CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis

CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis

Abstract Background/aims: Hypoxia microenvironment plays a crucial role during tumor progression and it tends to exhibit poor prognosis and make resistant to various conventional therapies. HIF-1α acts as an important transcriptional regulator directly or indirectly associated with genes i...

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Autores principales: Rana,Nishant Kumar, Singh,Priya, Koch,Biplob
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2019
Materias:
Hypoxia
Apoptosis
CoCl2
HIF-1α
VEGF
p53
BAX
Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100210
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spelling oai:scielo:S0716-976020190001002102019-10-10CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosisRana,Nishant KumarSingh,PriyaKoch,Biplob Hypoxia Apoptosis CoCl2 HIF-1α VEGF p53 BAX Abstract Background/aims: Hypoxia microenvironment plays a crucial role during tumor progression and it tends to exhibit poor prognosis and make resistant to various conventional therapies. HIF-1α acts as an important transcriptional regulator directly or indirectly associated with genes involved in cell proliferation, angiogenesis, apoptosis and energy metabolism during tumor progression in hypoxic microenvironment. This study was aimed to investigate the expression pattern of the hypoxia associated genes and their association during breast cancer progression under hypoxic microenvironment in breast cancer cells. Methods: Cell proliferation in MCF-7 and MDA-MB-231 cell lines treated with different concentration of CoCl2 was analyzed by MTT assay. Flow cytometry was performed to check cell cycle distribution, whereas cell morphology was examined by phase contrast microscopy in both the cells during hypoxia induction. Expression of hypoxia associated genes HIF-1α, VEGF, p53 and BAX were determined by semiquantitative RT-PCR and real-time PCR. Western blotting was performed to detect the expression at protein level. Results: Our study revealed that cell proliferation in CoCl2 treated breast cancer cells were concentration dependent and varies with different cell types, further increase in CoCl2 concentration leads to apoptotic cell death. Further, accumulation of p53 protein in response to hypoxia as compare to normoxia showed that induction of p53 in breast cancer cells is HIF-1α dependent. HIF-1α dependent BAX expression during hypoxia revealed that after certain extent of hypoxia induction, over expression of BAX conquers the effect of anti-apoptotic proteins and ultimately leads to apoptosis in breast cancer cells. Conclusion: In conclusion our results clearly indicate that CoCl2 simulated hypoxia induce the accumulation of HIF-1α protein and alter the expression of hypoxia associated genes involved in angiogenesis and apoptosis.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.52 20192019-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100210en10.1186/s40659-019-0221-z
institution Scielo Chile
collection Scielo Chile
language English
topic Hypoxia
Apoptosis
CoCl2
HIF-1α
VEGF
p53
BAX
spellingShingle Hypoxia
Apoptosis
CoCl2
HIF-1α
VEGF
p53
BAX
Rana,Nishant Kumar
Singh,Priya
Koch,Biplob
CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis
description Abstract Background/aims: Hypoxia microenvironment plays a crucial role during tumor progression and it tends to exhibit poor prognosis and make resistant to various conventional therapies. HIF-1α acts as an important transcriptional regulator directly or indirectly associated with genes involved in cell proliferation, angiogenesis, apoptosis and energy metabolism during tumor progression in hypoxic microenvironment. This study was aimed to investigate the expression pattern of the hypoxia associated genes and their association during breast cancer progression under hypoxic microenvironment in breast cancer cells. Methods: Cell proliferation in MCF-7 and MDA-MB-231 cell lines treated with different concentration of CoCl2 was analyzed by MTT assay. Flow cytometry was performed to check cell cycle distribution, whereas cell morphology was examined by phase contrast microscopy in both the cells during hypoxia induction. Expression of hypoxia associated genes HIF-1α, VEGF, p53 and BAX were determined by semiquantitative RT-PCR and real-time PCR. Western blotting was performed to detect the expression at protein level. Results: Our study revealed that cell proliferation in CoCl2 treated breast cancer cells were concentration dependent and varies with different cell types, further increase in CoCl2 concentration leads to apoptotic cell death. Further, accumulation of p53 protein in response to hypoxia as compare to normoxia showed that induction of p53 in breast cancer cells is HIF-1α dependent. HIF-1α dependent BAX expression during hypoxia revealed that after certain extent of hypoxia induction, over expression of BAX conquers the effect of anti-apoptotic proteins and ultimately leads to apoptosis in breast cancer cells. Conclusion: In conclusion our results clearly indicate that CoCl2 simulated hypoxia induce the accumulation of HIF-1α protein and alter the expression of hypoxia associated genes involved in angiogenesis and apoptosis.
author Rana,Nishant Kumar
Singh,Priya
Koch,Biplob
author_facet Rana,Nishant Kumar
Singh,Priya
Koch,Biplob
author_sort Rana,Nishant Kumar
title CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis
title_short CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis
title_full CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis
title_fullStr CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis
title_full_unstemmed CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis
title_sort cocl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis
publisher Sociedad de Biología de Chile
publishDate 2019
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100210
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AT singhpriya cocl2simulatedhypoxiainducecellproliferationandaltertheexpressionpatternofhypoxiaassociatedgenesinvolvedinangiogenesisandapoptosis
AT kochbiplob cocl2simulatedhypoxiainducecellproliferationandaltertheexpressionpatternofhypoxiaassociatedgenesinvolvedinangiogenesisandapoptosis
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