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

Merve Şansaçar; Özge Pekin; Emel Başak Gencer Akcok

Makale detayları

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

Yazarlar:

Merve Şansaçar | Özge Pekin | Emel Başak Gencer Akcok

Yayıncı:

Ondokuz Mayıs University

Ana Başlıklar:

Cancer Genetics | Cancer Cell Biology

Dergi:

Deneysel ve Klinik Tıp Dergisi Vol.41 Issue 3, pp.524-529

Belge Tipi:

Makale

Yayın Tarihi:

9/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001325913

pISSN:

1309-4483

Anahtar kelimeler:

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-VPI 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.

 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-VPI 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.

 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-VPI 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.

 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-VPI 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.

Makale detayları

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

Yazarlar:

Merve Şansaçar | Özge Pekin | Emel Başak Gencer Akcok

Yayıncı:

Ondokuz Mayıs University

Ana Başlıklar:

Cancer Genetics | Cancer Cell Biology

Dergi:

Deneysel ve Klinik Tıp Dergisi Vol.41 Issue 3, pp.524-529

Belge Tipi:

Makale

Yayın Tarihi:

9/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001325913

pISSN:

1309-4483

histone deacetylase inhibitors

cisplatin

acute myeloid leukemia

combination treatment

apoptosis

Sayı

Makale detayları

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

Yazarlar: Merve Şansaçar | Özge Pekin | Emel Başak Gencer Akcok

Yayıncı: Ondokuz Mayıs University

Ana Başlıklar: Cancer Genetics | Cancer Cell Biology

Dergi: Deneysel ve Klinik Tıp Dergisi Vol.41 Issue 3, pp.524-529

Belge Tipi: Makale

Yayın Tarihi: 9/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001325913

pISSN: 1309-4483

histone deacetylase inhibitors

cisplatin

acute myeloid leukemia

combination treatment

apoptosis

Sayı

Yazarlar:

Merve Şansaçar | Özge Pekin | Emel Başak Gencer Akcok

Yayıncı:

Ondokuz Mayıs University

Ana Başlıklar:

Cancer Genetics | Cancer Cell Biology

Dergi:

Deneysel ve Klinik Tıp Dergisi Vol.41 Issue 3, pp.524-529

Belge Tipi:

Makale

Yayın Tarihi:

9/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001325913

pISSN:

1309-4483