title: Physalin B from Physalis angulata triggers the NOXA-related apoptosis pathway of human melanoma A375 cells.
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.
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, and Department of Internal Medicine, E-DA Hospital, Kaohsiung 807, Taiwan.
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Hsu
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Lynn
authors.initials: L
authors.lastname: Farh
authors.forename: Ying-Chi
authors.initials: YC
authors.lastname: Du
authors.forename: Wei-Kung
authors.initials: WK
authors.lastname: Tseng
authors.forename: Chau-Chung
authors.initials: CC
authors.lastname: Wu
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D032321:Physalis / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D012632:Secosteroids / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012632:Secosteroids; D051028:bcl-2-Associated X Protein; C033270:physalin B; D053148:Caspase 3; D004264:DNA Topoisomerases, Type I