PMID- 26174122 OWN - NLM STAT- MEDLINE DCOM- 20161215 LR - 20161230 IS - 1600-0625 (Electronic) IS - 0906-6705 (Linking) VI - 24 IP - 12 DP - 2015 Dec TI - 7-Hydroxydehydronuciferine induces human melanoma death via triggering autophagy and apoptosis. PG - 930-5 LID - 10.1111/exd.12805 [doi] AB - 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. CI - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Wu, Pei-Fang AU - Wu PF AD - Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. FAU - Chiu, Chien-Chih AU - Chiu CC AD - Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. FAU - Chen, Chung-Yi AU - Chen CY AD - School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan, ROC. FAU - Wang, Hui-Min David AU - Wang HM AD - Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. AD - Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. AD - Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. AD - Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150821 PL - Denmark TA - Exp Dermatol JT - Experimental dermatology JID - 9301549 RN - 0 (7-hydroxydehydronuciferine) RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Aporphines) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Mitochondrial Proteins) RN - W26UEB90B7 (nuciferine) SB - IM MH - Animals MH - Antineoplastic Agents, Phytogenic/chemistry/*pharmacology MH - Apoptosis/drug effects MH - Aporphines/chemistry/*pharmacology MH - Autophagy/drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Drugs, Chinese Herbal/chemistry/pharmacology MH - Female MH - G2 Phase Cell Cycle Checkpoints/drug effects MH - Humans MH - Keratinocytes/cytology/drug effects MH - Medicine, Chinese Traditional MH - Melanoma/*drug therapy/metabolism/pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Microtubule-Associated Proteins/metabolism MH - Mitochondrial Proteins/metabolism MH - Nelumbo/chemistry MH - Plants, Medicinal/chemistry MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - 7-hydroxydehydronuciferine OT - apoptosis OT - autophagy OT - melanoma OT - metastasis EDAT- 2015/07/16 06:00 MHDA- 2016/12/16 06:00 CRDT- 2015/07/16 06:00 PHST- 2015/07/07 00:00 [accepted] PHST- 2015/07/16 06:00 [entrez] PHST- 2015/07/16 06:00 [pubmed] PHST- 2016/12/16 06:00 [medline] AID - 10.1111/exd.12805 [doi] PST - ppublish SO - Exp Dermatol. 2015 Dec;24(12):930-5. doi: 10.1111/exd.12805. Epub 2015 Aug 21.