Phototoxic effectiveness of zinc phthalocyanine tetrasulfonic acid on MCF-7 cells with overexpressed P-glycoprotein.

Abstract

The development of multidrug resistance is often associated with the over-expression of P-glycoprotein (P-gp). This protein prevents drug accumulation and extrudes them out of the cell before they reach the intended target. The aim of this study was to develop an in vitro MCF-7 cell line with increased expression of P-gp and test the phototoxicity of a novel photoactivated zinc phthalocyanine tetrasulfonic acid (ZnPcS4) on these cells. The over-expressed P-gp MCF-7 cells (MCF-7/DOX) were developed from wildtype (WT) MCF-7 cells by a stepwise continuous exposure of the WT cells to different concentrations of Doxorubicin (DOX) (0.1 - 1 μM) over a period of 4 months. The P-gp expression was measured using flow cytometry, immunofluorescence and enzyme immunoassay. To verify whether zinc phthalocyanine-mediated photodynamic therapy (ZnPcS4 - PDT) is effective in MCF-7/DOX, we studied the subcellular localization, phototoxicity and nuclear damage. The flow cytometry result showed two distinct peaks of P-gp positive and negative expression in MCF-7/DOX cell population, which correlates with the ELISA-based assay (p˂0.001). The ME16C (Normal breast cells) was used as control. The localization studies showed that ZnPcS4 have greater affinity for lysosome than mitochondria. Phototoxicity results indicated that photoactivated zinc phthalocyanine decreased the cell proliferation and viability as the drug and laser light dosages increased to 16 μM and 20 J/cm2 respectively. PDT-induced cytotoxicity using lactose dehydrogenase (LDH) enzyme leakage as measure did not increase likewise. The ZnPcS4-induced PDT was less effective for MCF-7/DOX cells which could be attributed to decreased retention of ZnPcS4 in major cellular organelles due to the presence of increased drug efflux P-gp. The current findings suggest that, increased P-gp expression, a characteristic of multidrug resistance together with other related intrinsic mechanisms might contribute to render MCF-7/DOX cells less sensitive to ZnPcS4-induced phototoxicity.

• Authors: Aniogo Eric Chekwube, Blassan George, Heidi Abrahamse
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 204 Pg. 111811 (Mar 2020) ISSN: 1873-2682 [Electronic] Switzerland
• PMID: 32028187 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Indoles
• Organometallic Compounds
• Rhodamine 123
• zinc tetrasulfophthalocyanine
• Doxorubicin
• Adenosine Triphosphate

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Adenosine Triphosphate (metabolism)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects, radiation effects)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects, radiation effects)
• Female
• Humans
• Indoles (chemistry, pharmacology)
• Lasers, Semiconductor
• MCF-7 Cells
• Organometallic Compounds (chemistry, pharmacology)
• Photochemotherapy
• Rhodamine 123 (chemistry, metabolism)