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Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells

Cytotoxicity and apoptosis-inducing properties of compounds isolated from Garcinia subelliptica leaves were investigated. The hexane-soluble portion of MeOH extracts of G. subelliptica leaves that showed cytotoxic activity was separated to yield seven compounds 1–7. Chemical structure analysis using...

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Autores principales: Yun, YoungSook, Shioura, Mariko, Hitotsuyanagi, Yukio, Yotsumoto, Satoshi, Takahashi, Yuji, Aoyagi, Yutaka, Kinoshita, Takeshi, Takeya, Koichi, Inoue, Hideshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122622/
https://www.ncbi.nlm.nih.gov/pubmed/33919344
http://dx.doi.org/10.3390/molecules26092422
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author Yun, YoungSook
Shioura, Mariko
Hitotsuyanagi, Yukio
Yotsumoto, Satoshi
Takahashi, Yuji
Aoyagi, Yutaka
Kinoshita, Takeshi
Takeya, Koichi
Inoue, Hideshi
author_facet Yun, YoungSook
Shioura, Mariko
Hitotsuyanagi, Yukio
Yotsumoto, Satoshi
Takahashi, Yuji
Aoyagi, Yutaka
Kinoshita, Takeshi
Takeya, Koichi
Inoue, Hideshi
author_sort Yun, YoungSook
collection PubMed
description Cytotoxicity and apoptosis-inducing properties of compounds isolated from Garcinia subelliptica leaves were investigated. The hexane-soluble portion of MeOH extracts of G. subelliptica leaves that showed cytotoxic activity was separated to yield seven compounds 1–7. Chemical structure analysis using NMR spectroscopy and mass spectrometry confirmed that compound 1 was canophyllol, and compounds 2–7 were garcinielliptones N, O, J, G, F, and garcinielliptin oxide, respectively. Among them, garcinielliptone G (5) showed growth inhibition by causing apoptosis in THP-1 and Jurkat cells derived from human acute monocytic leukemia and T lymphocyte cells, respectively. Apoptosis induced by garcinielliptone G (5) was demonstrated by the detection of early apoptotic cells with fluorescein-labeled Annexin V and increases in cleaved caspase-3 and cleaved PARP protein levels. However, the addition of caspase inhibitor Z-VAD-FMK did not affect growth arrest or apoptosis induction. These results suggest that garcinielliptone G (5) can induce both caspase-3 activation and caspase-independent apoptosis. Therefore, garcinielliptone G (5) may be a potential candidate for acute leukemia treatment.
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spelling pubmed-81226222021-05-16 Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells Yun, YoungSook Shioura, Mariko Hitotsuyanagi, Yukio Yotsumoto, Satoshi Takahashi, Yuji Aoyagi, Yutaka Kinoshita, Takeshi Takeya, Koichi Inoue, Hideshi Molecules Article Cytotoxicity and apoptosis-inducing properties of compounds isolated from Garcinia subelliptica leaves were investigated. The hexane-soluble portion of MeOH extracts of G. subelliptica leaves that showed cytotoxic activity was separated to yield seven compounds 1–7. Chemical structure analysis using NMR spectroscopy and mass spectrometry confirmed that compound 1 was canophyllol, and compounds 2–7 were garcinielliptones N, O, J, G, F, and garcinielliptin oxide, respectively. Among them, garcinielliptone G (5) showed growth inhibition by causing apoptosis in THP-1 and Jurkat cells derived from human acute monocytic leukemia and T lymphocyte cells, respectively. Apoptosis induced by garcinielliptone G (5) was demonstrated by the detection of early apoptotic cells with fluorescein-labeled Annexin V and increases in cleaved caspase-3 and cleaved PARP protein levels. However, the addition of caspase inhibitor Z-VAD-FMK did not affect growth arrest or apoptosis induction. These results suggest that garcinielliptone G (5) can induce both caspase-3 activation and caspase-independent apoptosis. Therefore, garcinielliptone G (5) may be a potential candidate for acute leukemia treatment. MDPI 2021-04-21 /pmc/articles/PMC8122622/ /pubmed/33919344 http://dx.doi.org/10.3390/molecules26092422 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yun, YoungSook
Shioura, Mariko
Hitotsuyanagi, Yukio
Yotsumoto, Satoshi
Takahashi, Yuji
Aoyagi, Yutaka
Kinoshita, Takeshi
Takeya, Koichi
Inoue, Hideshi
Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells
title Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells
title_full Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells
title_fullStr Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells
title_full_unstemmed Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells
title_short Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells
title_sort garcinielliptone g from garcinia subelliptica induces apoptosis in acute leukemia cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122622/
https://www.ncbi.nlm.nih.gov/pubmed/33919344
http://dx.doi.org/10.3390/molecules26092422
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