Evaluating the antitumor activity of combined photochemotherapy mediated by a meso-substituted tetracationic porphyrin and adriamycin.

ABSTRACT

The combined anticancer modality comprising porphyrins as photodynamic sensitizers and anticancer drugs has been an interesting subject for many researchers. In this study, the photochemotherapeutic effect mediated by simultaneous photoactivation of tetracationic meso-tetrakis(N-methyl-4-pyridyl) porphine tetratosylate (TMPyP) and adriamycin (ADM) were explored using human hepatocellular carcinoma cell line (HePG2). The efficiency of TMPyP acting in concert with ADM in the dark and in the presence of photoirradiation was evaluated, by studying cell viability, caspase-3 activity and ultrastructural changes in the cells after incubation with each of the two agents, separately, or simultaneously as a co-mixture. Under dark conditions, the simultaneous incubation of cells with TMPyP and ADM significantly enhanced cell death by 1.8 folds and 1.3 folds, compared with TMPyP or ADM treatment, respectively. After photoirradiation, the antiproliferative effect of the co-treatment with TMPyP and ADM increased further by 2 folds. Transmission electron microscopy and the measurements of caspase-3 levels in treated cells revealed that the co-treatment of cells with ADM and TMPyP followed by light irradiation directed the cell death towards necrosis and abrogated the apoptotic cell death pathway, which was exhibited in cells treated with ADM in absence and in presence of photoirradiation.