Phototoxic action of a zinc(II) phthalocyanine encapsulated into poloxamine polymeric micelles in 2D and 3D colon carcinoma cell cultures

Chiarante, Nicolás; Vior, María C. García; Awruch, Josefina; Marino, Julieta; Roguin, Leonor P.

doi:10.1016/j.jphotobiol.2017.04.009

Cited by 22 publications

(25 citation statements)

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“…3A). To further corroborate this observation, the cells were incubated in the presence of 5 mM TROLOX, an antioxidant concentration previously reported to protect cells from the phototoxic effect of Pc9-T1107 (Chiarante et al, 2017). As shown in Fig.…”

Section: Pc9-t1107 Affects Lysosomal Membrane Stabilitymentioning

confidence: 56%

“…Tetronic® 1107 polymeric poloxamine micelles exerted an effective phototoxic activity both in 2D and 3D cultures of murine colon carcinoma CT26 cells (Chiarante et al, 2017). We further demonstrated that after localizing into lysosome vesicles and ER cisterns, Pc9-T1107…”

Section: Accepted Manuscriptmentioning

confidence: 64%

“…We have previously showed that the photoactivation of the lipophilic phthalocyanine Pc9 encapsulated into T1107 polymeric micelles induced a caspase 3-dependent apoptotic cell death both in 2D and 3D cultures of colon carcinoma CT26 cells (Chiarante et al, 2017).…”

Section: Pc9-t1107 Treatment Arrests Cell Cycle and Regulates Mitochomentioning

confidence: 98%

“…promotes an apoptotic response (Chiarante et al, 2017). Herein, we explored the contribution of the intracellular signals triggered after PDT to the activation of an apoptotic program in colon cancer-derived cells.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…In a previous study, we demonstrated that Pc9-T1107 localizes mainly into lysosomal vesicles and ER cisterns in CT26 cells and that Pc9-T1107 induced the generation of ROS immediately after cell irradiation (Chiarante et al, 2017). In order to gain a better understanding of the molecular mechanisms mediating the cell death by Pc9-T1107, we examined the biological effects triggered by ROS formation in the intracellular organelles retaining Pc9-T1107.…”

Section: Pc9-t1107 Affects Lysosomal Membrane Stabilitymentioning

confidence: 99%

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Lysosomal permeabilization and endoplasmic reticulum stress mediate the apoptotic response induced after photoactivation of a lipophilic zinc(II) phthalocyanine

Chiarante

Vior

Rey

et al. 2018

The International Journal of Biochemistry & Cell Biology

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We have previously reported that the phototoxic action of the lipophilic phthalocyanine Pc9 (2,9(10),16(17),23(24) tetrakis[(2-dimethylamino)ethylsulfanyl]phthalocyaninatozinc(II)) encapsulated into poloxamine micelles is related to the induction of an apoptotic response in murine colon CT26 carcinoma cells. In the present study, we explored the intracellular signals contributing to the resulting apoptotic death. We found that Pc9-T1107 arrests cell cycle progression immediately after irradiation promoting then an apoptotic response. Thus, 3 h after irradiation the percentage of hypodiploid cells increased from 5.9 ± 0.6% to 23.1 ± 0.1%; activation of caspases 8 and 9 was evident; the population of cells with loss of mitochondrial membrane potential increased from 1.1 ± 0.4% to 44.0 ± 9.3%; the full-length forms of Bid and PARP-1 were cleaved; and a 50% decrease of the expression levels of the anti-apoptotic proteins Bcl-2 and Bcl-X was detected. We also found that the photosensitizer, mainly retained in lysosomes and endoplasmic reticulum (ER), promotes the permeabilization of lysosomal membranes and induces ER stress. Lysosomal membrane permeabilization was demonstrated by the reduction of acridine orange lysosome fluorescence, the release of Cathepsin D into the cytosol and ∼50% decrease of Hsp70, a chaperone recognized as a lysosomal stabilizer. Cathepsin D also contributed to Bid cleavage and caspase 8 activation. The oxidative damage to the ER induced an unfolded protein response characterized, 3 h after irradiation, by a 3-fold increase in cytosolic Ca levels and 3-4 times higher expression of ER chaperones GRP78/BIP, calnexin, Hsp90 and Hsp110. The cell death signaling promoted by cytosolic Ca, calpains and lysosomal proteases was partially abolished by the Ca chelator BAPTA-AM, the calpain inhibitor PD 150606 and proteases inhibitors. Furthermore, Bax down-regulation observed in Pc9-treated cells was undetectable in the presence of PD 150606, indicating that calpains contribute to Bax proteolytic damage. In summary, our results indicate that photoactivation of Pc9-T1107 led to lysosomal membrane permeabilization, induction of ER stress and activation of a caspase-dependent apoptotic cell death.

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Section: Pc9-t1107 Affects Lysosomal Membrane Stabilitymentioning

confidence: 56%

Section: Accepted Manuscriptmentioning

confidence: 64%

Section: Pc9-t1107 Treatment Arrests Cell Cycle and Regulates Mitochomentioning

confidence: 98%

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Pc9-t1107 Affects Lysosomal Membrane Stabilitymentioning

confidence: 99%

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