2. Academic Validation
  3. Epigenetic Activity of Cancer Therapy Drugs Revealed by HeLa TI Cell-Based Assay

Epigenetic Activity of Cancer Therapy Drugs Revealed by HeLa TI Cell-Based Assay

  • Epigenomes. 2026 Feb 23;10(1):14. doi: 10.3390/epigenomes10010014.
Varvara Maksimova 1,  Valeriia Popova 1,  Alyona Kholodova 1 2,  Julia Makus 1,  Olga Usalka 1 3,  Eugenia Lylova 1,  Aleksandr Kudriashov 4,  Gennady Belitsky 1,  Marianna Yakubovskaya 1,  Kirill Kirsanov 1 5
Affiliations

Affiliations

  • 1 Department of Carcinogenesis Mechanisms, National Medical Research Center of Oncology Named After N.N. Blokhin, Ministry of Health of Russia, Moscow 115478, Russia.
  • 2 Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological Agency, Moscow 119121, Russia.
  • 3 Department of Biology, Tufts University, Medford, MA 02144-2401, USA.
  • 4 Institute of Biomedicine, Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow 117997, Russia.
  • 5 Institute of Medicine, The Patrice Lumumba Peoples' Friendship University of Russia, Moscow 117198, Russia.
PMID: 41892363 DOI: 10.3390/epigenomes10010014
Abstract

Background/objectives: The aberrant epigenetic landscape of Cancer cells has attracted wide attention, motivating the search for new epigenetically active drugs both for Anticancer therapy and for overcoming the drug resistance promoted by epigenetic changes. The use of epi-drugs in Cancer therapy requires consideration of the influence of applied treatment on epigenetic regulation of gene expression. Therefore, it is reasonable to screen epigenetically active compounds among the drugs widely used in clinical oncology.

Methods: We applied the HeLa TI cell-based assay to analyze the epigenetic activity of 40 drugs including 22 chemotherapeutic, 2 immunotherapeutic, 13 targeted, and 3 palliative agents. Reactivation of the epigenetically silenced GFP reporter gene integrated into the genome of HeLa TI cells was assessed using flow cytometry.

Results: Statistically significant increases in the proportions of GFP-positive cells were demonstrated for the alkylating agent chlorambucil; the antimetabolites cytarabine, fluorouracil, gemcitabine, and pemetrexed; the platinum-based compounds cisplatin, and oxaliplatin; the Topoisomerase Inhibitor topotecan; and the antimicrotubule agents docetaxel, vincristine, and eribulin. Epigenetic activity was also detected for the targeted-therapy agents AZD8055, wortmannin, and cetuximab, as well as for the corticosteroid dexamethasone. Thus, epigenetic activity was revealed for 15 drugs widely used in Cancer therapy, which possess different modes of action.

Conclusions: Our findings show that many Anticancer therapy agents modulate the epigenetic landscape of Cancer cells, providing a rationale for expanding their therapeutic applications and enhancing the efficacy of combination strategies by overcoming epigenetically driven chemoresistance.

Keywords

HeLa TI; anticancer therapy; drugs; epigenetic activity; screening.

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