Vitamin K(3) and K(5) are inhibitors of tumor pyruvate kinase M2

Cancer Lett. 2012 Mar 28;316(2):204-10. doi: 10.1016/j.canlet.2011.10.039. Epub 2011 Nov 4.

Abstract

Pyruvate kinase M2 (PKM2) is a rate-limiting enzyme of aerobic glycolysis in cancer cells and plays important roles in cancer metabolism and growth. Here we show that vitamin K(3) and K(5) (VK(3) and VK(5)) are relatively specific PKM2 inhibitors. VK(3) and VK(5) showed a significantly stronger potency to inhibit PKM2 than to inhibit PKM1 and PKL, 2 other isoforms of PK dominantly expressed in most adult tissues and liver. This study combined with previous reports supports that VK(3) and VK(5) have potential as adjuvant for cancer chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Glucose / metabolism
  • HeLa Cells
  • Humans
  • Lactic Acid / metabolism
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / metabolism
  • Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / pharmacology*
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / metabolism
  • Vitamin K 3 / analogs & derivatives*
  • Vitamin K 3 / pharmacology*

Substances

  • Antineoplastic Agents
  • Carrier Proteins
  • Membrane Proteins
  • Protein Kinase Inhibitors
  • Thyroid Hormones
  • Lactic Acid
  • Vitamin K 3
  • Glucose
  • vitamin k5