Reprogramming induced by isoliquiritigenin diminishes melanoma cachexia through mTORC2-AKT-GSK3β signaling

Xiao Yu Chen, Defang LI, Ji Chun Han, Bo Wang, Zheng Ping Dong, Li Na Yu, Zhao Hai Pan, Chuan Jun Qu, Ying Chen, Shi Guo Sun, Qiu Sheng Zheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Isoliquiritigenin (ISL), a member of the flavonoids, is known to have antitumor activity in vitro and in vivo. The effect of ISL on reprogramming in cancer cells, however, remains elusive. In this study, we investigated the effect of ISL on reprogramming in human melanoma A375 cells. ISL (15 μg/ml) significantly inhibited A375 cell proliferation, anchorage independent cell proliferation and G2/M cell cycle arrest after ISL exposure for 24 h. However, there were no significant changes in apoptosis rate. Terminal differentiation indicators (melanin content, melanogenesis mRNA expression, tyrosinase (TYR) activity) were all up-regulated by ISL treatment. In ISL-treated cells, glucose uptake, lactate levels and mRNA expression levels of GLUT1 and HK2 were significantly decreased, and accompanied by an increase in O2 consumption rate (OCR) and adenosine triphosphate (ATP) deficiency. Protein expression levels of mTORC2-AKT-GSK3β signaling pathway components (mTOR, p-mTOR, RICTOR, p-AKT, p-GSK3β) decreased significantly after ISL treatment. Cotreatment of ISL and the mTOR-specific inhibitor Ku-0063794 had a synergistic effect on the inhibition of proliferation, and increased melanin content and TYR activity. Glucose uptake and lactate levels decreased more significantly than treatment with ISL alone. These findings indicate that ISL induced reprogramming in A375 melanoma cells by activating mTORC2-AKT-GSK3β signaling.

Original languageEnglish
Pages (from-to)34565-34575
Number of pages11
JournalOncotarget
Volume8
Issue number21
DOIs
Publication statusPublished - 2017

Scopus Subject Areas

  • Oncology

User-Defined Keywords

  • Cachexia
  • Isoliquiritigenin
  • Melanoma
  • MTORC2-AKT-GSK3β signaling
  • Reprogramming

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