Polysaccharides from Sepia Esculenta Ink Promote Apoptosis via Inhibition of Autophagy in Cisplatin-exposed Triple-Negative Breast Cancer Cells.

Introduction: Sepia Ink Polysaccharide (SIP) is a well-characterized, marinederived glycosaminoglycan with demonstrated multifunctional properties; however, its pharmacological mechanisms remain unclear. This study aims to investigate the anti-tumor mechanism of SIP1 from Sepia esculenta ink in the treatment of triple-negative breast cancer (TNBC), with a focus on apoptosis and autophagy.

Methods: MDA-MB-231 cells exposed to cisplatin (CP) and SIP1 were assessed for apoptosis and autophagy by evaluating cell morphology, apoptosis and autophagy rates, and the expression of key genes involved in these processes using double staining, flow cytometry, and Western blotting.

Results: The data revealed that SIP1 induced apoptosis in TNBC cells, as demonstrated by an increased apoptosis rate, an elevated expression level of the Caspase-3 protein, a decreased expression of Bcl-2, and an elevated Bax/Bcl-2 ratio. Additionally, SIP1 did not impact autophagy. CP induced both apoptosis and autophagy of breast cancer cells. The combination of SIP1 and CP exhibited synergistic effects, enhancing apoptosis by 2.33-fold compared to SIP1 alone and 1.25-fold compared to CP alone, while simultaneously reducing autophagy levels (0.84-fold compared to CP alone), as verified by the Beclin 1 protein content.

Discussion: This work discovered that SIP1, a sulfated glycosaminoglycan with a low content of sulfate ester groups derived from Sepia esculenta ink, induced apoptosis by inhibiting autophagy, providing a novel perspective for a deeper understanding of the anti-- tumor mechanism of SIP. Currently, the underlying molecular mechanisms by which SIP1 modulates the crosstalk between apoptosis and autophagy in TNBC cells remain unknown and require further investigation.

Conclusion: This study demonstrates that SIP1 is effective in inducing apoptosis and promotes cisplatin-induced apoptosis by repressing cisplatin-induced autophagy in MDA-MB-231 cells.