The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells

Takács, Angéla; Szász, Zsófia; Kalabay, Márton; Bárány, Péter; Csámpai, Antal; Hegyesi, Hargita; Láng, Orsolya; Lajkó, Eszter; Kőhidai, László

doi:10.3390/ph14080820

Open AccessArticle

The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells

by

Angéla Takács

^1,†,

Zsófia Szász

^1,†,

Márton Kalabay

¹,

Péter Bárány

²,

Antal Csámpai

²

,

Hargita Hegyesi

¹,

Orsolya Láng

¹,

Eszter Lajkó

¹

and

László Kőhidai

^1,*

¹

Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Hungary

²

Department of Organic Chemistry, Institute of Chemistry, Eötvös Loránd University, H-1117 Budapest, Hungary

^*

Author to whom correspondence should be addressed.

^†

These authors as first authors contributed equally to this work.

Pharmaceuticals 2021, 14(8), 820; https://doi.org/10.3390/ph14080820

Submission received: 29 June 2021 / Revised: 6 August 2021 / Accepted: 17 August 2021 / Published: 20 August 2021

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Abstract

Combination antitumor treatments are essential parts of modern tumor therapy as—compared to monotherapies—(i) they are more effective; (ii) the dose of the compounds can be reduced; and (iii) therefore the side effects are improved. Our research group previously demonstrated the antitumor character of bortezomib (BOZ) in A2058 melanoma cells. Unfortunately, dose-related side effects are common during BOZ therapy, which could be prevented by reducing the dose of BOZ. This study aimed to characterize synergistic combinations of BOZ with a TRAIL (TNF-related apoptosis-inducing ligand) -inducing compound (TIC10), where the doses can be cut down but the efficacy is preserved. Endpoint cell viability assays were performed on A2058 cells, and synergism of BOZ and TIC10 was observed after 72 h. Synergism was further validated in a real-time impedimetric assay, and our results showed that BOZ-treated melanoma cells survived the treatment, an effect not registered in the co-treatments. Treatment with the combinations resulted in increased apoptosis, which was not accompanied by enhanced LDH release. Nevertheless, the expression of death receptor 5 (DR5) was increased on the cell surface without transcriptional regulation. In summary, our findings support the theory that the application of BOZ and TIC10 in combination could provide higher efficacy in vitro.

Keywords: combination therapy; bortezomib; TIC10; antitumor efficacy; melanoma

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MDPI and ACS Style

Takács, A.; Szász, Z.; Kalabay, M.; Bárány, P.; Csámpai, A.; Hegyesi, H.; Láng, O.; Lajkó, E.; Kőhidai, L. The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells. Pharmaceuticals 2021, 14, 820. https://doi.org/10.3390/ph14080820

AMA Style

Takács A, Szász Z, Kalabay M, Bárány P, Csámpai A, Hegyesi H, Láng O, Lajkó E, Kőhidai L. The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells. Pharmaceuticals. 2021; 14(8):820. https://doi.org/10.3390/ph14080820

Chicago/Turabian Style

Takács, Angéla, Zsófia Szász, Márton Kalabay, Péter Bárány, Antal Csámpai, Hargita Hegyesi, Orsolya Láng, Eszter Lajkó, and László Kőhidai. 2021. "The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells" Pharmaceuticals 14, no. 8: 820. https://doi.org/10.3390/ph14080820

APA Style

Takács, A., Szász, Z., Kalabay, M., Bárány, P., Csámpai, A., Hegyesi, H., Láng, O., Lajkó, E., & Kőhidai, L. (2021). The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells. Pharmaceuticals, 14(8), 820. https://doi.org/10.3390/ph14080820

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The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells

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