Vitamin K(3) and K(5) are inhibitors of tumor pyruvate kinase M2.
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.
Plasma kininogen levels in the peripheral venous blood of untreated patients with active rheumatoid disease was found to be more than twice the levels measured in healthy normal individuals or in convalescing uncomplicated fracture patients. Treatment with oral indomethacin or aspirin lowered the kininogen levels nearly to normal. Sequential studies showed that the fall in kininogen was very rapid, occurring within 1-2 hours of ingestion of drug, and was parallelled by reduction in the clinical indices of inflammation. Control studies showed that the kininogen changes were not due to changes in plasma volume or non-specific changes in plasma protein concentration. Indomethacin treatment had no effect on plasma kininogen levels in healthy volunteers. The significance of this finding will be discussed.