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Published on: August 17, 2018
Physalin B from Physalis angulata triggers the NOXA-related apoptosis pathway of human melanoma A375 cells
Chia-Chun Hsu1, Yang-Chang Wu, Lynn Farh
1Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, and Department of Internal Medicine, E-DA Hospital, Kaohsiung 807, Taiwan.
Abstract:
Melanoma is a lethal form of skin cancer that can metastasize rapidly. While surgery and radiation therapy provide palliative therapy for local tumor growth, systemic therapy is the mainstay of treatment for metastatic melanoma. However, limited chemotherapeutic agents are available for melanoma treatment. In this study, we investigated the anti-melanoma effect of physalin B, the major active compound from a widely used herb medicine, Physalis angulata L. This study demonstrated that physalin B exhibits cytotoxicity towards v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutated melanoma A375 and A2058 cells (the IC50 values are lower than 4.6 μg/ml). Cytotoxicity is likely resulted from apoptosis since the apoptotic marker phosphatidylserine are detected immediately under physalin B treatment and apoptotic cells formation. Further examination revealed that physalin B induces expression of the proapoptotic protein NOXA within 2 h and later triggers the expression of Bax and caspase-3 in A375 cells. These results indicate that physalin B can induce apoptosis of melanoma cancer cells via the NOXA, caspase-3, and mitochondria-mediated pathways, but not of human skin fibroblast cells and myoblastic cells. Thus, physalin B has the potential to be developed as an effective chemotherapeutic lead compound for the treatment of malignant melanoma.
Insights
Physalin B, derived from Physalis angulata L., shows potent anti-melanoma effects by inducing cancer cell apoptosis. This natural compound offers a promising new avenue for treating metastatic melanoma.
Area of Science:
- Natural Products Chemistry
- Cancer Biology
- Pharmacology
Background:
- Melanoma is an aggressive skin cancer with limited systemic treatment options.
- Metastatic melanoma requires effective chemotherapeutic agents for treatment.
- Physalis angulata L. is a medicinal herb with potential therapeutic compounds.
Purpose of the Study:
- To investigate the anti-melanoma effects of physalin B, a compound from Physalis angulata L.
- To determine the mechanism of action of physalin B on melanoma cells.
- To evaluate physalin B as a potential chemotherapeutic lead for melanoma.
Main Methods:
- Cytotoxicity assays on BRAF-mutated melanoma cell lines (A375, A2058).
- Apoptosis detection using phosphatidylserine externalization and apoptotic cell morphology.
- Western blot analysis to assess proapoptotic protein (NOXA, Bax, caspase-3) expression.
Main Results:
- Physalin B exhibited significant cytotoxicity against BRAF-mutated melanoma cells (IC50 < 4.6 μg/ml).
- Cytotoxicity was mediated by apoptosis, evidenced by phosphatidylserine detection and cell morphology changes.
- Physalin B induced NOXA, Bax, and caspase-3 expression, indicating a mitochondria-mediated apoptotic pathway.
Conclusions:
- Physalin B effectively induces apoptosis in melanoma cells through NOXA, caspase-3, and mitochondria-dependent pathways.
- Physalin B demonstrated selectivity, sparing normal human skin fibroblast and myoblastic cells.
- Physalin B shows potential as a novel chemotherapeutic lead compound for malignant melanoma treatment.
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