Flavonoid morin inhibits proliferation and induces apoptosis of melanoma cells by regulating reactive oxygen species, Sp1 and Mcl-1.
Reactive oxygen species (ROS) is associated with cancer progression in different cancers, including melanoma. It also affects specificity protein (Sp1), a transcription factor. Flavonoid morin is known to inhibit growth of cancer cells, including lung cancer and breast cancer. Herein, we hypothesized that morin can inhibit cancer activities in melanoma by altering ROS generation. The aim of this study is to determine the effects of morin and its underlying mechanisms in melanoma cells. Effects of morin on cell proliferation and apoptosis were determined using standardized assays. Changes in pro-apoptotic and anti-apoptotic proteins were analyzed by western blot analysis. Cellular ROS levels and mitochondrial function were evaluated by measuring DCF-DA fluorescence and rhodamine-123 fluorescence intensities, respectively. Morin induced ROS production and apoptosis, as presented by increased proportion of cells with Annexin V-PE(+) staining and sub-G0/G1 peak in cell cycle analysis. It also downregulated Sp1, Mcl-1, Bcl-2, and caspase-3 but upregulated cleaved caspase-3, Bax, and PUMA. In immunohistochemical staining, Sp1 was overexpressed in melanoma tissues compared to normal skin tissues. Collectively, our data suggest that morin can induce apoptosis of melanoma cells by regulating pro-apoptotic and anti-apoptotic proteins through ROS, and may be a potential substance for treatment of melanoma.
['Lee|Yoon Jin|YJ|', 'Kim|Woo Il|WI|', 'Kim|Soo Young|SY|', 'Cho|Sung Woo|SW|', 'Nam|Hae Seon|HS|', 'Lee|Sang Han|SH|', 'Cho|Moon Kyun|MK|http://orcid.org/0000-0002-2180-9365']
D000972:Antineoplastic Agents, Phytogenic D017209:Apoptosis D045744:Cell Line, Tumor D049109:Cell Proliferation D015536:Down-Regulation D004354:Drug Screening Assays, Antitumor D005260:Female D005419:Flavonoids D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D008545:Melanoma D008928:Mitochondria D064549:Myeloid Cell Leukemia Sequence 1 Protein D017382:Reactive Oxygen Species D012878:Skin Neoplasms D016329:Sp1 Transcription Factor
Morin Proliferation Melanoma Sp1 Mcl-1 ROS