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Epigenetic modifiers either individually or in specific combinations impair viability of patient-derived glioblastoma cell line while exhibit moderate effect on normal stem cells growth

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Abstract

Glioblastomas (GBM), also known as glioblastoma multiforme, are the most aggressive type of brain cancer. Currently, there is no effective treatment for GBM, highlighting the pressing need for new therapeutic strategies. In a recent study, we demonstrated that specific combinations of epigenetic modifiers significantly affect the metabolism and proliferation rate of the two most aggressive GBM cell lines, D54 and U-87. Importantly, these combinations exhibited minimal effects on the growth of normal stem cells. In this study, we extended our investigation to include a patient-derived GBM stem cell line. Our results showed that the combinations of modulators of histone and DNA covalent modifying enzymes that synergistically suppress D54 and U87 cell line growth also impair the viability of the patient-derived GBM stem cell line. These findings suggest that epigenetic modifiers alone or in specific combinations exhibit a cytotoxic effect on established and low-passage patient-derived GBM cell lines, and thus could be a promising therapeutic approach for this type of brain cancer.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by Cell Reprogramming & Therapeutics LLC and partially by the support of National Institute of Health (NIH) grant 1 R43 CA221490.

Funding

This work was supported by Cell Reprogramming & Therapeutics LLC and partially by the support of National Institute of Health (NIH) grant 1 R43 CA221490

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Authors and Affiliations

  1. Cell Reprogramming & Therapeutics LLC, Wauwatosa (Milwaukee County), Wauwatosa, WI, 53226, USA

    Arshak R. Alexanian & Heidi Marie Stoellinger

  2. Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA

    Virginea de Araujo Farias & Alfredo Quiñones-Hinojosa

Authors
  1. Arshak R. Alexanian
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  2. Heidi Marie Stoellinger
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  3. Virginea de Araujo Farias
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  4. Alfredo Quiñones-Hinojosa
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Contributions

Dr Alexanian contributed to study motivation, experimental design and writing the paper; Heidi Stoellinger contribution – technical support; Virginea De Araujo Farias and Alfredo Quinones-Hinojosa contribution – generation of patient derived cell line and with technical support for cells growth and expansion. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Arshak R. Alexanian.

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The authors have no relevant financial or non-financial interests to disclose.

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No human or animal subjects involved. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of cell Reprogramming & Therapeutics LLC and Mayo Clinic.

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Alexanian, A.R., Stoellinger, H.M., de Araujo Farias, V. et al. Epigenetic modifiers either individually or in specific combinations impair viability of patient-derived glioblastoma cell line while exhibit moderate effect on normal stem cells growth. Invest New Drugs 41, 371–375 (2023). https://doi.org/10.1007/s10637-023-01370-7

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  • DOI: https://doi.org/10.1007/s10637-023-01370-7

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