2. Academic Validation
  3. Synergistic combination of isogarcinol isolated from edible fruits of Garcinia multiflora and dexamethasone to overcome leukemia glucocorticoid resistance

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

  • Biomed Pharmacother. 2023 Nov 30:170:115936. doi: 10.1016/j.biopha.2023.115936.
Qin Liu 1,  Zhen-Peng Niu 2,  Kun Yang 3,  Jing-Rui Song 4,  Xue-Nai Wei 4,  Yu-Bing Huang 4,  Chun-Mao Yuan 5,  Yan-Mei Li 6
Affiliations

Affiliations

  • 1 State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014 Guizhou, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 550025 Guizhou, China; Natural Products Research Center of Guizhou Province, Guiyang 550014, China.
  • 2 Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004 Guizhou, China.
  • 3 School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 550025 Guizhou, China.
  • 4 State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014 Guizhou, China; Natural Products Research Center of Guizhou Province, Guiyang 550014, China.
  • 5 State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014 Guizhou, China; Natural Products Research Center of Guizhou Province, Guiyang 550014, China. Electronic address: [email protected].
  • 6 State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014 Guizhou, China; Natural Products Research Center of Guizhou Province, Guiyang 550014, China. Electronic address: [email protected].
PMID: 38039755 DOI: 10.1016/j.biopha.2023.115936
Abstract

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.

Keywords

Apoptosis; C-Myc; Cell cycle; Dexamethasone resistance; Isogarcinol; Leukemia.

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