Teraphtal (sodium salt of cobalt 4,5-carboxyphthalocyanine) Decreases Sensitivity of Tumor Cells to Anthracycline Antibiotics and Mitoxantrone in Vitro

EXPERIMENTAL STUDIES , , , , , ,

TA Sidorova1, OO Ryabaya1, VV Tatarskii1, DA Khochenkov1, ES Ivanova1, OL Kaliya2

1 NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 State Research Center NIOPIC, 1 bld. 4 B. Sadovaya str., Moscow, Russian Federation, 123995

For correspondence: Tat’yana Aleksandrovna Sidorova, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: tatsid@yahoo.com

For citation: Sidorova TA, Ryabaya ОО, Tatarskii VV, et al. Teraphtal (sodium salt of cobalt 4,5-carboxyphthalocyanine) Decreases Sensitivity of Tumor Cells to Anthracycline Antibiotics and Mitoxantrone in Vitro. Clinical oncohematology. 2018;11(1):10–25.

DOI: 10.21320/2500-2139-2018-11-1-10-25

ABSTRACT

Background. Anthracycline antibiotics (AA) are widely used in clinical oncohematology. As is well known АА cytotoxicity diminishes in the presence of hemin (FePPIX), an endogenous metalloporphyrine.

Aim. To study effect of teraphtal (TPh) and its structural analog FePPIX on cytotoxicity of “anthraquinone” drugs AA and mitoxantrone (MiTOX) in vitro.

Materials & Methods. The study was performed using human leukemia cells of K562 line and HCT 116 adenocarcinoma cell line. TPh ability to prevent AA-induced tumor cell death has been estimated by the following methods: MTT assays, flow cytometry, light microscopy, cytochemical method for determination of b-galactosidase expression using X-Gal substrate, DNA electrophoresis, LDH release, real time RT-PCR, and radiometric method.

Results. In the presence of TPh (10 µM) the AA and MiTOX cytotoxicity diminishes approximately 4- and 20-fold respectively. The TPh protective potency is dependent on the AA chemical structure. In the presence of TPh aclarubicin toxicity remains constant. The TPh/FePPIX protection from the AA cytotoxicity can involve the same mechanism reducing the ability of the cells, including the leukemia tumor cells, to accumulate AA in the presence of modulators. TPh/FePPIX protects human tumor cells from AA-induced death, such as apoptosis, necrosis, and accelerated senescence (АS). АS in K562 leukemia cell line induced by AA + TPh/FePPIX results in cell-suspension-derived-small-cell colonies. Вeclin-lysosomal pathway of autophagy is not engaged in reducing of the AA toxicity of K562 cells in the presence of TPh.

Conclusion. Reducing of the AA toxicity and revival of cell population growth in the presence of TPh/FePPIX should be taken into consideration when using hematoporphyrins and phthalocyanines having a structure similar to TPh as sensitizers in the chemotherapy protocols.

Keywords: anthracycline antibiotics, mitoxantrone, teraphtal, hemin, human tumor cells, drug induced senescence, autophagy.

Received: July 2, 2017

Accepted: November 13, 2017

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