Targeting HDAC enzymes by SAHA enhances the cytotoxic effects of cisplatin on acute myeloid leukemia cells


Şansaçar M., Pekin Ö., Gencer Akçok E. B.

Journal of Experimental and Clinical Medicine (Turkey), cilt.41, sa.3, ss.524-529, 2024 (Scopus) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 41 Sayı: 3
  • Basım Tarihi: 2024
  • Doi Numarası: 10.52142/omujecm.41.3.14
  • Dergi Adı: Journal of Experimental and Clinical Medicine (Turkey)
  • Derginin Tarandığı İndeksler: Scopus, Academic Search Premier
  • Sayfa Sayıları: ss.524-529
  • Anahtar Kelimeler: acute myeloid leukemia, apoptosis, cisplatin, combination treatment, histone deacetylase inhibitors
  • Abdullah Gül Üniversitesi Adresli: Evet

Özet

Chemotherapy is a widely used therapeutic approach to combat hematopoietic malignancies such as acute myeloid leukemia (AML). Although cisplatin is known as the first-generation platinum-based chemotherapy inhibitor, the wide use of cisplatin eventually leads to drug resistance, which is the biggest impediment to cancer chemotherapy. Histone deacetylase enzyme (HDAC) inhibitors have the ability to induce cell cycle arrest and apoptosis in different types of cancer, which stands as a promising alternative for those cancer patients not appropriate for intensive chemotherapy. This study concluded that there was a significant decrease in the proliferation of MOLM-13 and MV4-11 FLT3-ITD+ AML cell lines with the increasing SAHA and cisplatin concentrations in 48 hours using MTT cell proliferation assay. Moreover, the combination of SAHA and cisplatin led to a reduction in the proliferation of both cell lines correlated with the synergistic effect of the two drugs depending on the combination index (CI). Furthermore, investigating apoptosis for combined administration resulted in increased induction of apoptosis by Annexin-V/PI double staining. In conclusion, although additional studies are needed to fully elucidate the molecular mechanism underlying this combination, we propose a new approach to targeting AML, as AML increases over time with drug resistance and the consequent year-on-year increase in patient mortality.