title: 3-O-[N-(p-fluorobenzenesulfonyl)-carbamoyl]-oleanolic acid, a semisynthetic analog of oleanolic acid, induces apoptosis in breast cancer cells.
abstract: Oleanolic acid (OA), a pentacyclic triterpene acid widely distributed in food and traditional herbal remedies, exhibits diverse therapeutic effects. OA has been subjected to various chemical modifications to optimize its anticancer effect. Among other analogs, 3-O-[N-(p-fluorobenzenesulfonyl)-carbamoyl]-oleanolic acid (PFOA) was semisynthesized from OA. This study evaluates the cytotoxic effects of PFOA on MDA-MB-231, MCF-7, BT-474, and T-47D human breast cancer cells. Acute treatment of PFOA inhibited breast cancer cell viability in a dose-dependent manner. Treatment of PFOA at cytotoxic doses significantly induced apoptosis in cancer cells as shown by flow cytometry analysis. Activation of apoptosis in MCF-7 and BT-474 cells seemed to be initiated through induction of Fas ligand, which resulted in activation of caspase-8 and PARP-1, whereas apoptosis in MDA-MB-231 cells was initiated by the activation of caspase-9, caspase-3 and PARP-1. The mechanism of apoptosis induction in T-47D involves activation of PARP-1. PFOA decreased the expression of EGFR, HER-2, MET and ERα in human breast cancer cell lines. These findings suggest that PFOA inhibits cell growth, activates apoptosis, and decreases the expression of key proteins involved in progression of breast cancer.
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Akl
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA; Department of Pharmacognosy, Faculty of Pharmacy, Helwan University, Helwan, Cairo 11795, Egypt.
authors.forename: Heba E
authors.initials: HE
authors.lastname: Elsayed
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Ebrahim
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Helwan University, Helwan, Cairo 11795, Egypt.
authors.forename: Eman G
authors.initials: EG
authors.lastname: Haggag
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Helwan University, Helwan, Cairo 11795, Egypt.
authors.forename: Amel M
authors.initials: AM
authors.lastname: Kamal
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA. Electronic address: elsayed@ulm.edu.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: El Sayed
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D020169:Caspases; D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D009828:Oleanolic Acid; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D013449:Sulfonamides; C000602451:3-O-(N-(p-fluorobenzenesulfonyl)carbamoyl)oleanolic acid; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C491743:MET protein, human
keywords: Apoptosis; Breast cancer; Caspase-8; Caspase-9; FAS ligand; Oleanolic acid