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[Rhein lysinate induces apoptosis in breast cancer SK-Br-3 cells by inhibiting HER-2 signal pathway]
Ya-Jun Lin1, Yun-Hong Huang, Yong-Zhan Zhen
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Abstract:
This study is to investigate the effect of rhein lysinate on inducing human breast cancer cell line SK-Br-3 apoptosis and the role of HER-2 signal pathway in the apoptosis. MTT assay was used to detect SK-Br-3 cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The protein expression and the protein phosphorylation of HER-2 signal pathway were detected by Western blotting. The level of HER-2 mRNA was detected by RT-PCR and the level of HER-2 expression was also detected by immunofluorescence cytochemical methods. The results showed that rhein lysinate remarkably inhibited breast cancer SK-Br-3 cell proliferation. The IC50 value for 48 h treatment was 85 micromol x L(-1). Apoptosis in SK-Br-3 cells was induced by rhein lysinate in a dose dependent manner. The protein expressions of HER-2, NF-KB, and the protein phosphorylation of HER-2 were downregulated, however the protein expression of p53 and p21 was upregulated after rhein lysinate treatment. The level of HER-2 mRNA decreased by using RT-PCR assay and the level of HER-2 expression was also decreased by using immunofluorescence cytochemical assay after rhein lysinate treatment. It can be concluded that rhein lysinate could inhibit SK-Br-3 cell proliferation and induce apoptosis. HER-2/NF-kappaB/p53/p21 signal pathway might be involved in this process. Rhein lysinate has a good prospect to be an adjuvant chemotherapeutic drug.
Insights
Rhein lysinate effectively inhibits human breast cancer cell proliferation and induces apoptosis. This compound may target the HER-2/NF-kappaB/p53/p21 pathway, showing potential as an adjuvant chemotherapy drug.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Context:
- Human breast cancer cell line SK-Br-3 is a relevant model for studying cancer progression.
- The HER-2 signaling pathway plays a crucial role in the development and progression of certain breast cancers.
- Investigating novel therapeutic agents is essential for improving breast cancer treatment outcomes.
Purpose:
- To investigate the anti-cancer effects of rhein lysinate on SK-Br-3 cells.
- To elucidate the role of the HER-2 signaling pathway in rhein lysinate-induced apoptosis.
- To evaluate the potential of rhein lysinate as an adjuvant chemotherapeutic agent.
Summary:
- Rhein lysinate significantly inhibited SK-Br-3 cell proliferation with an IC50 of 85 µmol/L at 48 hours.
- The compound induced apoptosis in a dose-dependent manner, accompanied by downregulation of HER-2, NF-kappaB, and HER-2 phosphorylation.
- Upregulation of p53 and p21 protein expression was observed, along with decreased HER-2 mRNA and protein levels.
- The HER-2/NF-kappaB/p53/p21 signaling pathway is implicated in the observed anti-cancer effects.
Impact:
- Rhein lysinate demonstrates significant potential as a therapeutic agent for breast cancer.
- The findings suggest a novel mechanism of action involving the HER-2 signaling pathway.
- This study supports the development of rhein lysinate as an adjuvant therapy to enhance conventional chemotherapy.
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