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Synergistic induction of apoptosis in liver cancer cells: exploring the combined potential of doxorubicin and XL-888

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Abstract

Combination therapy has been frequently preferred in treating various types of cancer in recent years. Targeted cancer therapy has also become one of the remarkable treatment modalities. Therefore, the aim of the study to investigate its cytotoxic and apoptotic effects on liver cancer cell lines by combining the classical chemotherapeutic drug doxorubicin (DOX) and a targeted agent, the new generation HSP90 inhibitor XL-888. The molecular docking method was used to predict the binding conformation of XL-888 on the human Hsp90. The single and combined cytotoxic effects of DOX and XL-888 on liver cancer cell lines HepG2 and HUH-7 were determined by MTT assay. The effect of the combined use of two drugs was evaluated using Chou and Talalay method. The levels of apoptotic genes and heat shock proteins gene and protein expression levels were investigated by quantitative real-time polymerase chain reaction and western blotting, respectively. Molecular docking results showed that XL-888 selectively binds to the ATP binding pocket of HSP90 with an estimated free binding energy of − 7.8 kcal/mol. DOX and XL-888 and their combination showed dose-dependent cytotoxic effect. The combination of drugs showed a synergistic effect on both cell lines. The results revealed that the combination of DOX and XL-888 potently induced apoptosis in liver cancer cell lines rather than using drugs alone. The combined treatment of DOX and XL-888 demonstrated synergistic cytotoxic and apoptotic effects on liver cancer cell lines, presenting a promising approach for combination therapy in liver cancer.

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Data and materials are available from the author upon request.

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Acknowledgements

The author would like to thank Prof. Dr. İsa Gökçe and Dr. Nazan Gökşen Tosun for contributions.

Funding

No support was received in this study. However, the facilities of Tokat Gaziosmanpasa University, Faculty of Engineering and Architecture, Department of Bioengineering laboratories were used.

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  1. Department of Genetics and Bioengineering, Rafet Kayış Faculty of Engineering, Alanya Alaaddin Keykubat University, Antalya, Turkey

    Özlem Kaplan

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Kaplan, Ö. Synergistic induction of apoptosis in liver cancer cells: exploring the combined potential of doxorubicin and XL-888. Med Oncol 40, 318 (2023). https://doi.org/10.1007/s12032-023-02181-9

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