Garmultin-A Incites Apoptosis in CB3 Cells Through miR-17-5p by Attenuating Poly (ADP-Ribose) Polymerase-1.

Autor: Qiu J; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China.; Department of Immunology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, P.R. China., Chen L; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Yang J; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Varier KM; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Gajendran B; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Yao Y; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Liu W; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Song J; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Rao Q; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Long Q; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Yuan C; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Hao X; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China., Li Y; State Key Laboratory for Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, P.R. China.; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, P.R. China.
Jazyk: angličtina
Zdroj: Dose-response : a publication of International Hormesis Society [Dose Response] 2022 Oct 11; Vol. 20 (4), pp. 15593258221130681. Date of Electronic Publication: 2022 Oct 11 (Print Publication: 2022).
DOI: 10.1177/15593258221130681
Abstrakt: Background: Leukemia accounts for a large number of deaths, worldwide, every year. Treating this ailment is always a challenging job. Recently, oncogenic miRNA leading to apoptosis are highly promising targets of many natural products. In this study, Garmultin-A (GA), isolated from the bark of Garcinia multiflora , was elucidated for its anti-leukemic effect in CB3 cells.
Methods: The effect of the compound on CB3 cell viability was detected by MTT assay and apoptosis by FITC Annexin V/PI and Hochest 33258 staining. The western blot analysis assessed the BAX, BCL2, cMYC, pERK, and PARP-1 protein levels. Autodock analysis predicted the ligand-protein interactions. q-RT-PCR quantified the miR-17-5p expression. Luciferase assay confirmed the interaction between PARP-1 and miR-17-5p.
Results: We uncover that GA leads to apoptosis by inducing overexpression of miR-17-5p and significantly downregulate PARP-1 protein levels in CB3 cells. The overexpression of miR-17-5p promotes apoptosis, and the miR-17-5p antagomirs restore GA-triggered apoptosis. Notably, we disclose that PARP-1 is a direct target of miR-17-5p. Increased pro-apoptotic and reduced anti-apoptosis protein levels were also observed in GA-treated CB3 cells.
Conclusion: These results provide critical insights that GA could induce apoptosis in CB3 cells through targeting miR-17-5p by attenuating PARP-1. Thus, GA could act as a novel therapeutic agent for erythroleukemia.
Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
(© The Author(s) 2022.)
Databáze: MEDLINE
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