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

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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 G2-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.

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Abbreviations

ACPH:

9-Phenyl acridine

Topo I:

Topoisomerase I

ΔΨ mt :

Mitochondrial membrane potential

PS:

Phophatidylserine

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labelling

Rh123:

Rhodamine 123

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Acknowledgments

Sudipta Bhowmik is supported with the University Research Scholarship from University of Kalyani (KU) and Dipanjan Guha is a recipient of UGC-RFMS scholarship, Govt. of India. The authors acknowledge instrumental facilities at the Dept. Biochemistry & Biophysics, KU funded by DST-FIST, Govt. of India.

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  1. Department of Biochemistry & Biophysics, University of Kalyani, Kalyani, 741235, West Bengal, India

    Rita Ghosh, Sudipta Bhowmik & Dipanjan Guha

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  1. Rita Ghosh
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Correspondence to Rita Ghosh.

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Ghosh, R., Bhowmik, S. & Guha, D. 9-Phenyl acridine exhibits antitumour activity by inducing apoptosis in A375 cells. Mol Cell Biochem 361, 55–66 (2012). https://doi.org/10.1007/s11010-011-1088-7

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  • DOI: https://doi.org/10.1007/s11010-011-1088-7

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