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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Xiaomin Chen, Fengqi Liu, Dade Rong, Limei Xu, Xiuzhen Tong* and Haihe Wang*

DOI: 10.2174/1871520622666211228110630

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Decitabine Enhances Acute Myeloid Leukemia Cell Apoptosis through SH3BGRL Upregulation

Page: [2274 - 2281] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: SH3-domain-binding glutamic acid-rich protein-like protein (SH3BGRL) is downregulated in acute myeloid leukemia (AML). Clinically, DNA demethylating drug decitabine (DAC) combined with traditional chemotherapies reveals better efficacy on AML patients than the conventional chemotherapies alone. Our previous results revealed that human SH3-domain-binding glutamic acid-rich protein-like protein (SH3BGRL) plays a tumor suppressive role in AML but whether there is a connection between DAC and SH3BGRL expression remains elusive.

Methods: Here, we tentatively treated AML cell lines U937, MV4, and HL-60 with DAC and Western Blots, RT-PCR was used to detect the expression of SH3BGRL. Cell proliferation and apoptosis were determined using Annexin V/7- AAD staining. Real-time RT-PCR and Western blot were used to determine the expression of SH3BGRL mRNA and protein. Methylation-specific PCR was used to quantify the DNA methylation in AML cell lines.

Results: DAC had cytotoxicity in HL-60, MV4, and U937. In U937 cell lines, treatment with DAC showed the upregulation of cleaved caspase3, PARP, and SH3BGRL. Upon treatment, up-regulation of SH3BGRL mRNA and protein was dose-dependent and this activity was partially inhibited in endogenous SH3BGRL knockdown cell lines.

Conclusion: Thus, our results demonstrated a possibly cytotoxic role of DAC on AML cells by upregulation of SH3BGRL expression at epigenetic modulation level and the methylation status in the SH3BGRL promoter region could be a supplemental diagnostic marker to the precise administration of DAC to AML patients.

Keywords: Acute myeloid leukemia, SH3BGRL, apoptosis, decitabine, methylation, DAC.

Graphical Abstract

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