A combination of salinomycin or its C20 triphenylphosphonium-conjugated derivative with carboplatin leads to autophagy in ovarian cancer cells - An in vitro study

  • Eur J Med Chem. 2026 Apr 5:307:118656. doi: 10.1016/j.ejmech.2026.118656.
Marcin Michalak  1 ,  Michał S Lach  2 ,  Katarzyna Regulska  3 ,  Marta Jędrzejczyk  4 ,  Michał Antoszczak  4 ,  Monika A Rosochowicz-Kamińska  5 ,  Błażej Nowakowski  1 ,  Wiktoria M Suchorska  6 ,  Adam Huczyński  7
Affiliations
  • 1. Surgical, Oncological and Endoscopic Gynaecology Department, Greater Poland Cancer Center, Garbary 15, Poznań, 61-866, Poland.
  • 2. Radiobiology Laboratory, Greater Poland Cancer Center, Garbary 15, Poznań, 61-866, Poland.
  • 3. Department of Pharmacy, Greater Poland Cancer Center, Garbary 15, Poznań, 61-866, Poland.
  • 4. Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, Poznań, 61‒614, Poland.
  • 5. Radiobiology Laboratory, Greater Poland Cancer Center, Garbary 15, Poznań, 61-866, Poland; Department of Orthopedics and Traumatology, Poznań University of Medical Sciences, 28 Czerwca 1956 Roku 135/147 Street, Poznań, 61-545, Poland.
  • 6. Radiobiology Laboratory, Greater Poland Cancer Center, Garbary 15, Poznań, 61-866, Poland; Department of Electroradiology, Poznań University of Medical Sciences, Garbary 15, Poznań, 61-866, Poland.
  • 7. Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, Poznań, 61‒614, Poland. Electronic address: [email protected].
PMID: 41691997 DOI: 10.1016/j.ejmech.2026.118656
Abstract

Ovarian Cancer (OvCa) remains a major therapeutic challenge due to limited treatment options and frequent late-stage diagnosis, which contribute to high recurrence rates and mortality. Advances in synthetic organic chemistry and the development of novel oncology-targeted molecules offer promising new directions. In this study, we aimed to evaluate salinomycin (SAL) and its semisynthetic derivatives as potential candidates for OvCa therapy. Among the synthesized C20 SAL derivatives, we selected compound 8, featuring a triphenylphosphonium (TPP+) motif and exhibiting a cytotoxicity profile comparable to that of the parent molecule, for further investigation of its Anticancer mechanism of action. In combination with carboplatin (CBP), we investigated the interactions and effects on cell viability, cell cycle distribution, Reactive Oxygen Species (ROS) production, mitochondrial membrane potential, and Autophagy markers. Our findings indicated that SAL and 8 share a similar mechanism of action, inducing G0/G1 cell cycle arrest, reducing ROS production, and disrupting mitochondrial integrity, thereby promoting Autophagy rather than classical cell death pathways in the tested OvCa cell lines. These results suggest that the TPP+-conjugated SAL derivatives may be promising therapeutic candidates for the management of OvCa, either as monotherapy or in combination with CBP and related drugs.

Keywords
Autophagy; Mitochondrial damage; Ovarian cancer; Platinum drugs; Salinomycin; TPP(+) conjugation.
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