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.

Direct detection of the anti‐cancer drug 9‐phenylacridine in tissues by graphite rod laser desorption vacuum‐ultraviolet post‐ionization mass spectrometry

“…Recent research has revealed two human cancer cell lines, A375 and Hela, which are more sensitive to ACPH than normal cells, namely human lymphocytes and Chinese hamster V79 cells. [41] In the present study, we verified the capability of graphiteassisted laser desorption single photon ionization mass spectrometry for the direct and fast analysis of the low molecular weight drug ACPH within complex biological tissues such as mice kidney. The potential of this technique for the quantification of small molecule drugs was also demonstrated by determining the detection sensitivity and acquiring a drug-time curve of ACPH in mice kidney.…”

“…In the present research, we used 9‐phenylacridine (ACPH) as the model drug molecule, as this compound, a DNA minor groove binder, has proven antitumour activity. Recent research has revealed two human cancer cell lines, A375 and Hela, which are more sensitive to ACPH than normal cells, namely human lymphocytes and Chinese hamster V79 cells …”

Acridine Yellow G Blocks Glioblastoma Growth via Dual Inhibition of Epidermal Growth Factor Receptor and Protein Kinase C Kinases

“…There are several possibilities to explain this phenomena: 1) in vitro, a 1 M dose is not high enough to trigger apoptosis, although it is potent enough to elicit cell cycle arrest and inhibits EGFR and PKCs; 2) in vivo, at doses of 50 or 100 mg/kg, the real drug exposure for C2 is more than 1 M in tumor samples, hence, the apoptosisinducing effect is evident in the tumors; 3) it is possible that C2 can be metabolized after oral administration, and changed into modified derivatives. For instance, some 9-position modified acridine elicited apoptosis in numerous human cancers (20,21).…”

New Aryl Derivatives of Acridine with Poly (ADP- Ribose) Polymerase 1 Inhibitory Activity: A Molecular Modeling Approach

“…Particularly important are the derivatives at C 9 position [16,17].The biological activities of phenyl-derivatives at C 9 position were so far less explored. From our earlier works the biological importance of some aryl derivatives of acridine are already documented [18,19] and the antitumor action have been demonstrated in different cancer cell lines as well as in animal model [20]. Aryl acridine derivatives can also potentiate cell killing by other agents (our unpublished results).…”