Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives

Rouco, Lara; Sánchez-González, Ángeles; Alvariño, Rebeca; Alfonso, Amparo; Vázquez-López, Ezequiel M.; García-Martínez, Emilia; Maneiro, Marcelino

doi:10.3390/ph14010010

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Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives

Lara Rouco

Ángeles Sánchez-González

^2,*

Rebeca Alvariño

^3,*

Amparo Alfonso

Ezequiel M. Vázquez-López

⁴

Emilia García-Martínez

⁴ and

Marcelino Maneiro

^1,*

Departamento de Química Inorgánica, Facultade de Ciencias, Universidade de Santiago de Compostela, 27002 Lugo, Spain

Departamento de Química Inorgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain

Departamento de Farmacología, Facultade de Veterinaria, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain

⁴

Departamento de Química Inorgánica, Facultade de Química, Campus Universitario Lagoas-Marcosende, Universidade de Vigo, 36310 Vigo, Spain

Authors to whom correspondence should be addressed.

Pharmaceuticals 2021, 14(1), 10; https://doi.org/10.3390/ph14010010

Received: 24 November 2020 / Revised: 16 December 2020 / Accepted: 21 December 2020 / Published: 24 December 2020

(This article belongs to the Special Issue Applications of Medicinal Bioinorganic Chemistry)

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Abstract

Since the potential anticancer activity of auranofin was discovered, gold compounds have attracted interest with a view to developing anticancer agents that follow cytotoxic mechanisms other than cisplatin. Two benzimidazole gold(I) derivatives containing triphenylphosphine (Au(pben)(PPh₃)) (1) or triethylphosphine (Au(pben)(PEt₃)) (2) were prepared and characterized by standard techniques. X-ray crystal structures for 1 and 2 were solved. The cytotoxicity of 1 and 2 was tested in human neuroblastoma SH-SY5Y cells. Cells were incubated with compounds for 24 h with concentrations ranging from 10 µM to 1 nM, and the half-maximal inhibitory concentration (IC₅₀) was determined. 1 and 2 showed an IC₅₀ of 2.7 and 1.6 µM, respectively. In order to better understand the type of cell death induced by compounds, neuroblastoma cells were stained with Annexin-FITC and propidium iodide. The fluorescence analysis revealed that compounds were inducing apoptosis; however, pre-treatment with the caspase inhibitor Z-VAD did not reduce cell death. Analysis of compound effects on caspase-3 activity and reactive oxygen species (ROS) production in SH-SY5Y cells revealed an antiproliferative ability mediated through oxidative stress and both caspase-dependent and caspase-independent mechanisms. View Full-Text

Keywords: gold(I) compounds; cytotoxic activity; caspase; apoptosis; neuroblastoma SH-SY5Y

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Rouco, L.; Sánchez-González, Á.; Alvariño, R.; Alfonso, A.; Vázquez-López, E.M.; García-Martínez, E.; Maneiro, M. Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives. Pharmaceuticals 2021, 14, 10. https://doi.org/10.3390/ph14010010

AMA Style

Rouco L, Sánchez-González Á, Alvariño R, Alfonso A, Vázquez-López EM, García-Martínez E, Maneiro M. Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives. Pharmaceuticals. 2021; 14(1):10. https://doi.org/10.3390/ph14010010

Chicago/Turabian Style

Rouco, Lara, Ángeles Sánchez-González, Rebeca Alvariño, Amparo Alfonso, Ezequiel M. Vázquez-López, Emilia García-Martínez, and Marcelino Maneiro. 2021. "Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives" Pharmaceuticals 14, no. 1: 10. https://doi.org/10.3390/ph14010010

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Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives

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