title: Lipotropes enhance the anti-proliferative effect of chemotherapeutic drugs in MCF-7 human breast cancer cells.
abstract: Increasing evidence indicates that dietary intake of methyl nutrients is associated with the risk of breast cancer. Lipotropes are methyl group-containing essential nutrients (methionine, choline, folate and vitamin B12) which play key roles in one-carbon metabolism; however, little is known about the implications of lipotropes in possible tumor-suppressive effects with chemotherapeutic drugs for breast cancer. In the present study, we investigated the in vitro effects of lipotropes on cell growth and apoptosis of MCF-7 human breast cancer cells. Cells were cultured and treated with lipotropes, and cell proliferation, apoptosis and gene expression were determined. Also, the possible synergistic effects of lipotropes with anticancer drugs, the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and doxorubicin (DOX), were examined. Lipotropes significantly reduced the growth of MCF-7 cells and increased apoptosis as well as upregulation of caspase-3 and tumor protein 53 (p53) enzyme activities. Gene transcription, as measured by quantitative real-time PCR, revealed a significant increase of p53 mRNA in MCF-7 cells treated with lipotropes, but there were no differences in two drug-resistant related genes. Moreover, lipotropes showed significant additive effects with SAHA and DOX on cell growth inhibition. These results suggest that lipotropes induce apoptosis, inhibit cell growth, and display anti-proliferative effects with SAHA and DOX in MCF-7 cells. Owing to the tumor-suppressive effects observed, lipotropes in combination with chemotherapeutic drugs may be tested further in animal models as potential therapeutic agents for reducing breast cancer risk.
authors.affiliation: Department of Animal Sciences, North Dakota State University, Fargo, ND 58102, USA.
authors.forename: Kyongshin
authors.initials: K
authors.lastname: Cho
authors.forename: Lawrence
authors.initials: L
authors.lastname: Mabasa
authors.forename: Mark W
authors.initials: MW
authors.lastname: Walters
authors.forename: Chung S
authors.initials: CS
authors.lastname: Park
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms; D049109:Cell Proliferation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008082:Lipotropic Agents / Q000494:pharmacology*; D061986:MCF-7 Cells; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D000077337:Vorinostat
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D004317:Doxorubicin; D047628:Estrogen Receptor alpha; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008082:Lipotropic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53; D000077337:Vorinostat; C116614:ABCG2 protein, human; C506487:ESR1 protein, human; C495901:TP53 protein, human; C497206:MDM2 protein, human; C421109:multidrug resistance-associated protein 1