title: The chemomodulatory effects of resveratrol and didox on herceptin cytotoxicity in breast cancer cell lines.
abstract: Herceptin is considered an essential treatment option for double negative breast cancer. Resveratrol and didox are known chemopreventive agents with potential anticancer properties. The aim of the current study is to investigate the influence of resveratrol and didox on the cytotoxicity profile of herceptin in HER-2 receptor positive and HER-2 receptor negative breast cancer cell lines (T47D and MCF-7 cell lines, respectively). The IC50's of herceptin in T47D and MCF-7 were 0.133 ± 0.005 ng/ml and 23.3795 ± 1.99 ng/ml respectively. Equitoxic combination of herceptin with resveratrol or didox in T47D significantly reduced the IC50 to 0.052 ± 0.001 and 0.0365 ± 0.001 ng/ml, respectively and similar results were obtained in MCF-7. The gene expression of BCL-xl was markedly decreased in T47D cells following treatment with herceptin/resveratrol compared to herceptin alone. Immunocytochemical staining of HER-2 receptor in T47D cells showed a significant reduction after treatment with herceptin/resveratrol combination compared to herceptin alone. On the contrary, herceptin/didox combination had no significant effect on HER-2 receptor expression. Cell cycle analysis showed an arrest at G2/M phase for both cell lines following all treatments. In conclusion, herceptin/resveratrol and herceptin/didox combinations improved the cytotoxic profile of herceptin in both T47D and MCF-7 breast cancer cell lines.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Egypt.
authors.forename: Ghada A
authors.initials: GA
authors.lastname: Abdel-Latif
authors.affiliation: 1] Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Saudi Arabia [2] Department of Pharmacology, National Research Center, Giza, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Al-Abd
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Egypt.
authors.forename: Mariane G
authors.initials: MG
authors.lastname: Tadros
authors.affiliation: Department of Biochemistry, Faculty of science, King Abdulaziz University, Saudi Arabia.
authors.forename: Fahad A
authors.initials: FA
authors.lastname: Al-Abbasi
authors.affiliation: 1] Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Egypt [2] 57357 Children's Cancer Hospital, Cairo, Egypt.
authors.forename: Amany E
authors.initials: AE
authors.lastname: Khalifa
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Egypt.
authors.forename: Ashraf B
authors.initials: AB
authors.lastname: Abdel-Naim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D000068878:Trastuzumab / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3; D006877:Hydroxamic Acids; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077185:Resveratrol; D013267:Stilbenes; D000068878:Trastuzumab; C035419:3,4-dihydroxybenzohydroxamic acid