Surfactin induces ER stress-mediated apoptosis via IRE1-ASK1-JNK signaling in human osteosarcoma
Related Experiment Video
Updated: Oct 11, 2025
Fluorescence-based Measurement of Store-operated Calcium Entry in Live Cells: from Cultured Cancer Cell to Skeletal Muscle Fiber
Published on: February 13, 2012
Guo-Shou Wang1,2,3, Ji-Ying Chen1,2,3, Wei-Cheng Chen4,5
1Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Abstract:
Osteosarcoma, one of primary bone tumor in children and young adults, has poor prognosis and drug resistances to chemotherapy. In order to reinforce the conventional therapies and antagonize the osteosarcoma in patients, a novel strategy is required for developing a new treatment. In this study, surfactin, a natural product from Bacillus subtilis, showed the efficiency of cell death in osteosarcoma, but not in normal cells. Surfactin triggers ER stress mechanism by promoting the aberrant Ca2+ release from ER lumen and ER-signaling to mitochondrial dysfunction following caspases activation mediating cell apoptosis. Surfactin-induced ER stress not only upregulated of glucose-regulated protein 78/94 and IRE1-ASK1-JNK pathway but also leading to calpains and Bcl-2 proteins family involving the release of cytochrome c. The releases into cytosol trigger the cleavage of caspase-9 and caspase-3 to induce cell apoptosis. In this study, surfactin demonstrated the potential functions to trigger the ER stress, ER stress-associated IRE1-ASK1-JNK signaling pathway, mitochondrial dysfunction, and caspase activations leading to programmed cell apoptosis. Importantly, implicating the signaling pathway that regulates the connection between ER stress and mitochondrial dysfunction causing apoptosis associated with surfactin. These results indicated a potential application of surfactin strengthen current conventional therapies.
Insights
Surfactin, a natural compound, effectively induces cancer cell death in osteosarcoma by triggering endoplasmic reticulum stress and mitochondrial dysfunction. This natural product shows promise for enhancing current osteosarcoma treatments.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is a primary bone tumor in children and young adults with poor prognosis and chemotherapy resistance.
- Novel therapeutic strategies are needed to enhance conventional treatments for osteosarcoma.
Purpose of the Study:
- To investigate the potential of surfactin as a novel therapeutic agent against osteosarcoma.
- To elucidate the molecular mechanisms underlying surfactin-induced cell death in osteosarcoma cells.
Main Methods:
- Treatment of osteosarcoma and normal cells with surfactin.
- Analysis of endoplasmic reticulum (ER) stress markers, including Ca2+ release and protein upregulation (e.g., GRP78/94).
- Investigation of the ER-signaling to mitochondrial dysfunction pathway, including caspase activation and cytochrome c release.
Main Results:
- Surfactin selectively induced cell death in osteosarcoma cells but not in normal cells.
- Surfactin triggered ER stress by promoting aberrant Ca2+ release and upregulating ER stress markers.
- Surfactin activated the IRE1-ASK1-JNK pathway, leading to mitochondrial dysfunction, caspase activation, and apoptosis.
Conclusions:
- Surfactin demonstrates potential as an anti-osteosarcoma agent by inducing programmed cell death through ER stress and mitochondrial pathways.
- Surfactin's ability to trigger ER stress and mitochondrial dysfunction offers a novel therapeutic avenue.
- Surfactin may serve as a valuable adjunct to conventional therapies for osteosarcoma.
Related Concept Videos
01:31Regulation of the Unfolded Protein Response
01:22PI3K/mTOR/AKT Signaling Pathway
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
01:37The Unfolded Protein Response
01:17The Extrinsic Apoptotic Pathway
01:17Role of ER in the Secretory Pathway
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...