title: 9-phenyl acridine exhibits antitumour activity by inducing apoptosis in A375 cells.
abstract: Several acridine derivatives have been screened for their therapeutic potential and some are already established as antiprotozoan, antibacterial or anticancer agents. However, phenyl derivative at C-9 position of acridine had remained unexplored for their biological activity so far. In this report, we present our findings with 9-phenyl acridine (ACPH) as an anticancer agent. Both A375 and HeLa, two human cancer cell lines, were more sensitive to ACPH than normal cells namely human lymphocytes and also Chinese hamster V79 cells. ACPH also led to regression of tumour volume in mice. In A375 cells, we have shown that it caused DNA damage and blocked cell cycle progression at G(2)-M phase. Treatment with ACPH led to lowering of mitochondrial potential, upregulation of bax, release of cytochrome C and activation of caspase 3. As a new agent showing lower toxicity to normal cells and greater sensitivity towards cancerous cell line, ACPH shows promise as an effective cancer chemotherapeutic agent. ACPH treatment resulted in apoptotic death of cells through mitochondria-mediated caspase-dependent pathway.
authors.affiliation: Department of Biochemistry & Biophysics, University of Kalyani, Kalyani, West Bengal, India. ritadg2001@yahoo.co.in
authors.forename: Rita
authors.initials: R
authors.lastname: Ghosh
authors.forename: Sudipta
authors.initials: S
authors.lastname: Bhowmik
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Guha
mesh_terms: D000166:Acridines / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C571628:9-phenylacridine; D000166:Acridines; D000970:Antineoplastic Agents; C494826:BAX protein, human; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3