title: Anticancer effects of synthetic hexahydrobenzo [g]chromen-4-one derivatives on human breast cancer cell lines.
abstract: BACKGROUND
  Cancer results from a series of molecular changes that alter the normal function of cells. Breast cancer is the second leading cause of cancer death in women. To develop novel anticancer agents, new series of chromen derivatives were synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines.
  
  
  METHODS
  The growth inhibitory activities of synthesized hexahydrobenzo chromen-4-one were screened against six human cancer cell lines using an in vitro cell culture system (MTT assay). Fluorochrome staining (acridine orange/ethidium bromide double staining) and DNA fragmentation by the diphenylamine method were used to investigate the effects of most potent compounds on the process of apoptosis in breast cancer cell lines. To determine the mechanism of apoptosis, ROS and NOX production in treated breast cancer cells with compounds was evaluated.
  
  
  RESULTS
  The cytotoxicity data of tested compounds demonstrate these compounds had varying degree of toxicity. Compound 7h was the most potent compound with IC50= 1.8 ± 0.6 µg/mL against T-47D cell line. Analyses of the compounds treated (MCF-7, MDA-MB-231, and T-47D) cells by acridine orange/ethidium bromide double staining and DNA fragmentation by the diphenylamine method showed that the synthetic compounds induce apoptosis in the cells. A significant increase in ROS production was observed in T-47D cells treated with IC50value of compound 7g. Incubation with IC50value of synthetic compounds increased the NOX production in cell lines, especially T-47D cells.
  
  
  CONCLUSIONS
  Our results show that most compounds have a significant anti-proliferative activity against six human cancer cell lines. The observations confirm that chromen derivatives have induced the cell death through apoptosis.
authors.affiliation: Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Pordeli
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Nakhjiri
authors.affiliation: Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran, P. O. Box 3353-5111, Iran. safavi_maliheh@yahoo.com.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Safavi
authors.affiliation: Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Sussan Kabudanian
authors.initials: SK
authors.lastname: Ardestani
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000737:chemistry*; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D017382:Reactive Oxygen Species; D009569:Nitric Oxide
keywords: Anticancer; Apoptosis; Chromen