Abstract |
Two new organoselenium compounds, 4-ethyl-4-hydroxy-2-p-tolyl-4H-5,6-dihydro-1,3-selenazine (TS-2) and 4-hydroxy-4-methyl-6-propyl-2-p-tolyl-4H-5,6-dihydro-1,3-selenazine++ + (TS-6) were investigated for their inhibitory effect on the growth of 8 human tumor cell lines, including stomach, lung, prostate and colon cancer cell lines, in vitro. Both TS-2 and TS-6 exhibited the strongest cytotoxicity against a gastric adenocarcinoma (TMK-1) among 8 human tumor cell lines, and their IC50 were 2.38 microM and 2.78 microM, respectively. Twenty-four-h exposure of TMK-1 cells to TS-2 or TS-6 (0.1-100 microM) in the absence of serum led to a concentration-dependent increase of cytotoxicity. Exposure of TMK-1 cells to TS-2 or TS-6 (5, 10 or 20 microM) in the presence of 5% serum resulted in significant inhibition of TMK-1 cell proliferation in a concentration- and time-dependent manner. Morphological changes including shrinkage of the nucleus, and DNA ladder fragmentation, which are considered to be the typical features of apoptosis, were observed in TMK-1 cells in response to TS-2 or TS-6. Furthermore, the caspase-3 activity in TMK-1 cells treated with TS-2 or TS-6 was also found to be increased in a time-dependent manner, in parallel with the induction of DNA fragmentation. Taken together, the results of the present study suggest that the inhibition of growth of TMK-1 cells by TS-2 and TS-6 is mediated by the induction of apoptosis.
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Authors | W Wu, K Murakami, M Koketsu, Y Yamada, I Saiki |
Journal | Anticancer research
(Anticancer Res)
1999 Nov-Dec
Vol. 19
Issue 6B
Pg. 5375-81
ISSN: 0250-7005 [Print] Greece |
PMID | 10697564
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 4-ethyl-4-hydroxy-2-(4-tolyl)-4H-5,6-dihydro-1,3-selenazine
- 4-hydroxy-4-methyl-6-propyl-2-(4-tolyl)-4H-5,6-dihydro-1,3-selenazine
- Antineoplastic Agents
- Organoselenium Compounds
- CASP3 protein, human
- Caspase 3
- Caspases
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Topics |
- Adenocarcinoma
(enzymology, pathology)
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Caspase 3
- Caspases
(metabolism)
- Cell Division
(drug effects)
- Humans
- Organoselenium Compounds
(pharmacology)
- Stomach Neoplasms
(enzymology, pathology)
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