Hepatocellular carcinoma (HCC) is a serious concern worldwide. The published reports showed that aberrant CD95 receptor expression plays a critical role in apoptosis in liver cancer. While curcumin has shown promise in inducing apoptosis in liver cancer cells, its direct effects on CD95 expression during this process have not been thoroughly investigated. This study aims to quantitatively assess the expression of the CD95 receptor in HepG2 cells treated with different concentrations of curcumin using techniques such as fluorescence staining, single-molecule force spectroscopy (SMFS), and single-molecule recognition imaging (SMRI). Fluorescence staining results indicate a significant increase in CD95 expression following curcumin treatment. For the first time, SMFS and SMRI techniques were used to directly reveal the binding sites of CD95 on the cell membrane, with the number of binding sites increasing as the curcumin concentration increased. Additionally, the binding force between an antibody-modified probe and CD95 was strengthened with curcumin treatment, suggesting that curcumin enhances both the quantity and affinity of CD95 binding sites. This study provides new insights into curcumin-induced CD95-mediated apoptosis in liver cancer cells and highlights the potential of AFM techniques for investigating drug mechanisms. Overall, these findings may inform innovative therapeutic strategies for liver cancer and improve drug design processes.
Colorectal cancer (CRC) is the second most fatal cancer. Many studies have shown that cancer stemness contributes to resistance to conventional chemotherapy and poor prognosis. However, the mechanisms involved in maintaining cancer stemness in CRC are still obscure and few clinical drugs were used to target cancer stemness. Previous studies had reported CD95 increases the stemness of cancer cells with long-term stimulation of exogenous agonist CD95 ligand (CD95L). However, the expression of CD95L is relative low in many human tumor tissues. In this study, we found that CD95 was highly expressed in CRC cells, and in vitro it promoted the tumorsphere formation, chemotherapy resistance and in vivo tumor growth without stimulation of exogenous CD95L. Mechanistically, the bulk and single-cell RNA-sequencing results suggested that CD95 promotes stemness of CRC cells through upregulation of long non-coding RNAs metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1 ). MALAT1 knockdown inhibited CD95-induced tumorsphere formation and chemotherapy resistance. In summary, our findings reveal that CD95 has the capability to modulate cancer stemness via the action of the lncRNA MALAT1. Targeting CD95 may be a promising strategy to inhibit cancer stemness in CRC.
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