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. 2011 Feb 7;16(2):1389-401.
doi: 10.3390/molecules16021389.

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

Chunhui Xia  1 , Yu Wang, Wei Chen, Wenxue Yu, Baiqi Wang, Tao Li
Affiliations

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

Chunhui Xia et al. Molecules. .

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 Bel-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.

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Figures

Figure 1
Figure 1
Chemical structure of TαPcZn.
Figure 2
Figure 2
UV-vis absorption spectra of TαPcZn in DMSO/water (1:3, v/v) mixtures.
Figure 3
Figure 3
Effect of TαPcZn-PDT on the proliferation of Bel-7402 cells and HDFs. Proliferation of Bel-7402 cells and HDFs analyzed by MTT assay. Bel-7402 cells and HDFs were treated with the different concentrations of TαPcZn in the presence of red-light irradiation (53.7 J/cm2). Cell viability was detected by MTT assay. P < 0.01 versus the control value (cells treated with 0.1% DMSO).
Figure 4
Figure 4
Effect of TαPcZn-PDT on Bel-7402 cells morphology. (A) Bel-7402 cells morphology analyzed by inverted microscope. Bars under each panel represent 50 um. (B) Bel-7402 cells morphology analyzed by Electron microscopy. Bars under each panel represent 500 nm. Morphology assay in: panel A1 or B1, control Bel-7402 cells treated with 0.1% DMSO; panel A2 or B2, Bel-7402 cells treated with red-light irradiation (53.7 J/cm2); panel A3 or B3, Bel-7402 cells treated with 54 μM TαPcZn; and panel A4 or B4, Bel-7402 cells treated with 54 μM TαPcZn in the presence of red-light irradiation (53.7 J/cm2).
Figure 5
Figure 5
Effect of TαPcZn-PDT on the apoptosis of Bel-7402 cells assayed by flow cytometry analysis of Annexin V-FITC/PI double stained cells. Apoptosis assay in: panel A, control Bel-7402 cells treated with 0.1% DMSO; panel B, Bel-7402 cells treated with red-light irradiation (53.7 J/cm2); panel C, Bel-7402 cells treated with 54 μM TαPcZn; and panel D~F, Bel-7402 cells treated with 18, 36, 54 μM TαPcZn in the presence of red-light irradiation(53.7 J/cm2), respectively.
Figure 6
Figure 6
Effect of TαPcZn-PDT on the cycle and apoptosis of Bel-7402 cells assayed by flow cytometry analysis of DNA content. Assay of cycle and apoptosis in: panel A, control Bel-7402 cells treated with 0.1% DMSO; panel B, Bel-7402 cells treated with red-light irradiation (53.7 J/cm2); panel C, Bel-7402 cells treated with 54 μM TαPcZn; and panel D, Bel-7402 cells treated with 54 μM TαPcZn in the presence of red-light irradiation (53.7 J/cm2).
Figure 7
Figure 7
Effect of TαPcZn-PDT on Bcl-2 and Fas respectively in TαPcZn-PDT-induced apoptosis of Bel-7402 cells analyzed by Immunoblot assay. Expression of Bcl-2 and Fas in: Lane 1, control Bel-7402 cells treated with 0.1% DMSO; Lane 2, Bel-7402 cells treated with red-light irradiation (53.7 J/cm2); Lane 3, Bel-7402 cells treated with 54 μM TαPcZn; and Lane 4~6, Bel-7402 cells treated with 18, 36, 54 μM TαPcZn in the presence of red-light irradiation(53.7 J/cm2), respectively.
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