Synergistic combination of isogarcinol isolated from edible fruits of Garcinia multiflora and dexamethasone to overcome leukemia glucocorticoid resistance

Isogarcinol (ISO), a cytotoxic polycyclic polyprenylated acylphloroglucinol isolated from the edible fruits of Garcinia multiflora. However, synergistic combination of ISO and dexamethasone (DEX) to overcome leukemia glucocorticoid resistance has never been investigated. Therefore, in this study, th...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2024-01, Vol.170, p.115936-115936, Article 115936
Main Authors: Liu, Qin, Niu, Zhen-Peng, Yang, Kun, Song, Jing-Rui, Wei, Xue-Nai, Huang, Yu-Bing, Yuan, Chun-Mao, Li, Yan-Mei
Format: Article
Language:English
Subjects:
Apoptosis
C-Myc
Cell cycle
Dexamethasone resistance
Isogarcinol
Leukemia
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Summary:Isogarcinol (ISO), a cytotoxic polycyclic polyprenylated acylphloroglucinol isolated from the edible fruits of Garcinia multiflora. However, synergistic combination of ISO and dexamethasone (DEX) to overcome leukemia glucocorticoid resistance has never been investigated. Therefore, in this study, the effects of ISO in combination with DEX was conducted on leukemia in vivo and glucocorticoid resistance in vitro. As a result, the combination of the two compounds could efficiently inhibit leukemia progression in mice and reverse DEX resistance in acute lymphoblastic leukemia (ALL) Jurkat cells. Significantly, our findings indicated that c-Myc may be a potential target of ISO, as it is involved in cell cycle arrest and apoptosis by the combination of ISO and DEX in Jurkat cells. Furthermore, western blot analysis revealed that ISO and DEX inhibits the PI3K/Akt/mTOR signaling pathway and promotes the nuclear translocation of glucocorticoid receptor (GR), which activates target genes NR3C1 and TSC22D3, leading to apoptosis in Jurkat cells. Hence, our results suggest that ISO, as a safe and effective food-derived agent, can enhance the anti-leukemia effects of DEX. [Display omitted] •Isogarcinol and dexamethasone inhibit the progression of leukemia in mice and repress the growing of leukemia cells.•Isogarcinol may be target c-Myc to enhance the sensitivity of Jurker cells to dexamethasone.•Isogarcinol combined with DEX can promote the translocation of GR to the nucleus.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2023.115936