TY - JOUR
T1 - Extracellular O2 level and pH modulation affected the human breast cancer stem cells’ survival and stemness
AU - Yustisia, Ika
AU - Jusman, Sri Widia
AU - Wanandi, Septelia Inawati
N1 - Funding Information:
Acknowledgments: We are grateful to Resda Akhra (RA), Purnamawati Huang (PH), and Gladies M Neolaka (GN) for their contribution to perform experiments (RA), and their assistance for the statistical analysis and data management (GN, PH). The work was supported by the Grant of International Indexed Publication for Final Assignment of the Postgraduate Student from Universitas Indonesia Year 2016 (Hibah Publikasi Internasional Terindeks Untuk Tugas Akhir Mahasiswa UI Tahun 2016).
Publisher Copyright:
© 2017 American Scientific Publishers All rights reserved.
PY - 2017/7
Y1 - 2017/7
N2 - Introduction: It has been reported that cancer stem cells could maintain their viability and stemness under certain extracellular changes. Therefore, efforts that modulate tumor hypoxia and acidity should be compelled in order to impede the growth of cancer stem cells. This study was aimed to analyze the effect of extracellular pH and O2 level modulation on viability, apoptosis, and stemness of the human CD24−/CD44+ breast cancer stem cells (BCSCs). Methods: The primary BCSCs (CD24−/CD44+ cells) were cultured under hypoxia (1% O2) or under supplementation of sodium bicarbonate (100 mM) for various periods. After each incubation time, cell viability was determined by trypan blue exclusion assay and apoptosis was examined using flow cytometry with Annexin V/PI assay. Furthermore, total RNA was isolated for qRT-PCR analysis of HIF1, ALDH1 and Klf4 mRNA expression. Results: This study demonstrated that hypoxia could suppress BCSC proliferation, but inhibit the cell apoptosis. Alkaline pH could also suppress BCSC proliferation and promote early apoptosis at the same time. Interestingly, the expressions of ALDH1 and KLF4 were downregulated in hypoxia-treated BCSCs which might be regulated through the increase of HIF1. Conversely, ALDH1 and Klf4 expressions were upregulated in sodium bicarbonate-treated BCSCs under alkaline pH. Conclusion: The modulation of extracellular pH and the O2 level has diverse effects on the viability, apoptosis, dan stemness of BCSCs. Therefore, we suggest that targeting tumor hypoxia and acidity may be a prospective therapeutic strategy to eradicate BCSCs.
AB - Introduction: It has been reported that cancer stem cells could maintain their viability and stemness under certain extracellular changes. Therefore, efforts that modulate tumor hypoxia and acidity should be compelled in order to impede the growth of cancer stem cells. This study was aimed to analyze the effect of extracellular pH and O2 level modulation on viability, apoptosis, and stemness of the human CD24−/CD44+ breast cancer stem cells (BCSCs). Methods: The primary BCSCs (CD24−/CD44+ cells) were cultured under hypoxia (1% O2) or under supplementation of sodium bicarbonate (100 mM) for various periods. After each incubation time, cell viability was determined by trypan blue exclusion assay and apoptosis was examined using flow cytometry with Annexin V/PI assay. Furthermore, total RNA was isolated for qRT-PCR analysis of HIF1, ALDH1 and Klf4 mRNA expression. Results: This study demonstrated that hypoxia could suppress BCSC proliferation, but inhibit the cell apoptosis. Alkaline pH could also suppress BCSC proliferation and promote early apoptosis at the same time. Interestingly, the expressions of ALDH1 and KLF4 were downregulated in hypoxia-treated BCSCs which might be regulated through the increase of HIF1. Conversely, ALDH1 and Klf4 expressions were upregulated in sodium bicarbonate-treated BCSCs under alkaline pH. Conclusion: The modulation of extracellular pH and the O2 level has diverse effects on the viability, apoptosis, dan stemness of BCSCs. Therefore, we suggest that targeting tumor hypoxia and acidity may be a prospective therapeutic strategy to eradicate BCSCs.
KW - Breast cancer stem cells
KW - Cell viability
KW - Extracellular pH
KW - Stemness
KW - Tumor hypoxia
UR - http://www.scopus.com/inward/record.url?scp=85030235690&partnerID=8YFLogxK
U2 - 10.1166/asl.2017.9372
DO - 10.1166/asl.2017.9372
M3 - Article
AN - SCOPUS:85030235690
VL - 23
SP - 6685
EP - 6689
JO - Advanced Science Letters
JF - Advanced Science Letters
SN - 1936-6612
IS - 7
ER -