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Review Open Access

Resurrection biology: Melatonin as a modulator of anastasis (Review)

  • Authors:
    • Alexandros Georgiou
    • Russel J. Reiter
    • Vassilis Zoumpourlis
    • Demetrios A. Spandidos
  • View Affiliations / Copyright

    Affiliations: School of Medicine, University of Crete, 71003 Heraklion, Greece, Department of Cellular and Structural Biology, UT Health, San Antonio, TX 78229, USA, Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece, Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece
    Copyright: © Georgiou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 293
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    Published online on: September 2, 2026
       https://doi.org/10.3892/mmr.2026.14004
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Abstract

Although apoptosis is regarded as an irreversible and terminal process, recent research has identified anastasis as a cellular mechanism that enables cell recovery even after the activation of executioner caspases. While important in supporting tissue homeostasis following mild or transient injury, anastasis presents significant challenges in oncology, as cancer cells may exploit this phenomenon to evade chemotherapy, subsequently acquiring aggressive traits such as genomic instability, stem‑like properties, and increased metastatic capacity. N‑acetyl‑5‑methoxytryptamine (melatonin), recognized for its antioxidant activity and role as a mitochondrial regulator, has been associated with several biological processes that overlap with pathways involved in anastasis, including mitochondrial bioenergetics, redox homeostasis, and DNA repair mechanisms. However, direct evidence supporting a role for melatonin in regulating anastasis remains limited. The present review consolidated current insights into the molecular regulation of anastasis, examining its biphasic transcriptional profile and oncogenic consequences, while exploring the mechanistic links between melatonin biology and pathways relevant to apoptotic recovery and evaluating the therapeutic prospects of melatonin in targeting anastasis as a strategy to mitigate tumor recurrence and improve clinical outcomes.
View Figures

Figure 1

Schematic overview of the principal
oncogenic outcomes associated with anastasis. (A) Although
apoptotic stimuli ordinarily induce cellular death, (B) the process
of anastasis enables cells to reverse this trajectory. This
recovery promotes a form of genetic reprogramming and mutagenesis,
which may contribute to the emergence of aggressive cancer cell
phenotypes exhibiting increased chemoresistance, increased motility
and invasiveness and stem cell-like properties. Created in
BioRender. Georgiou, A. (2026) https://BioRender.com/eppw4go

Figure 2

The pleiotropic actions of melatonin
associated with cellular anastasis. Melatonin accumulates within
mitochondria, serving as a direct free radical scavenger while
maintaining their structural and functional integrity through
mechanisms such as radical avoidance and mitochondrial membrane
stabilization (top left). In non-malignant cells, melatonin
supports DNA integrity by stimulating antioxidative enzymes,
regulating DNA repair processes, and upregulating proteins
responsible for maintaining DNA stability (top right). Conversely,
in cancer cells, melatonin exerts context-dependent effects that
inhibit DNA repair. For example, by suppressing TRIP13 expression,
melatonin reduces the activity of repair proteins RAD51 and XRCC5,
thus enhancing cellular sensitivity to cytotoxic therapies (bottom
left). Additionally, melatonin promotes the formation of TNTs,
which facilitate the intercellular transport of membrane vesicles,
small molecules, and functional mitochondria, contributing to the
restoration of bioenergetics and supporting anastasis (bottom
right). Created in BioRender. Georgiou, A. (2026) https://BioRender.com/0f7njf4. ROS, reactive
oxygen species; TRIP13, thyroid hormone receptor interactor 13;
RAD51, DNA repair protein RAD51 homolog 1; XRCC5, DNA repair
protein Ku80; TNTs, tunneling nanotubes.
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Copy and paste a formatted citation
Spandidos Publications style
Georgiou A, Reiter RJ, Zoumpourlis V and Spandidos DA: Resurrection biology: Melatonin as a modulator of anastasis (Review). Mol Med Rep 34: 293, 2026.
APA
Georgiou, A., Reiter, R.J., Zoumpourlis, V., & Spandidos, D.A. (2026). Resurrection biology: Melatonin as a modulator of anastasis (Review). Molecular Medicine Reports, 34, 293. https://doi.org/10.3892/mmr.2026.14004
MLA
Georgiou, A., Reiter, R. J., Zoumpourlis, V., Spandidos, D. A."Resurrection biology: Melatonin as a modulator of anastasis (Review)". Molecular Medicine Reports 34.4 (2026): 293.
Chicago
Georgiou, A., Reiter, R. J., Zoumpourlis, V., Spandidos, D. A."Resurrection biology: Melatonin as a modulator of anastasis (Review)". Molecular Medicine Reports 34, no. 4 (2026): 293. https://doi.org/10.3892/mmr.2026.14004
Copy and paste a formatted citation
x
Spandidos Publications style
Georgiou A, Reiter RJ, Zoumpourlis V and Spandidos DA: Resurrection biology: Melatonin as a modulator of anastasis (Review). Mol Med Rep 34: 293, 2026.
APA
Georgiou, A., Reiter, R.J., Zoumpourlis, V., & Spandidos, D.A. (2026). Resurrection biology: Melatonin as a modulator of anastasis (Review). Molecular Medicine Reports, 34, 293. https://doi.org/10.3892/mmr.2026.14004
MLA
Georgiou, A., Reiter, R. J., Zoumpourlis, V., Spandidos, D. A."Resurrection biology: Melatonin as a modulator of anastasis (Review)". Molecular Medicine Reports 34.4 (2026): 293.
Chicago
Georgiou, A., Reiter, R. J., Zoumpourlis, V., Spandidos, D. A."Resurrection biology: Melatonin as a modulator of anastasis (Review)". Molecular Medicine Reports 34, no. 4 (2026): 293. https://doi.org/10.3892/mmr.2026.14004
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