Investigation of the in vitro effects of mitochondrial-derived peptide (MOTS-c) on imatinib-resistant chronic myeloid leukemia model


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Yalçın P., Kızıldağ S., Ateş H., Yüce Z., Baykal Köse S.

The Injector, cilt.2, sa.3, ss.108, 2023 (Hakemli Dergi)

  • Yayın Türü: Makale / Özet
  • Cilt numarası: 2 Sayı: 3
  • Basım Tarihi: 2023
  • Dergi Adı: The Injector
  • Sayfa Sayıları: ss.108
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Objective: The mitochondrial short open reading frame (MOTS-c) of 12S rRNA type-c is one of the 16 amino acid MDPs encoded by the mitochondrial genome. There are studies of this biopeptides role in metabolic responses and cellular stress. However, MOTS-c's role on leukemia and drug resistance are unknown. Our aim is to investigate the possible contribution of exogenic MOTS-c exposure to cell viability and cell death in chronic myeloid leukemia (CML) and imatinib resistant-CML in vitro.Methods: The ancestral K562 and K562-derived imatinib resistant cell line (K562-IR) is used for the leukemia model. Both cell lines was exposed to different doses and durations of MOTS-c (0.1, 1.0, and 10 μM) exogenously. We were evaluated MOTS-c function on these cell lines in terms of cell viability (MTT), cell death (Annexin-PI), and lipid peroxidation. Statistical analysis of the data was performed using IBM SPSS Statistics 24.0 with one-way ANOVA.Results: MOTS-c significantly triggered cell death in both cell lines. Apoptosis in resistant cells was significant within the first 24 h at a concentration of 10 μM (p<0.039), and K562-IR induced significantly apoptosis at 72 h- 10 μM compared to ancestor cells (p<0.046). While the viability rate decreased in ancestral cells depending on the MOTS-c concentration, responses in the resistant group were found to be variable. However, in terms of lipid peroxidation, no significant difference was found between ancestral and resistant cell lines.Conclusion: Cancer metabolism is a primary target for overcoming drug resistance, which develops over time despite the discovery of smart molecules. Our results are important as they show for the first time the effect of MOTS-c on viability and cell death in secondary drug resistance in cancer. Additionally, our results suggest that the cytotoxic effect of MOTS-c may vary depending on the concentration. More research is needed to understand MOTS-c and its functions.Keywords: Chronic myeloid leukemia, drug resistance, imatinib, mitochondrial derived peptides, MOTS-c.108