Uncoupling Warburg effect and stemness in CD133+ve cancer stem cells from Saos-2 (osteosarcoma) cell line under hypoxia

Abstract

Cancer stem cells (CSCs) which are known to be residing deep inside the core of the tumor in its hypoxia niche is responsible for relapse of cancers. Owing to this hypoxic niche, the residing CSCs simultaneously fuel their stemness, cancerous and drug resistance properties. Attributes of CSCs are still not properly understood in its hypoxia niche. Addressing this, we sorted CSCs from Saos-2 (osteosarcoma) cell line using CD133 antibody. The CD133 CSCs exhibited quiescent cell proliferation in DNA doubling, Ca signaling and cell cycle analysis. CD133 CSCs exhibited increased production of ATP and lactate dehydrogenase (LDH) activity under hypoxia. CD133 cells exhibited decreased glucose uptake compared to ATP levels under hypoxia. Moreover, there was only negligible LDH activity in CD133 cells under normoxia which do not rely on Warburg effect. Stemness markers (such as c-Myc, SOX2, Oct4 and TERT), metastasis marker (CD44) and drug resistance marker (ABCG2) were highly expressed in CD133 cells. In summary, both CD133 cells of Saos-2 (osteosarcoma) cell line did not exhibit Warburg effect under normoxic condition. Moreover, this significantly indicates an uncoupling between stemness and Warburg effect in CD133. This work provides a novel insight into the metabolic and functional features of CSCs in a hypoxic environment which could open new avenues for therapeutic strategies aimed to target CSCs.

Biochemical and Cellular Characterization of New Radio-Resistant Cell Lines Reveals a Role of Natural Flavonoids to Bypass Senescence

“…The authors showed that this re-growth was associated with the presence of cancer stem cells (CSCs) in the lung tumor cell population [ 52 ]. In the present study, we did not investigate the presence of CSCs within the sub-populations of SAOS and HT29 cells selected after γ-ray irradiation, although their appearance and enrichment after drug treatments is a possible event, as reported by others [ 53 , 54 ]. For these reasons, we cannot exclude that “senescence associated-stemness” can be responsible for IR resistance in SAOS400 and HT500 cell lines.…”

Anticancer effects and lysosomal acidification in A549 cells by astaxanthin from Haematococcus lacustris

“…Effect of AXN (dose dependent) on cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide dye reduction was performed according to our pervious procedure [ 14 ]. Finally, the concentrations of AXN resulting in 50% reduction in cell viability at 24h (i.e., 50µM/ml) were then calculated and were used for further experiments.…”

Regulating glycolysis and heat shock proteins in Gannan yaks (<i>Bos</i> <i>grunniens</i>) in response to hypoxia of the Qinghai–Tibet Plateau

“…Previous studies have demonstrated that the phosphoinositide 3-kinase (PI3K)/Akt pathway becomes activated under hypoxic conditions, resulting in changes in the activities of various enzymatic biological pathways, including glucose metabolism (Xie et al, 2019). HIF1A has been demonstrated to be a glycolysis promoter that is regulated by PI3K/Akt pathway, and increased HIF1A expression induces the transcription of PDK4 (Kaelin and Ratcliffe, 2008;Lambert et al, 2010;Idelevich et al, 2011). PDK4 can phosphorylate the pyruvate dehydrogenase complex, inhibiting the oxidative decarboxylation of pyruvate into acetyl-CoA.…”