title: Breast cancer cells response to the antineoplastic agents cisplatin, carboplatin, and doxorubicin at the mRNA expression levels of distinct apoptosis-related genes, including the new member, BCL2L12.
abstract: Most apoptosis-related genes regulate cellular fate as a response to anticancer drugs. Modulations at the mRNA levels of such genes often correlate with the sensitivity of various types of cancer cells to chemotherapeutic reagents. The drugs cisplatin, carboplatin, and doxorubicin exhibit anticancer activity, the mechanism of which is not yet completely clarified, although they are known to modulate the expression of several genes including apoptosis-related genes, such as members of the BCL2 (Bcl-2) family. In order to define the significance of the expression patterns of such genes as a response to anticancer drug cytotoxic activity, we studied the possible alterations in the mRNA expression levels of various apoptosis-related genes, including the new member, BCL2L12, after cell treatment with distinct anticancer drugs (cisplatin, carboplatin, and doxorubicin), in the breast cancer cell line, MCF-7. The kinetics of cell toxicity was evaluated by the MTT method, whereas the expression levels of distinct apoptosis-related genes were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR), using gene-specific primers. The percentage of nonviable cells was upregulated with increasing concentrations and cell exposure time to the different anticancer drugs. Distinct modulations of apoptosis-related genes, at the mRNA level, were also observed. However, further work is required in order to ascertain whether the mRNA expression profile of such genes may provide evidence for their contribution to more specific and sensitive prediction of breast cancer response to treatment and therefore the rationale for individualized, more appropriate, and successful treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 15701 Athens, Greece.
authors.forename: Hellinida
authors.initials: H
authors.lastname: Thomadaki
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C430100:BCL2L12 protein, human; D009124:Muscle Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D004317:Doxorubicin; D016190:Carboplatin; D002945:Cisplatin