Evaluation of antineoplastic action of 5-aza-2'-deoxycytidine (Dacogen) and docetaxel (Taxotere) on human breast, lung and prostate carcinoma cell lines.
The antineoplastic activity of 5-aza-2'-deoxycytidine (5-AZA-CdR) and docetaxel (Taxotere, Taxo) alone or in combination against human MDA-MB-231 breast, Calu-6 lung and DU-145 prostate carcinoma cell lines was evaluated by clonogenic assay. We also investigated by RT-PCR the capacity of these agents to re-activate the expression of E-cadherin and maspin, two tumor suppressor genes that were silenced by DNA methylation. 5-AZA-CdR and Taxo in combination produced a greater loss of clonogenicity than either agent alone. In MDA-MB-231 breast carcinoma cells, Taxo did not interfere with the re-activation of E-cadherin and maspin genes by 5-AZA-CdR. These results provide a rationale for clinical trials on the combination of 5-AZA-CdR and Taxo in patients with advanced cancer.
Hurtubise
Annie
A
Département de pharmacologie, Université de Montréal, Hôpital Sainte-Justine, 3175 Côte Sainte-Catherine, Montréal, Québec H3T 1C5, Canada.
Momparler
Richard L
RL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000187:drug effects; D000077209:Decitabine; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology; D011506:Proteins / Q000235:genetics; D015843:Serpins / Q000096:biosynthesis / Q000235:genetics; D043823:Taxoids / Q000494:pharmacology*; D013997:Time Factors
D000970:Antineoplastic Agents; D015820:Cadherins; D011506:Proteins; C085344:SERPIN-B5; D015843:Serpins; D043823:Taxoids; D000077143:Docetaxel; D000077209:Decitabine; D004247:DNA; D001374:Azacitidine