Targeting the AKT/mTOR axis: pectolinarigenin induces autophagy and apoptosis in human cervical cancer cells

TL;DR

This study shows that pectolinarigenin, a plant compound, can fight cervical cancer by triggering cell death and autophagy through the AKT/mTOR pathway.

Contribution

This is the first study to demonstrate that pectolinarigenin induces autophagy and apoptosis in cervical cancer via AKT/mTOR inhibition.

Findings

Pectolinarigenin reduced Bcl-2 and increased pro-apoptotic markers Bax and cleaved caspase-3 in cervical cancer cells.

Pectolinarigenin elevated LC3B II levels, indicating autophagy induction, which was inhibited by 3-MA.

Pectolinarigenin suppressed the AKT/mTOR signaling pathway, a key regulator of autophagy and apoptosis in cancer cells.

Abstract

Cervical cancer (CC) remains a significant global health issue, accounting for approximately 7% of all cancer cases in women. This study investigated the anti-cancer potential of pectolinarigenin (PEC), a bioactive compound derived from plants, aiming to explore its therapeutic effects and underlying mechanisms against CC. By integrating network pharmacology analysis with cellular assays, we identified 13 key targets of PEC related to CC, with molecular docking highlighting AKT as a primary target. Experimentally, PEC demonstrated strong anti-cancer effects on cervical cancer both in vivo and in vitro. Western blotting analysis revealed that PEC treatment led to a dose-dependent decrease in Bcl-2 protein levels, coupled with increased activation of pro-apoptotic markers Bax and cleaved caspase-3 in both cell lines. PEC also elevated the levels of LC3B II protein, indicating the induction of autophagy. Notably, this autophagic response was inhibited by 3-MA, an autophagy inhibitor, suggesting that PEC played a regulatory role in activating autophagy. Mechanistic studies confirmed that PEC effectively suppressed the AKT/mTOR signaling pathway, a critical regulator of both autophagy and apoptosis in cancer cells. Overall, this is the first study to demonstrate that PEC exerted potent anti-cancer effects against CC by concurrently inducing autophagy and apoptosis through targeted inhibition of the AKT/mTOR pathway. These findings highlighted the potential of PEC as a promising natural therapeutic agent for CC, paving the way for new treatment strategies. Further comprehensive research is warranted to fully explore PEC’s therapeutic capabilities and to develop innovative anti-cancer therapies.

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