Abstract

Sinomenine (SIN) is a natural isoquinoline alkaloid extracted from the Chinese medicinal plant Sinomenium acutum with promising antitumor properties. Although its antitumor effect and mechanism have been studied, its effects on the structure and function of tumor cell membranes remain unclear. This study aimed to evaluate the antitumor effect of SIN on H22 hepatoma-bearing mice and its mechanism of action on tumor cell membranes, and the tumor inhibition rate and life extension rate were examined. Flow cytometry was used to evaluate the dose-dependent induction of apoptosis in H22 cells. The main components of tumor cell membrane, including total protein, cholesterol and sialic acid (SA) were characterized. The ultrastructure of cell membrane was observed using transmission electron microscopy (TEM). Furthermore, SIN’s effect on the function of cell membranes was studied by analyzing fluidity, sealing, and ion pump activity. The results demonstrated that SIN effectively inhibited the growth of liver cancer cells in vivo and prolonged the lifespan of H22 hepatoma-bearing mice. SIN induced apoptosis of H22 cells in a dose-dependent manner, significantly reduced total protein, cholesterol, and SA contents in H22 cell membranes, and significantly decreased the fluidity, sealing, Na+/K+-ATPase and Ca2+/Mg2+-ATPase activities of H22 cell membranes with increasing doses. Overall, these findings suggested that SIN reduced the main component contents of H22 cell membranes, leading to changes in structure and function of cell membrane, ultimately resulting in tumor cell apoptosis and inhibition of tumor growth. The findings indicated that SIN has great potential as a biomaterial for anti-liver cancer drugs, and provides new ideas and methods for developing antitumor drugs through membrane pharmacology.

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