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Acridines are an important class of bioactive molecules having varied uses. Its derivative, 9-phenylacridine (ACPH) had been found to exhibit antitumor activity both in cell lines and in vivo model. Its DNA binding ability and absorbance in the ultraviolet range encouraged us to investigate its role as a photosensitizer with UVA radiation. We investigated the effects of ACPH prior to UVA exposure on in vitro DNA through photo-cleavage assay. Effect of such treatment was also studied in cultured A375 melanoma cells. Endpoints studied included morphological changes, evaluation of cellular viability, scratch assay, intracellular reactive oxygen species (ROS) production, DNA damage, lipid peroxidation, glutathione (GSH) level, autophagy, cell cycle progression, depletion of mitochondrial membrane potential (ΔΨmt), induction of apoptosis and Hoechst dye efflux assay. Our findings indicated that ACPH could sensitize damage to DNA induced by UVA both in vitro and in cells. It could also potentiate cell killing by UVA. It arrested cells in G 2 /M phase and induced apoptotic death through mitochondria mediated pathway. This sensitization was through enhancement of intracellular ROS. Our findings also indicated that the stem cells side population was reduced on such treatment. The findings are important as it indicates ACPH as a promising photosensitizer and indicates its possible role in photodynamic therapy.

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Background: Exposure to sunlight, mainly UVA, leads to typical changes in the features of the skin known as photoaging. UVA irradiation induces the expression of proteases that are responsible for the degradation of the extracellular matrix proteins to results in photoaging; it also downregulates the expression of proteins that are needed for the skin structure. Since, it is known that cells in the neighborhood of irradiated cells, but not directly exposed to it, often manifest responses like their irradiated counterparts, it is important to evaluate if these bystander cells too, can contribute to photoaging.Methods and Results: UVA induced cell cycle arrest have been associated with photoaging, from ow cytometry analysis we found that there was an induction of cell cycle arrest at the G 1 /S phase in the UVAbystander cells. The expression of some key photoaging marker genes likes, matrix metalloproteinases (MMP-1, MMP-3, MMP-9), cyclooxygenase-2 (COX-2), collagen1 and elastin were assessed from qRT-PCR.Upregulation of MMP-1 and COX-2, downregulation of collagen1 and elastin, along with suppression below normal expression for MMP-3 and MMP-9 was observed in the UVA-bystander A375 cells. Conclusion: Our ndings for the rst time suggest the contribution of UVA-bystander cells to the process of photoaging. HighlightsG 1 /S cell cycle arrest was observed in UVA-bystander A375 cells.The expression of MMP-1 & COX-2 was upregulated in UVA-bystander A375 cells.Collagen 1 & elastin expression was also downregulated in these bystander cells.Expression of MMP-3 & -9 in the UVA-bystander cells lower than that in control cells.

Poly (C) binding proteins (PCBPs) are members of sequence specific RNA binding protein family with conserved KH domain. There are four identified isoforms such as Pcbp1 or α-CP1 (α-Complex proteins), Pcbp2 or α-CP2, Pcbp3 or α-CP3 and Pcbp4 or α-CP4. Among them Pcbp1 and Pcbp2 are the most studied and found to be associated with various cellular functions such as transcriptional regulations, translational regulations and mRNA stability. Although two proteins share extensive similarity, they differ in function and localization. Pcbp1 has role in tumorigenesis, and metastasis, which are key phenomena of cancer. Role of pcbp2 has been well documented in the biology of RNA virus, namely translation and replication. Here, we studied expression pattern of Pcbp1 and Pcbp2 in three different cancer cell lines namely HeLa, RD, and A375 originated from different tissues. The results indicate not only differential abundance of these two proteins in three cell lines, but also discordant expression of pcbp1 in mRNA and protein level in three cell lines. The study therefore suggests post-transcriptional regulation of pcbp1 expression in these cell lines.