New Hydrophilic/Lipophilic Tetra-α-(4-carboxyphenoxy) Phthalocyanine Zinc-Mediated Photodynamic Therapy Inhibits the Proliferation of Human Hepatocellular Carcinoma Bel-7402 Cells by Triggering Apoptosis and Arresting Cell Cycle

Abstract

Photodynamic therapy (PDT) is a novel and promising antitumor treatment. Phthalocyanine-mediated PDT has shown antitumor activity in some tumor cells, but the effect of new hydrophilic/lipophilic tetra-α-(4-carboxyphenoxy)phthalocyanine zinc (TαPcZn)-mediated PDT (TαPcZn-PDT) on human hepatocellular carcinoma Bel-7402 cells and underlying mechanisms have not been clarified. In the present study, therefore, the ultraviolet-visible (UV-vis) absorption spectrum and cellular localization of TαPcZn, and effect of TαPcZn-PDT on the proliferation, apoptosis, cell cycle, Bcl-2 and Fas in Bel-7402 cells were investigated by spectrophotometry, inverted microscope, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, electron microscopy, annexinV-FITC/propidium iodide double staining, DNA content and immunoblot assay, respectively. We found that an intense absorption in UV-vis absorption spectrum of TαPcZn was in the red visible region at 650-680 nm, where light penetration in tissue is efficient, that green TαPcZn localized to both plasma membrane and nuclear membrane of 1390Bel-7402 cells, signifying that there was a selective uptake of TαPcZn in Bel-7402 cells and TαPcZn-PDT would be expected to directly damage DNA, and that TαPcZn-PDT significantly resulted in the proliferation inhibition, apoptosis induction, S cell cycle arrest, and down-regulation of Bcl-2 and Fas. Taken together, we conclude that TαPcZn-PDT inhibits the proliferation of Bel-7402 cells by triggering apoptosis and arresting the cell cycle.

p53‐Dependent and p53‐Independent Responses of Cells Challenged by Photosensitization

“…Interestingly, we also made a new observation concerning the effects induced by DMMB/light treatment: There is a clear cell cycle arrest at S phase in the cell lines, in accordance with the results of other studies using different cells and photosensitizers (26,46,47). Our data also indicate that accumulation of cells in S phase was not affected by the expression level of p53 protein, as had been previously reported for HCT116 cells treated with hypericin (26).…”

Apoptosis induced by ZnPcH1-based photodynamic therapy in Jurkat cells and HEL cells

“…The killing effect of PDT on tumor cells results largely from the induction of apoptosis [8][9][10]. The acting mechanism of PDT treatment varies depending on the applied photosensitizers and target cell types.…”

Autoregulatory Feedback Mechanism of P38MAPK/Caspase-8 in Photodynamic Therapy-Hydrophilic/Lipophilic Tetra-α-(4-carboxyphenoxy) Phthalocyanine Zinc-Induced Apoptosis of Human Hepatocellular Carcinoma Bel-7402 Cells

“…In addition, phthalocyanines with hydrophilic/lipophilic structure may become promising candidates for selectivephotosensitizers inasmuch as hydrophilic group contributes to the 2 International Journal of Photoenergy transport of drug in the body and lipophilic group redounds to the uptake of drug in cancer cells. Accumulating evidences have shown highly selective growth inhibitory effects of hydrophilic/lipophilic phthalocyanines-mediated PDT on a variety of cancer cells [11][12][13].…”

“…Apoptosis is characterized by morphologic and biochemical changes including chromatin condensation, cell shrinkage, nucleus and cytoplasm fragment, DNA fragmentation, and formation of membrane blebs and apoptotic bodies. Accumulating evidences clearly indicate that apoptosis is one key pathway in phthalocyanines-PDT process [11][12][13].…”

“…molecules. Recent studies have demonstrated that induction of proapoptotic proteins and inhibition of antiapoptotic proteins can be caused by phthalocyanines-PDT in apoptosis of cancer cells [11,21,22].…”