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Cytotoxic effects of two organotin compounds and their mode of inflicting cell death on four mammalian cancer cells

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Abstract

In this report, we have tested the cytotoxicity of two organotin (OT) compounds by flow cytometry on a panel of immortalized cancer cell lines of human and murine origin. Although the OT compounds exhibited varying levels of cytotoxicity, diphenylmethyltin chloride was more toxic than 1,4-bis (diphenylchlorostannyl)p-xylene on all cell lines tested. The OT compounds were found to be highly cytotoxic to lymphoma cell lines with lower toxicity toward the HeLa cervical cancer cell line. In order to discern the mechanism by which cell death was induced, additional experiments were conducted to monitor characteristic changes consistent with apoptosis and/or necrosis. Cell lines treated with the experimental compounds indicated that there was no consistent mode of cell death induction. However, both compounds induced apoptosis in the pro-B lymphocyte cell line, NFS-70. The work presented here also demonstrates that the two OT compounds possess selective cytotoxicity against distinct transformed cell lines.

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Abbreviations

ATCC:

American Type Culture Collection

Bis(Ph2SnCl)Xylene:

1,4-Bis (diphenylchlorostannyl)p-xylene

CC50 :

Concentration that results in 50% cytotoxicity

DBT:

Di-n-butyltin chloride

DMEM:

Dulbecco’s modified Eagle medium

DMSO:

Dimethyl sulfoxide

DPMT:

Diphenylmethyltin chloride

EDTA:

Ethylenediaminetetraacetic acid

FACS:

Fluorescence-activated cell sorter

FITC:

Fluorescein isothiocyanate

H2O2 :

Hydrogen peroxide

ID50 :

The 50% inhibitory dose

IL-2:

Interleukin-2

NK:

Natural killer

OT:

Organotin

PBS:

Phosphate buffered saline

PI:

Propidium iodide

PS:

Phosphatidylserine

PVC:

Polyvinyl chloride

ROS:

Reactive oxygen species

RPMI:

Roswell Park Memorial Institute

TBT:

Tri-n-butyltin chloride

TMT:

Trimethyltin

TPT:

Triphenyltin

TPT-CuCl2 :

Triphenyltin benzimidazolethiol copper chloride

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Acknowledgments

The authors thank Dr. S. Nagy for the generous gift of the Kit 225 cell line and to the staff of the UTEP’s Cell Culture and High Throughput Screening Core Facility for services and facilities provided. This work was supported by grant 5G12RR008124 to the Border Biomedical Research Center, granted to the University of Texas at El Paso from the National Center for Research Resources of the NIH. Y.P.C. was supported by the NIH-MARC*USTAR (5T34GM008048-25) and RISE (R25 GM069621-07) programs. Also, the authors thank Drs. Julia Bader for statistic analysis and Carolina Lema for critically reading the manuscript and help with organizing the bibliography.

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Authors and Affiliations

  1. Department of Biological Sciences, Biosciences Research Building, University of Texas at El Paso, 500 West University Ave., El Paso, TX, 79968-5816, USA

    Armando Varela-Ramirez, Margaret Costanzo & Renato J. Aguilera

  2. Chemistry Department, University of Texas at El Paso, 500 West University Ave., El Paso, TX, 79902-5816, USA

    Yazmin P. Carrasco & Keith H. Pannell

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  1. Armando Varela-Ramirez
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  2. Margaret Costanzo
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  3. Yazmin P. Carrasco
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  4. Keith H. Pannell
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  5. Renato J. Aguilera
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Correspondence to Armando Varela-Ramirez.

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Varela-Ramirez, A., Costanzo, M., Carrasco, Y.P. et al. Cytotoxic effects of two organotin compounds and their mode of inflicting cell death on four mammalian cancer cells. Cell Biol Toxicol 27, 159–168 (2011). https://doi.org/10.1007/s10565-010-9178-y

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