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Background <p>Sinomenine (SIN), the main active ingredient of <i>Sinomenium acutum</i> (Thunb.) Rehd. et Wils. Rhizomes, exhibits sensitive pharmacological activity against liver cancer. To elucidate the underlying mechanism, in vitro studies were conducted on human hepatocellular carcinoma (HCC) cell lines SMMC-7721 and HepG-2.</p> Methods and Results <p>SIN’s effects on cell viability, apoptosis, and expression of apoptosis-related genes and proteins were assessed. Immunofluorescence staining and Western blotting evaluated GRP78 cell-surface translocation and its role in apoptosis. SMMC-7721 cells were transfected with a GRP78 overexpression plasmid or treated with a GRP78 antibody to confirm the functional relevance of membrane GRP78 with SIN-induced apoptosis. Additionally, we examined the involvement of reactive oxygen species (ROS) in GRP78 translocation. In the results, SIN induced apoptosis in a dose- and time-dependent manner, and mainly through the endoplasmic reticulum (ER) apoptosis pathway. By increasing cellular ROS levels, the translocation of GRP78 from cytoplasm to cell membrane can be induced by SIN, and this translocation contributed to apoptosis.</p> Conclusions <p>SIN promoted the apoptosis of HCC cells by inducing GRP78 membrane translocation, mediated by increased ROS levels. This study provides new insight into SIN-induced GRP78 targeted antitumor therapy, which has important theoretical significance and application value.</p> Graphical abstract <p></p> <p>The aim of this study is to investigate the molecular mechanism of SIN against human liver cancer cells. In this study, SMMC-7721 and HepG-2 cells were used as the research objects, and GRP78, an important molecular chaperone of endoplasmic reticulum, was used as the research site to study the mechanism of SIN on the apoptosis of human liver cancer cells. The results showed that SIN could induce the increase of ROS level in tumor cells, and then change the distribution of GRP78 from cytoplasm to membrane, thereby promoting the apoptosis of tumor cells. It provides new ideas and research directions for the treatment of tumors with traditional Chinese medicine in the future.</p>

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Mechanism of sinomenine-induced apoptosis of human liver cancer cells via GRP78 membrane translocation

  • 期刊论文

  • 发表日期：

    2026年6月24日

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  • Miao Yu,
  • Yingjie Liu,
  • Ying Xu,
  • Wenlan Li,
  • Miao Yu

摘要

Background

Sinomenine (SIN), the main active ingredient of Sinomenium acutum (Thunb.) Rehd. et Wils. Rhizomes, exhibits sensitive pharmacological activity against liver cancer. To elucidate the underlying mechanism, in vitro studies were conducted on human hepatocellular carcinoma (HCC) cell lines SMMC-7721 and HepG-2.

Methods and Results

SIN’s effects on cell viability, apoptosis, and expression of apoptosis-related genes and proteins were assessed. Immunofluorescence staining and Western blotting evaluated GRP78 cell-surface translocation and its role in apoptosis. SMMC-7721 cells were transfected with a GRP78 overexpression plasmid or treated with a GRP78 antibody to confirm the functional relevance of membrane GRP78 with SIN-induced apoptosis. Additionally, we examined the involvement of reactive oxygen species (ROS) in GRP78 translocation. In the results, SIN induced apoptosis in a dose- and time-dependent manner, and mainly through the endoplasmic reticulum (ER) apoptosis pathway. By increasing cellular ROS levels, the translocation of GRP78 from cytoplasm to cell membrane can be induced by SIN, and this translocation contributed to apoptosis.

Conclusions

SIN promoted the apoptosis of HCC cells by inducing GRP78 membrane translocation, mediated by increased ROS levels. This study provides new insight into SIN-induced GRP78 targeted antitumor therapy, which has important theoretical significance and application value.

Graphical abstract

The aim of this study is to investigate the molecular mechanism of SIN against human liver cancer cells. In this study, SMMC-7721 and HepG-2 cells were used as the research objects, and GRP78, an important molecular chaperone of endoplasmic reticulum, was used as the research site to study the mechanism of SIN on the apoptosis of human liver cancer cells. The results showed that SIN could induce the increase of ROS level in tumor cells, and then change the distribution of GRP78 from cytoplasm to membrane, thereby promoting the apoptosis of tumor cells. It provides new ideas and research directions for the treatment of tumors with traditional Chinese medicine in the future.