The histone methyltransferase SMYD2 is a novel therapeutic target for the induction of apoptosis in ovarian clear cell carcinoma cells
ONCOLOGY LETTERS
Authors: Kojima, Machiko; Sone, Kenbun; Oda, Katsutoshi; Hamamoto, Ryuji; Kaneko, Syuzo; Oki, Shinya; Kukita, Asako; Kawata, Akira; Honjoh, Harunori; Kawata, Yoshiko; Kashiyama, Tomoko; Sato, Masakazu; Taguchi, Ayumi; Miyamoto, Yuichiro; Tanikawa, Michihiro; Tsuruga, Tetsushi; Nagasaka, Kazunori; Wada-Hiraike, Osamu; Osuga, Yutaka; Fujii, Tomoyuki
Abstract
Previous studies have suggested that histone methylation can modulate carcinogenesis and cancer progression. For instance, the histone methyltransferase SET and MYND domain containing 2 (SMYD2) is overexpressed in several types of cancer tissue. The aim of the present study was to determine whether SMYD2 could serve a therapeutic role in ovarian clear cell carcinoma (OCCC). Reverse transcription-quantitative PCR was used to examine SMYD2 expression in 23 clinical OCCC specimens. Moreover, OCCC cell proliferation and cell cycle progression were also examined following small interfering RNA-mediated SMYD2 silencing or treatment with a selective SMYD2 inhibitor. SMYD2 was significantly upregulated in clinical OCCC specimens, compared with normal ovarian tissue. In addition, SMYD2 knockdown decreased cell viability as determined via a Cell Counting Kit-8 assay. Moreover, the proportion of cells in the sub-G(1) phase increased following SMYD2 knockdown, suggesting increased apoptosis. Treatment with the SMYD2 inhibitor LLY-507 suppressed OCCC cell viability. These results suggested that SMYD2 could promote OCCC viability, and that SMYD2 inhibition induced apoptosis in these cells. Thus, SMYD2 inhibitors may represent a promising molecular targeted approach for OCCC treatment.
Assessment of the Chemosensitivity of Uveal Melanoma Cells Ex Vivo
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE
Authors: Saakyan, S. V.; Tsygankov, A. Yu.; Moiseeva, N. I.; Karamysheva, A. F.; Garri, D. D.
Abstract
The study was designed to create a primary cell culture of uveal melanoma and to evaluate its resistance to chemotherapy. Of the obtained 20 samples of uveal melanoma, the primary cultures with proliferation sufficient for MTT test were derived in only 7 cases. However, even these cultures were unable to survive more than 4 passages; the cells accumulated melanin and underwent apoptosis. Retinol palmitate and nepafenac produced no cytotoxic effect on uveal melanoma cells. Of 5 cultures treated with sodium valproate (Convulex), no pronounced cytotoxic effect was observed in one culture (UM4); in 2 cultures, 50% cells died in the presence of the lowest drug concentration of 1.88 mg/ml; and in 2 cultures, the same effect was achieved at drug concentrations 7-10 mg/ml. The cytotoxic effect of treosulfan was evaluated in only 4 cultures of uveal melanoma: the drug exhibited pronounced antitumor activity on all cultures, in 2 cases, it was effective at a concentration of 0.16 mg/ml. Gemcitabine in a concentration of 2.5 mg/ml produced a pronounced cytotoxic effect in 4 out of 7 cultures (death of 70-80% cells) and induced death of similar to 45% cells in the remaining 3 cultures. Mitoxantrone had ambiguous effect: in 2 of 5 cultures, the drug in high concentrations stimulated the growth of tumor cells, but in 3 cultures, the drug even in minimum concentrations induced death of 70-80% cells.