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New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways
Authors:Fatima Bouhtit  Mehdi Najar  Doua Moussa Agha  Rahma Melki  Mustapha Najimi  Khalid Sadki  Noureddine Boukhatem  Dominique Bron  Nathalie Meuleman  Abdellah Hamal  Laurence Lagneaux  Philippe Lewalle  Makram Merimi
Abstract:Acute myeloid leukemia (AML) is a cancer of the myeloid lineage of blood cells, and treatment for AML is lengthy and can be very expensive. Medicinal plants and their bioactive molecules are potential candidates for improving human health. In this work, we studied the effect of Ptychotis verticillata (PV) essential oil and its derivatives, carvacrol and thymol, in AML cell lines. We demonstrated that a combination of carvacrol and thymol induced tumor cell death with low toxicity on normal cells. Mechanistically, we highlighted that different molecular pathways, including apoptosis, oxidative, reticular stress, autophagy, and necrosis, are implicated in this potential synergistic effect. Using quantitative RT-PCR, Western blotting, and apoptosis inhibitors, we showed that cell death induced by the carvacrol and thymol combination is caspase-dependent in the HL60 cell line and caspase-independent in the other cell lines tested. Further investigations should focus on improving the manufacturing of these compounds and understanding their anti-tumoral mechanisms of action. These efforts will lead to an increase in the efficiency of the oncotherapy strategy regarding AML.
Keywords:AML-cancer therapy  drug combination-synergy  bioactive molecules  cell death  apoptotic and non-apoptotic pathways
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