Different susceptibility of colon cancer DLD-1 and LOVO cell lines to apoptosis induced by DMU-212, a synthetic resveratrol analogue.
The cytotoxic activity of DMU-212 has been shown to vary in cell lines derived from the same type of cancer, i.e. ovarian, breast and colorectal ones. However, the molecular mechanism of DMU-212 cytotoxicity has not been clarified in colon cancer cells. This study aims to elucidate the mechanism of antitumor effects of DMU-212 in two human colon cancer cell lines, DLD-1 and LOVO. We showed the stronger cytotoxic activity in DLD-1 cells in which DMU-212 evoked a greater pro-apoptotic effect as compared to that of LOVO cells. The analysis of the expression pattern of 84 apoptosis-related genes indicated transcripts specific to the mitochondria-mediated apoptosis pathway in both colon cancer cell lines used. We found that DMU-212 caused up-regulation of pro-apoptotic Bak1, Bok, Bik, Noxa, Bad, Bax, p53 and Apaf1 transcripts level in DLD-1 cell line, whereas anti-apoptotic Bcl-2, Bcl-xL and Bag1 mRNA expression was decreased. Changes in apoptosis-related genes expression were less pronounced in LOVO cells which did not express CYP1B1 protein and showed lower expression of CYP1A1 protein level than that in DLD-1 cells. Our results suggest that anticancer activity of DMU-212 is closely related to its biotransformation catalysed by these cytochrome P450 isoenzymes.
Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland. Electronic address: hanna.piotrowska@ump.edu.pl.
Hanna
H
Piotrowska
Krzysztof
K
Myszkowski
Ryszard
R
Amarowicz
Marek
M
Murias
Katarzyna
K
Kulcenty
Marcin
M
Wierzchowski
Jadwiga
J
Jodynis-Liebert
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
C482492:3,4,5,4'-tetramethoxystilbene; D000970:Antineoplastic Agents; D013267:Stilbenes; D001189:Aryl Hydrocarbon Hydroxylases; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D020169:Caspases; D000077185:Resveratrol
3,4,4′,5-Tetramethoxystilbene (DMU-212); Apoptosis; Cell cycle; Gene expression