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Published on: January 2, 2018
Oleanolic acid induces osteosarcoma cell apoptosis by inhibition of Notch signaling
1Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
Abstract:
Oleanolic acid (OA), a naturally occurring triterpenoid, exhibits potential antitumor activity in several tumor cell lines. Although the inhibition effects of OA on proliferation and survival in human cancers have been confirmed, the potential mechanism underlying OA-induced osteosarcoma cell death has not yet been fully elucidated. Our results in this study showed that OA inhibits proliferation and viability of osteosarcoma cells in a dose-dependent manner. Flow cytometry assays revealed that apoptosis in osteosarcoma cells was significantly induced by OA treatment, while this induction was blocked by Jagged1-mediated activation of Notch signaling. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. More importantly, our data revealed that OA treatment interrupted the balance between pro-apoptotic factors and anti-apoptotic factors in osteosarcoma cells by inhibition of the Notch signaling pathway. These data suggest that OA induces osteosarcoma cell apoptosis by targeting mitochondria in a Notch signaling-dependent manner. Thus, OA may be a promising drug for adjuvant chemotherapy in osteosarcoma.
Insights
Oleanolic acid (OA) effectively inhibits osteosarcoma cell growth and survival. It triggers programmed cell death (apoptosis) via the mitochondrial pathway, independent of Notch signaling, suggesting potential as an adjuvant cancer therapy.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Oleanolic acid (OA), a natural triterpenoid, shows promise as an anticancer agent.
- The precise mechanisms of OA's effects on osteosarcoma cell death require further investigation.
Purpose of the Study:
- To elucidate the mechanism of OA-induced apoptosis in osteosarcoma cells.
- To investigate the role of Notch signaling in OA's antitumor effects.
Main Methods:
- Dose-dependent proliferation and viability assays.
- Flow cytometry to detect apoptosis.
- Western blot and mitochondrial membrane potential assays.
- Investigation of Notch signaling pathway activation.
Main Results:
- OA significantly inhibited osteosarcoma cell proliferation and viability in a dose-dependent manner.
- OA treatment induced significant apoptosis, which was blocked by Jagged1-mediated Notch signaling.
- OA's mechanism involves the mitochondrial apoptosis pathway and disrupts the balance of apoptotic/anti-apoptotic factors.
- OA induces osteosarcoma cell apoptosis by targeting mitochondria in a Notch signaling-dependent manner.
Conclusions:
- Oleanolic acid induces osteosarcoma cell apoptosis through the mitochondrial pathway.
- The Notch signaling pathway plays a role in mediating OA's effects on osteosarcoma cells.
- OA demonstrates potential as an adjuvant therapeutic agent for osteosarcoma.
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