Flavonoid morin inhibits proliferation and induces apoptosis of melanoma cells by regulating reactive oxygen species, Sp
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Online ISSN 1976-3786 Print ISSN 0253-6269
RESEARCH ARTICLE
Flavonoid morin inhibits proliferation and induces apoptosis of melanoma cells by regulating reactive oxygen species, Sp1 and Mcl-1 Yoon Jin Lee1 • Woo Il Kim2 • Soo Young Kim2 • Sung Woo Cho1 Hae Seon Nam1 • Sang Han Lee1 • Moon Kyun Cho2
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Received: 13 November 2018 / Accepted: 22 April 2019 / Published online: 2 May 2019 The Pharmaceutical Society of Korea 2019
Abstract 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 antiapoptotic proteins through ROS, and may be a potential substance for treatment of melanoma.
& Moon Kyun Cho [email protected]; [email protected] 1
Molecular Cancer Research, Soonchunhyang University College of Medicine, Cheonan 31151, Republic of Korea
2
Department of Dermatology, Soonchunhyang University Hospital, Seoul 04401, Republic of Korea
Keywords Morin Melanoma Proliferation ROS Sp1 Mcl-1
Introduction Cancer is a major cause of death with a very high mortality rate in both developed and developing countries (Jemal et al. 2011). Among various types of cancers, cutaneous melanoma is one of the most common types of skin cancers with high rate of metastasis and mortality (Hofmann et al. 2000). Cutaneous melanoma arises from melanocytes thus it is deeply pigmented. It is usually primarily diagnosed by presentation of the skin lesion. Cutaneous melanoma progression is associated with oxidative stress and various cell signaling pathways (Hambright et al. 2015). Oxidative stress interferes with normal oxidation–reduction balance. It generates reactive oxygen species (ROS) that can damage cells and cause changes in the signaling process (Choi et al. 2014). ROS are byproducts of cellular metabolism and act as important signaling molecules. They are removed through
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