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Xanthohumol inhibits non-small cell lung cancer by activating PUMA-mediated apoptosis

Xiaozhi Li1, Longyu Jin1, Yuchao Ma1

  • 1Cardiothoracic Surgery, The Third XiangYa Hospital, Central South University, Changsha, Hunan 410013, China.

Toxicology
|March 8, 2022
PubMed

Insights

Xanthohumol, a compound from Hops, effectively combats non-small cell lung cancer (NSCLC) by inducing apoptosis through the PUMA pathway. This study reveals a novel mechanism for Xanthohumol

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Deregulation of apoptosis is crucial in cancer development.
  • Xanthohumol from Hops shows anti-tumor potential but its role in non-small cell lung cancer (NSCLC) is unclear.

Purpose of the Study:

  • To investigate the efficacy of Xanthohumol against NSCLC cells.
  • To elucidate the underlying molecular mechanisms of Xanthohumol's anti-cancer effects in NSCLC.

Main Methods:

  • In vitro studies using NSCLC cell lines (A549, H520, H358) and in vivo xenograft mouse models.
  • Analysis of cell viability, colony formation, apoptosis, and key protein expressions (PUMA, Akt, FOXO3a).

Main Results:

  • Xanthohumol inhibited NSCLC cell viability and colony formation, inducing apoptosis.
  • It activated mitochondrial apoptosis via upregulation of PUMA, involving Akt inhibition and FOXO3a dephosphorylation.
  • Silencing PUMA or FOXO3a reduced Xanthohumol-induced apoptosis.
  • In vivo, Xanthohumol suppressed tumor growth and increased PUMA expression in NSCLC xenografts.

Conclusions:

  • Xanthohumol demonstrates significant anti-tumor activity in NSCLC.
  • The anti-cancer effect is mediated through a novel PUMA-dependent pathway involving Akt and FOXO3a.
  • Xanthohumol represents a potential therapeutic agent for non-small cell lung cancer.
Keywords:
ApoptosisNon-small cell lung cancerPUMAXanthohumol

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