The A2b adenosine receptor antagonist PSB-603 promotes oxidative phosphorylation and ROS production in colorectal cancer cells via adenosine receptor-independent mechanism.
Cancer Lett
; 383(1): 135-143, 2016 12 01.
Article
en En
| MEDLINE
| ID: mdl-27693637
ABSTRACT
PURPOSE:
Adenosine is a multifaceted regulator of tumor progression. It modulates immune cell activity as well as acting directly on tumor cells. The A2b adenosine receptor (A2b-AR) is thought to be an important mediator of these effects. In this study we sought to analyze the contribution of the A2b-AR to the behavior of colorectal cancer cells. PRINCIPALRESULTS:
The A2b-AR antagonist PSB-603 changed cellular redox state without affecting cellular viability. Quantification of cellular bioenergetics demonstrated that PSB-603 increased basal oxygen consumption rates, indicative of enhanced mitochondrial oxidative phosphorylation. Unexpectedly, pharmacological and genetic approaches to antagonize AR-related signalling of PSB-603 did not abolish the response, suggesting that it was AR-independent. PSB-603 also induced acute increases in reactive oxygen species, and PSB-603 synergized with chemotherapy treatment to increase colorectal cancer cell death, consistent with the known link between cellular metabolism and chemotherapy response. MAJORCONCLUSIONS:
PSB-603 alters cellular metabolism in colorectal cancer cells and increases their sensitivity to chemotherapy. Although requiring more mechanistic insight into its A2b-AR-independent activity, our results show that PSB-603 may have clinical value as an anti-colorectal cancer therapeutic.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_colon_rectum_cancers
Asunto principal:
Fosforilación Oxidativa
/
Sulfonamidas
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Xantinas
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Neoplasias Colorrectales
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Especies Reactivas de Oxígeno
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Estrés Oxidativo
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Receptor de Adenosina A2B
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Antagonistas del Receptor de Adenosina A2
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Mitocondrias
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2016
Tipo del documento:
Article
País de afiliación:
Australia