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<p>Despite the significant anti-proliferative effects of telomerase inhibition on acute myeloid leukemia (AML) cells, complementary therapies that promote apoptosis on AML cells have been suggested. This investigation assessed the impact of concurrently targeting telomerase with BIBR1532 and mitochondrial function with Tigecycline on inducing apoptosis in AML cell models. KG-1a and KG-1 AML cells were treated with IC50 concentrations of the telomerase inhibitor BIBR1532 and the mitochondrial inhibitor Tigecycline, both alone and in combination, for 48&#xa0;h. Cell viability were assessed by MTT assay and Combination Index. Apoptosis was analyzed by Annexin V/7AAD staining using flow cytometry. Gene expression (Bax, Bad, Bcl-2, Bcl-xl, hTERT) was evaluated by quantitative real-time PCR (qRT-PCR), and Bax/Bcl-2 protein levels were measured by ELISA. Telomere length was determined by real-time PCR. Our result showed that, Co-inhibition of telomerase and mitochondria with IC50 values of BIBR1532 and Tigecycline for 48&#xa0;h synergistically reduced the proliferation rate of AML (KG-1a and KG-1) cells. Besides, telomerase and mitochondria inhibition (TI/MI) synergistically augmented induction of apoptosis coupled with the up-regulation of Bax, Bad genes and down-regulation of Bcl-2, Bcl-xl and hTERT on AML cells. Also, TI/MI significantly changed Bax and Bcl-2 protein levels and reduced telomere length. In conclusion, the combined use of TI/MI induced anti-proliferative effects and induction of apoptosis by down-regulation of anti-apoptotic and up-regulation of pro-apoptotic genes and proteins levels and shortening of telomere length on AML cells.</p>

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Combined Inhibition of telomerase and mitochondria synergistically promote apoptosis in AML cell lines

  • 期刊论文

  • 发表日期：

    2025年11月18日

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  • Hossein Kalarestaghi,
  • Khadijeh Dizaji Asl,
  • Zeinab Mazloumi,
  • Mohsen Hemmati-Dinarvand,
  • Abbas Ghotaslou,
  • Majid Nejati,
  • Ali Rafat

摘要

Despite the significant anti-proliferative effects of telomerase inhibition on acute myeloid leukemia (AML) cells, complementary therapies that promote apoptosis on AML cells have been suggested. This investigation assessed the impact of concurrently targeting telomerase with BIBR1532 and mitochondrial function with Tigecycline on inducing apoptosis in AML cell models. KG-1a and KG-1 AML cells were treated with IC50 concentrations of the telomerase inhibitor BIBR1532 and the mitochondrial inhibitor Tigecycline, both alone and in combination, for 48 h. Cell viability were assessed by MTT assay and Combination Index. Apoptosis was analyzed by Annexin V/7AAD staining using flow cytometry. Gene expression (Bax, Bad, Bcl-2, Bcl-xl, hTERT) was evaluated by quantitative real-time PCR (qRT-PCR), and Bax/Bcl-2 protein levels were measured by ELISA. Telomere length was determined by real-time PCR. Our result showed that, Co-inhibition of telomerase and mitochondria with IC50 values of BIBR1532 and Tigecycline for 48 h synergistically reduced the proliferation rate of AML (KG-1a and KG-1) cells. Besides, telomerase and mitochondria inhibition (TI/MI) synergistically augmented induction of apoptosis coupled with the up-regulation of Bax, Bad genes and down-regulation of Bcl-2, Bcl-xl and hTERT on AML cells. Also, TI/MI significantly changed Bax and Bcl-2 protein levels and reduced telomere length. In conclusion, the combined use of TI/MI induced anti-proliferative effects and induction of apoptosis by down-regulation of anti-apoptotic and up-regulation of pro-apoptotic genes and proteins levels and shortening of telomere length on AML cells.