title: 7-Hydroxydehydronuciferine induces human melanoma death via triggering autophagy and apoptosis.
abstract: Melanoma is the deadliest cancer. We identified 7-hydroxydehydronuciferine (7-HDNF) isolated from the leaves of Nelumbo nucifera Gaertn cv. Rosa-plena to be a bio-active agent that antagonizes melanoma tumor growth in mice xenograft model in vivo. Cell proliferation assay demonstrated strong anticancer effects of 7-HDNF to exhibit a dose-dependent behaviour and displayed minor cytotoxicities on normal human skin cells, including epidermal keratinocytes and melanocytes, and dermal fibroblasts. With acridine orange (AO) staining and flow analysis, we found 7-HDNF induced the formation of intracellular vacuoles and the augmentation of acidic vesicular organelles (AVO). The apoptotic cell death ratio was measured via two-dimensional flow cytometry by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double stained to confirm the cellular membrane asymmetry lost. One-dimensional flow cytometric analysis showed 7-HDNF increased the cellular arrest in cell cycle at the G2/M phase. Through Western blot examinations, protein expressions were discovered to verify autophagy and apoptosis response mechanisms sharing the associated pathways. Finally, 7-HDNF presented a high-quality antimigratory activity in wound-healing assay. Overall, 7-HDNF presented high-quality anticancer bio-functions and inhibited melanoma tumor growth in vivo and in vitro.
authors.affiliation: Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Wu
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chiu
authors.affiliation: School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan, ROC.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.|Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.|Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC.
authors.forename: Hui-Min David
authors.initials: HM
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001060:Aporphines / Q000737:chemistry / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008516:Medicine, Chinese Traditional; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D031653:Nelumbo / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: C000611464:7-hydroxydehydronuciferine; D000972:Antineoplastic Agents, Phytogenic; D001060:Aporphines; D004365:Drugs, Chinese Herbal; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C008692:nuciferine
keywords: 7-hydroxydehydronuciferine; apoptosis; autophagy; melanoma; metastasis