRIGGERS APOPTOSIS AND CELL CYCLE DISRUPTION THROUGH REDOX STRESS AND PI3K/AKT MODULATION IN LUNG AND BREAST CARCINOMA CELLS

Abstract

Background: Marine brown algae contain bioactive compounds with anti-cancer properties. Padina pavonica (PP), a common brown alga, remains understudied for cancer cell effects. This study evaluated the cytotoxic and molecular effects of ethanol extract versus cisplatin (CP) on human lung carcinoma (A549) and breast carcinoma (MCF‑7) cells.

Methods: The SRB test was used to determine cell toxicity by determining the IC₅₀ values. After treatment with Padina pavonica (PP) extract and cisplatin (CP), cell shape changes were observed microscopically. A FLUOstar Omega microplate reader was used to measure cellular glutathione (GSH) and total antioxidant capacity. Flow cytometry with Annexin V/PI staining and PI DNA analysis was used to assess cell death and cell cycle progression. RT-qPCR measured Bax, Bcl-2, PI3K, and AKT1 gene expression, while western blotting confirmed the protein levels. One-way ANOVA with Tukey's test was used to check for statistical significance.

Results: Padina pavonica extract reduced cell viability in a dose-dependent manner, with IC50 values of 60.73 µg/mL in A549 and 173.11 µg/mL in MCF‑7, versus 1.32 µg/mL and 1.72 µg/mL for cisplatin (CP), respectively. Morphological analysis showed cytotoxic features, including shrinkage, rounding, and detachment. PP treatment depleted intracellular glutathione (GSH) and reduced antioxidant capacity, indicating disrupted redox homeostasis; depletion was partial in A549 cells but profound in MCF‑7 cells. Flow cytometry revealed that PP induced late apoptosis in A549 cells and late apoptosis/necrosis in MCF‑7 cells, whereas CP triggered both early and late apoptosis. Cell cycle analysis showed that PP caused G1 arrest in A549 cells and sub‑G1 accumulation in MCF‑7 cells, whereas CP increased the sub‑G1 population. RT‑qPCR showed upregulation of Bax and downregulation of Bcl‑2, PI3K, and AKT1 in A549 cells, while MCF‑7 cells showed reduced Bcl‑2 and AKT1 but increased PI3K. Western blotting validated these changes at the protein level, confirming PP as a modulator of apoptotic pathways.

Conclusion: Padina pavonica extract exhibits anticancer activity by reducing cell viability, altering morphology, depleting glutathione, lowering antioxidant capacity, and disrupting redox homeostasis. These effects induce apoptosis and cell cycle arrest and modulate PI3K/AKT signaling, with stronger responses in A549 versus MCF-7 cells. Although less potent than cisplatin, PP extract impaired survival pathways through layered mechanisms. These findings highlight the potential of marine brown algae as anticancer agents.