2-Hydroxymelatonin, a Predominant Hydroxylated Melatonin Metabolite in Plants, Shows Antitumor Activity against Human Colorectal Cancer Cells.
2-Hydroxymelatonin is a predominant hydroxylated melatonin metabolite in plants. To investigate whether it has potent cytotoxic effects on colorectal cancer cells, four colorectal cancer cell lines, Caco2, HCT116, DLD1, and CT26, were treated with 2-hydroxymelatonin and melatonin. 2-Hydroxymelatonin had a much lower IC50value than melatonin in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytotoxic effect of 2-hydroxymelatonin was much stronger than that of melatonin at high concentrations (1000 or 2000 μM) in HCT116, DLD1, and CT26 cells, but only at intermediate concentrations (250 or 500 μM) in Caco2 cells. The cytotoxicity of 2-hydroxymelatonin was induced through activation of the apoptotic signaling pathway, as confirmed by Hoechst staining and Annexin V-FITC/propidium iodide double labeling of cells treated with a lethal dose (1 mM). However, sub-lethal doses of 2-hydroxymelatonin inhibited the invasive ability of Caco2 cells. Epithelial-mesenchymal transition (EMT) markers were significantly regulated by 2-hydroxymelatonin. Overall, the anti-cancer activity of 2-hydroxymelatonin is more potent than that of melatonin. Taken together, 2-hydroxymelatonin exhibits potent anti-cancer activity against human colorectal cancer cells via induction of apoptosis and inhibition of EMT.
College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungangno, Sunchon, Jeonnam 57922, Korea. yangyi_520@hotmail.com.
Yi
Y
Yang
College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungangno, Sunchon, Jeonnam 57922, Korea. zhourui274@hotmail.com.
Rui
R
Zhou
College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungangno, Sunchon, Jeonnam 57922, Korea. sinbu17@naver.com.
So-Yeon
SY
Park
Department of Biotechnology, Bioenergy Research Center, College of Agriculture and Life Sciences, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Korea. kback@chonnam.ac.kr.
Kyoungwhan
K
Back
Department of Internal Medicine, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea. drwookyun@chonnam.ac.kr.
Woo Kyun
WK
Bae
Medical Research Center for Gene Regulation, Brain Korea 21 Project, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea. kimkk@chonnam.ac.kr.
Kyung Keun
KK
Kim
College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungangno, Sunchon, Jeonnam 57922, Korea. hangunkim@sunchon.ac.kr.
Hangun
H
Kim
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D008550:Melatonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; C487380:N-(2-(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)ethyl)acetamide; D008550:Melatonin
antitumor; colorectal cancer; hydroxymelatonin; melatonin; metabolite