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2019•Breast Cancer ManagementOpen access

Diltiazem Potentiation of Doxorubicin Cytotoxicity and Cellular Uptake in Human Breast Cancer Cells

Hamdan S. Al-malky, Zoheir A. Damanhouri, Jumana Y Al Aama, Ali A. Al Qahtani, Wafaa S. Ramadan, Huda Mohammed Alkreathy, Sameer E Al Harthi, Abdel‐Moneim M. Osman

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Abstract

Aim: Breast cancer is the most common cancer among Arab women and also around the world. Chronic cardiotoxicity and multidrug resistance are potential limiting factors of doxorubicin (DOX), a known anthracycline antibiotic. Materials & methods: DOX cytotoxicity was evaluated by the sulforhodamine method. DOX cellular uptake, detection of P-glycoprotein activity and the photomicrograph of MCF-7 cells were also determined. Results: Diltiazem (DIL) treatment improved DOX cytotoxic activity and increased the cellular uptake of DOX significantly and aggregation of rhodamine 123, reflecting inhibition of P-glycoprotein pump. Cytopathological investigation of MCF-7 cells revealed marked cytotoxic activity of DOX in the presence of DIL. Conclusion: DIL treatment enhanced DOX cytotoxic effect and reduced multidrug resistance, which increased the drug accumulation intracellularly.

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Aim: Breast cancer is the most common cancer among Arab women and also around the world. Chronic cardiotoxicity and multidrug resistance are potential limiting factors of doxorubicin (DOX), a known anthracycline antibiotic. Materials & methods: DOX cytotoxicity was evaluated by the sulforhodamine method. DOX cellular uptake, detection of P-glycoprotein activity and the photomicrograph of MCF-7 cells were also determined. Results: Diltiazem (DIL) treatment improved DOX cytotoxic activity and increased the cellular uptake of DOX significantly and aggregation of rhodamine 123, reflecting inhibition of P-glycoprotein pump. Cytopathological investigation of MCF-7 cells revealed marked cytotoxic activity of DOX in the presence of DIL. Conclusion: DIL treatment enhanced DOX cytotoxic effect and reduced multidrug resistance, which increased the drug accumulation intracellularly.

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Available abstract

Aim: Breast cancer is the most common cancer among Arab women and also around the world. Chronic cardiotoxicity and multidrug resistance are potential limiting factors of doxorubicin (DOX), a known anthracycline antibiotic. Materials & methods: DOX cytotoxicity was evaluated by the sulforhodamine method. DOX cellular uptake, detection of P-glycoprotein activity and the photomicrograph of MCF-7 cells were also determined. Results: Diltiazem (DIL) treatment improved DOX cytotoxic activity and increased the cellular uptake of DOX significantly and aggregation of rhodamine 123, reflecting inhibition of P-glycoprotein pump. Cytopathological investigation of MCF-7 cells revealed marked cytotoxic activity of DOX in the presence of DIL. Conclusion: DIL treatment enhanced DOX cytotoxic effect and reduced multidrug resistance, which increased the drug accumulation intracellularly.

Key concepts: Doxorubicin, Cytotoxicity, Pharmacology, Rhodamine 123, Cytotoxic T cell, Diltiazem, Medicine, P-glycoprotein

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Diltiazem Potentiation of Doxorubicin Cytotoxicity and Cellular Uptake in Human Breast Cancer Cells — Research Paper | ScholarLens