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Impact of extracellular alkalinization on the survival of human CD24-/CD44+ breast cancer stem cells associated with cellular metabolic shifts
Wanandi, SI; Yustisia, I; Neolaka, GMG; Jusman, SWA.
  • Wanandi, SI; Universitas Indonesia. Faculty of Medicine. Department of Biochemistry and Molecular Biology. Jakarta. ID
  • Yustisia, I; Universitas Indonesia. Faculty of Medicine. Department of Biochemistry and Molecular Biology. Jakarta. ID
  • Neolaka, GMG; Universitas Indonesia. Faculty of Medicine. Department of Biochemistry and Molecular Biology. Jakarta. ID
  • Jusman, SWA; Universitas Indonesia. Faculty of Medicine. Department of Biochemistry and Molecular Biology. Jakarta. ID
Braz. j. med. biol. res ; 50(8): e6538, 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-888984
ABSTRACT
Cancer stem cells reside in a distinct region within the tumor microenvironment that it is believed to play a fundamental role in regulating stemness, proliferation, survival, and metabolism of cancer cells. This study aimed to analyze the effect of extracellular alkalinization on metabolism and survival of human CD24-/CD44+ breast cancer stem cells (BCSCs). BCSCs were cultured in alkalinized DMEM-F12 and incubated at 37°C, 5% CO2, and 20% O2 for 30 min, 6, 24, and 48 h. After each incubation period, we analyzed the modulation of various mRNA expressions related to pH and cellular metabolic regulation using the qRT-PCR. Metabolic state was measured using colorimetric and fluorometric assays. To examine cell proliferation and apoptosis, we used trypan blue and annexin V/propidium iodide assay, respectively. This study demonstrated that alkalinization could stimulate extracellular carbonic anhydrase (CAe) activity, as well as CA9 and HIF1α expression. Under alkaline pH and HIF1α regulation, glucose consumption, extracellular lactate production, and LDH activity of BCSCs were upregulated while O2 consumption was downregulated. These metabolic shifts seemed to promote apoptosis and suppress the proliferation of BCSCs. To conclude, modulation of the extracellular environment through alkalinization could change the metabolic states of BCSCs, which in turn affect the cell survival.
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Texto completo: Disponible Índice: LILACS (Américas) Asunto principal: Células Madre Neoplásicas / Neoplasias de la Mama / Receptores de Hialuranos / Antígeno CD24 Tipo de estudio: Factores de riesgo Límite: Femenino / Humanos Idioma: Inglés Revista: Braz. j. med. biol. res Asunto de la revista: Biologia / Medicina Año: 2017 Tipo del documento: Artículo País de afiliación: Indonesia Institución/País de afiliación: Universitas Indonesia/ID

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Texto completo: Disponible Índice: LILACS (Américas) Asunto principal: Células Madre Neoplásicas / Neoplasias de la Mama / Receptores de Hialuranos / Antígeno CD24 Tipo de estudio: Factores de riesgo Límite: Femenino / Humanos Idioma: Inglés Revista: Braz. j. med. biol. res Asunto de la revista: Biologia / Medicina Año: 2017 Tipo del documento: Artículo País de afiliación: Indonesia Institución/País de afiliación: Universitas Indonesia/ID