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Betulinic acid and oleanolic acid modulate CD81 expression and induce apoptosis in triple-negative breast cancer
Dian Yuliartha Lestari1,2, Gondo Mastutik3, Indri Safitri Mukono4
1Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by a lack of hormones receptors and the HER2 receptor, making it unresponsive to targeted therapy. Triterpenoids such as betulinic acid (BA) and oleanolic acid (OA) have anticancer effects by inducing apoptosis in TNBC cells. CD81 is a tetraspanin that affects the growth and metastasis of cancer cells. To examine the effect of BA and OA on the viability of TNBC cell line (MDA-MB 231) by analyzing the CD81 expression, intracellular ROS, and apoptosis. The MDA-MB 231 cells was cultured and treated by BA and OA. The viability cell was evaluated by the CCK8 assay. This study analyzed the binding of BA and OA with CD81 using molecular docking and evaluated CD81 expression, intracellular ROS, and apoptosis by flow cytometry. The result showed that BA and OA inhibited viability of MDA-MB-231 cells. BA and OA bind to CD81 in silico, with binding affinities of 9.0 kcal/mol for BA and 7.2 kcal/mol for OA. Flow cytometry results revealed that BA can downregulate CD81 expression. BA and OA also increased intracellular ROS levels and induced apoptosis. These findings suggest that BA and OA, especially BA, can modulate CD81 expression and promote apoptosis in TNBC cells through the generation of ROS, thereby offering a potential therapeutic strategy for the treatment of TNBC.
Insights
Betulinic acid (BA) and oleanolic acid (OA) show promise for treating triple-negative breast cancer (TNBC). These compounds inhibit cancer cell viability by increasing ROS and apoptosis, with BA also downregulating CD81 expression.
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) lacks hormone and HER2 receptors, limiting treatment options.
- Triterpenoids like betulinic acid (BA) and oleanolic acid (OA) exhibit anticancer properties.
- CD81, a tetraspanin, influences cancer cell growth and metastasis.
Purpose of the Study:
- To investigate the effects of BA and OA on MDA-MB-231 TNBC cell viability.
- To analyze the impact of BA and OA on CD81 expression, intracellular ROS, and apoptosis.
- To explore the potential therapeutic role of BA and OA in TNBC treatment.
Main Methods:
- Cell culture and treatment of MDA-MB-231 cells with BA and OA.
- Cell viability assessment using the CCK8 assay.
- Molecular docking to analyze BA and OA binding to CD81.
- Flow cytometry to evaluate CD81 expression, intracellular ROS, and apoptosis.
Main Results:
- BA and OA significantly inhibited the viability of MDA-MB-231 cells.
- Molecular docking revealed binding affinities of -9.0 kcal/mol for BA-CD81 and -7.2 kcal/mol for OA-CD81.
- BA treatment downregulated CD81 expression.
- Both BA and OA increased intracellular ROS levels and induced apoptosis in TNBC cells.
Conclusions:
- BA and OA demonstrate efficacy in reducing TNBC cell viability.
- These triterpenoids promote apoptosis and increase ROS generation in cancer cells.
- BA's ability to modulate CD81 expression suggests a specific mechanism in TNBC treatment, offering a potential therapeutic strategy.
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