Betulinic acid and oleanolic acid modulate CD81 expression and induce apoptosis in triple-negative breast cancer cells through ROS generation

Lestari, Dian Yuliartha; Mastutik, Gondo; Mukono, Indri Safitri

doi:10.1007/s12032-024-02574-4

Med Oncol

2024

DOI: 10.1007/s12032-024-02574-4

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Betulinic acid and oleanolic acid modulate CD81 expression and induce apoptosis in triple-negative breast cancer cells through ROS generation

Dian Yuliartha Lestari,

Gondo Mastutik,

Indri Safitri Mukono

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2025

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Ziziphus mauritiana Leaf Extract Induces ROS-dependent Apoptosis by Downregulation of CD81 in MDA- MB 231 Triple Negative Breast Cancer Cells

Lestari,

Mastutik,

Mukono

2025

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Background. Breast cancer (BC) is the most prevalent cancer among women, with triple-negative breast cancer (TNBC) representing a particularly aggressive subtype. Current treatments often have limited efficacy and significant toxicity, highlighting the need for alternative therapeutic strategies. Ziziphus mauritiana (ZM) leaf extract contains triterpenoids which have been proven to be used as anticancer agents, but have not been studied in TNBC cells. Aim. To examine the triterpenoid content in ZM, especially BA and OA, ZM cytotoxicity, intracellular ROS levels, the amount of apoptosis, and CD81 expression on MDA-MB 231 cells after being given ZM. Material and Methods. The extract was prepared using a sequential extraction method. The presence of triterpenoids was confirmed via HPLC and LC-MS analysis. The cytotoxicity of the extract was assessed using the CCK-8 assay, while flow cytometry was employed to analyze CD81 expression and ROS levels. Apoptosis was quantified using an Annexin V-FITC/PI detection kit. Results. Based on HPLC, the BA content in ZM is 28.3 µg/ml, and the OA content is 13.4 µg/ml. ZM significantly reduced MDA-MB 231 cell viability by 28.28% at 400 µg/ml after 48 hours. Flow cytometry revealed a notable downregulation of CD81 expression (p < 0.0001) and an increase in intracellular ROS levels (p < 0.0001). Furthermore, ZM induced early and late apoptosis in treated cells, with increases of 2.34-fold and 2.66-fold, respectively. Conclusion. ZM leaf extract exhibits potent cytotoxic effects against MDA-MB 231 through ROS-dependent apoptosis and CD81 downregulation, suggesting its potential as a novel therapeutic agent for TNBC treatment.

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Ziziphus mauritiana Leaf Extract Induces ROS-dependent Apoptosis by Downregulation of CD81 in MDA- MB 231 Triple Negative Breast Cancer Cells

Lestari,

Mastutik,

Mukono

2025

Preprint

View full text Add to dashboard Cite

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Betulinic acid and oleanolic acid modulate CD81 expression and induce apoptosis in triple-negative breast cancer cells through ROS generation

Cited by 1 publication

References 36 publications

Ziziphus mauritiana Leaf Extract Induces ROS-dependent Apoptosis by Downregulation of CD81 in MDA- MB 231 Triple Negative Breast Cancer Cells

Ziziphus mauritiana Leaf Extract Induces ROS-dependent Apoptosis by Downregulation of CD81 in MDA- MB 231 Triple Negative Breast Cancer Cells

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