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

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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+ve CSCs exhibited quiescent cell proliferation in DNA doubling, Ca2+ signaling and cell cycle analysis. CD133+ve CSCs exhibited increased production of ATP and lactate dehydrogenase (LDH) activity under hypoxia. CD133+ve cells exhibited decreased glucose uptake compared to ATP levels under hypoxia. Moreover, there was only negligible LDH activity in CD133+ve 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+ve cells. In summary, both CD133+ve/−ve 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+ve. 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.

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Acknowledgements

This work was supported in the name of research fellowship to first author from CTDT (Centre for Technology development and Transfer)—Anna university, Chennai, Tamil Nadu, India. We acknowledge the financial support from MHRDCEMA F.NO-5-3/2015-TS VII and BUILDER program BT/PR12153/INF/22/200/2014 to AD.

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Authors and Affiliations

  1. Centre for Biotechnology, Anna University, Chennai, Tamil Nadu, 600025, India

    Pavani Koka, Reddy Sailaja Mundre, Rohini Rangarajan, Yamini Chandramohan, Raghunandha Kumar Subramanian & Anuradha Dhanasekaran

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  1. Pavani Koka
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  2. Reddy Sailaja Mundre
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  3. Rohini Rangarajan
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  4. Yamini Chandramohan
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  5. Raghunandha Kumar Subramanian
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  6. Anuradha Dhanasekaran
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Correspondence to Anuradha Dhanasekaran.

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Koka, P., Mundre, R.S., Rangarajan, R. et al. Uncoupling Warburg effect and stemness in CD133+ve cancer stem cells from Saos-2 (osteosarcoma) cell line under hypoxia. Mol Biol Rep 45, 1653–1662 (2018). https://doi.org/10.1007/s11033-018-4309-2

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  • DOI: https://doi.org/10.1007/s11033-018-4309-2

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