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Hydroxycitric Acid Inhibits Chronic Myelogenous Leukemia Growth through Activation of AMPK and mTOR Pathway

Doriana Verrelli1, Luca Dallera1, Massimo Stendardo1

  • 1IRCCS European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.

Nutrients
|July 9, 2022
PubMed

Insights

Hydroxycitric acid (HCA), a natural compound, activates AMP-activated protein kinase (AMPK) to inhibit chronic myelogenous leukemia (CML) cell growth. This nutraceutical approach shows promise for CML treatment by affecting key cellular pathways.

Area of Science:

  • Oncology
  • Biochemistry
  • Pharmacology

Background:

  • AMP-activated protein kinase (AMPK) activation is a key strategy for targeting cancer cell growth, particularly in leukemias.
  • Naturally occurring compounds are being investigated for their potential to stimulate AMPK activity as a therapeutic approach.

Purpose of the Study:

  • To investigate the potential of hydroxycitric acid (HCA), a natural compound from Garcinia gummi-gutta, as an AMPK activator for treating chronic myelogenous leukemia (CML).
  • To elucidate the mechanisms underlying HCA's anti-leukemic effects in K562 cells.

Main Methods:

  • In vitro and in vivo xenograft models using the K562 CML cell line.
  • Analysis of AMPK and ATP citrate lyase (ACLY) interaction.
  • Assessment of mTOR pathway activation and unfolded protein response (UPR) via the eIF2α/ATF4 pathway.

Main Results:

  • HCA demonstrated potent AMPK activity and inhibited K562 cell growth in vitro and in vivo.
  • A direct, HCA-sensitive interaction between AMPK and ACLY was identified.
  • HCA treatment led to co-activation of AMPK and mTOR, alongside enhanced UPR and G2/M cell cycle arrest.

Conclusions:

  • Hydroxycitric acid (HCA) exhibits significant anti-leukemic effects against CML by activating AMPK and influencing key cellular pathways.
  • HCA's mechanism involves direct interaction with ACLY, mTOR co-activation, and induction of UPR, leading to cell cycle arrest and DNA fragmentation.
  • HCA represents a promising nutraceutical strategy for CML treatment.
Keywords:
AMPKCMLhydroxycitric acidnutraceuticals

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