Pharmacological, Mechanistic, and Pharmacokinetic Assessment of Novel Melatonin-Tamoxifen Drug Conjugates as Breast Cancer Drugs

• Published in: Molecular pharmacology Vol. 96; no. 2; pp. 272 - 296
• Main Authors: Hasan, Mahmud, Marzouk, Mohamed Akmal, Adhikari, Saugat, Wright, Thomas D., Miller, Benton P., Matossian, Margarite D., Elliott, Steven, Wright, Maryl, Alzoubi, Madlin, Collins-Burow, Bridgette M., Burow, Matthew E., Holzgrabe, Ulrike, Zlotos, Darius P., Stratford, Robert E., Witt-Enderby, Paula A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2019; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Biological Availability; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Drug Resistance, Neoplasm - drug effects; Estrogen Receptor alpha - metabolism; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; MAP Kinase Signaling System - drug effects; MCF-7 Cells; Melatonin - administration & dosage; Melatonin - pharmacokinetics; Melatonin - pharmacology; Mice; Receptor, Melatonin, MT1 - metabolism; Tamoxifen - administration & dosage; Tamoxifen - pharmacokinetics; Tamoxifen - pharmacology; BC; PR; MT1R; MTT; C2; LLQ; C4; DMEM; NF-κB; C5; QC; PI3K; C9; FBS; TNBC; WT; HPLC; MMC; PDX; C15; MS; GPR30; ER; ESR1; TAM-d5; MEK; TamR; LC; HER2

Tamoxifen is used to prevent and treat estrogen receptor–positive (ER+) breast cancer (BC); however, its chronic use can increase uterine cancer risk and induce tamoxifen resistance. Novel melatonin-tamoxifen drug conjugates may be promising to treat BC and may help offset the adverse effects of tam...