Abstract. – AIM: To investigate the effects of hypericin which is obtained from the plant Hy- pericum perforatum on the expression and the regulation of ADAMTS8 and ADAMTS9 genes in MCF7 breast cancer cells and on the viability of these cells. MATERIALS AND METHODS: MCF7 cells were cultured and were separately exposed to 2, 10 and 50 μl/mL of hypericin. After 24 hours, RNA was isolated from these cells and converted to cDNA. The expression levels of ADAMTS8 and ADAMTS9 genes were evaluated using the Reverse Tran- scription Polymerase Chain Reaction. XTT (2,3- bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H- tetrazolium-5-carboxanilide, disodium salt) cell vi- ability assay was used to determine cytotoxicity. RESULTS: ADAMTS9 expression in MCF7 cells were increased 1.8 and 3.6 fold with the use of 2 and 10 μl/mL of hypericin, respectively; and de- creased 0.7 fold with the use of 50 μl/mL of hy- pericin. There was no significant change in the ADAMTS8 expression. Rapid cell death was ob- served in the cancer cells when hypericin was used at a dose of ≥ 50 μl/mL. CONCLUSIONS: The increase in ADAMTS9 ex- pression can be a useful factor in the prevention of possible metastasis in breast cancer and for the occurrence of a tumor suppressive effect. Hy- pericin increases the expression of ADAMTS9, therefore, it may show its antitumoral and anti- apoptotic effects by means of ADAMTS9. Key Words: ADAMTS9, ADAMTS8, Hypericin, Breast cancer. Introduction The A Disintegrin-like And Metalloproteinase with ThromboSpondin motifs (ADAMTSs) are a European Review for Medical and Pharmacological Sciences Effect of hypericin on the ADAMTS-9 and ADAMTS-8 gene expression in MCF7 breast cancer cells Z. OCAK, M. ACAR 1 , E. GUNDUZ 1 , M. GUNDUZ 1 , K. DEMIRCAN 1 , U. UYETURK 2 , T. ÖZLÜ 3 Department of Medical Genetics, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey 1 Department of Medical Genetics, Faculty of Medicine, Fatih University, Ankara, Turkey 2 Department of Medical Oncology, Abant Izzet Baysal University Medical School, Bolu, Turkey 3 Department of Obstetrics and Gynecology, Abant Izzet Baysal University Medical School, Bolu, Turkey Corresponding Author: Zeynep Ocak, MD; e-mail: zeynep_ipek@yahoo.com 1185 family of secreted metalloproteinases with 19 members in humans 1 . ADAMTS proteinases are demonstrated to have roles in cell proliferation, apoptosis, tumor formation and hence in the di- rect interaction of cancer cells with extracellular matrix (ECM) 1,2 . Several ADAMTS members have been reported to function as anti-angiogenic and/or anti-tumorigenic molecules 1 . ADAMTS8 and 9 are the two anti-angiogenic members of the ADAMTS family with aggrecanase properties 2,3 . Both are among the target proteases for tumor suppression 2 . ADAMTS9 is located on the short arm of the 3 rd chromosome (3p) 4 . It is expressed in all embriogenic tissues. It was reported that ADAMTS9 gene can directly effect tumor pro- gression and metastasis by an anti-angiogenic ef- fect which occurs by means of fibroblast growth factor and vascular endothelial growth factor 5 . It was also shown to have a tumor suppressive role in esophageal and nasopharyngeal cancers, and a decreased expression of ADAMTS9 mRNA was observed in the metastatic tumors of these re- gions 6 . ADAMTS8 is located on the long arm of the 11 th chromosome (11q). It is expressed in the lungs and in the macrophage rich atherosclerotic plaques 3,7 . Low levels of ADAMTS8 in breast cancer have been reported to be associated with poor clinical outcome of these patients 8 . Breast cancer is the most common type of can- cer and the most common cause of cancer related deaths among women all over the world. Accord- ing to the joint report of World Health Organiza- tion and International Agency for Research on Cancer, breast cancer develops in 1,000,000 women/year and 370,000 die because of this dis- ease each year 9 . 2013; 17: 1185-1190