9-Phenyl acridine exhibits antitumour activity by inducing apoptosis in A375 cells

• Published in: Molecular and cellular biochemistry Vol. 361; no. 1-2; pp. 55 - 66
• Main Authors: Ghosh, Rita, Bhowmik, Sudipta, Guha, Dipanjan
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.02.2012; Springer; Springer Nature B.V
• Subjects: Acridines - pharmacology; Acridines - therapeutic use; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Biochemistry; Biomedical and Life Sciences; Cancer; Cardiology; Caspase 3 - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cellular biology; Chemotherapy; Cricetinae; Cricetulus; Cytochrome c; Cytochromes c - metabolism; DNA Damage; Drug Screening Assays, Antitumor; Enzymes; G2 Phase Cell Cycle Checkpoints - drug effects; Gene Expression; Health aspects; Humans; Life Sciences; Lymphocytes; Medical Biochemistry; Membrane Potential, Mitochondrial - drug effects; Mice; Mitochondria; Mitochondrial DNA; Oncology; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Tumor Burden - drug effects; Tumors; Cytochrome; Bax; Caspase 3; Antitumour activity; 9-Phenyl acridine; Mitochondrial membrane potential
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-011-1088-7

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.