Albendazole inhibits HIF-1α-dependent glycolysis and VEGF expression in non-small cell lung cancer cells

Abstract

Albendazole (ABZ) has an anti-tumor ability and inhibits HIF-1α activity. HIF-1α is associated with glycolysis and vascular endothelial cell growth factor (VEGF) expression, which plays an important role in cancer progression. These clues indicate that ABZ exerts an anti-cancer effect by regulating glycolysis and VEGF expression. The aim of this study is to clarify the effects of ABZ on non-small cell lung cancer (NSCLC) cells and explore the underlying molecular mechanisms. The expression levels of HIF-1α and VEGF were detected using western blot analysis, and the effect of ABZ on glycolysis was evaluated by measuring the relative activities of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) and detecting the production of lactate in A549 and H1299 cells. The results showed that ABZ decreased the expression levels of HIF-1α and VEGF and suppressed glycolysis in under hypoxia, but not normoxic condition. Inhibiting HIF-1α also suppressed glycolysis and VEGF expression. Additionally, ABZ inhibited the volume and weight, decreased the relative activities of HK, PK, and LDH, and reduced the levels of HIF-1α and VEGF of A549 xenografts in mouse models. In conclusion, ABZ inhibited growth of NSCLC cells by suppressing HIF-1α-dependent glycolysis and VEGF expression.

Solid Polymeric Nanoparticles of Albendazole: Synthesis, Physico-Chemical Characterization and Biological Activity

“…In recent years, numerous in vitro and in vivo studies have provided results that support the applicability of the broad-spectrum anti-helminthic ABZ against various types of cancer [71][72][73][74][75].…”

The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs

“…Supplementary Table 1 ( 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 ) summarizes the antitumorigenicity of benzimidazole anthelmintics on cancer cell lines. Benzimidazole anthelmintics inhibit the progression of cancer through a variety of mechanisms.…”

The reverse Warburg effect is likely to be an Achilles' heel of cancer that can be exploited for cancer therapy

“…As a regulator of innate immune response, it also effects secretion of cytokines and metabolic pattern in CAFs [ 61 , 76 ]. HIF-1α induces hypoxia response, promotes transcription of angiogenic factors (such as VEGF) and mediates autophagy, mitophagy and aerobic glycolysis [ 77 , 78 ]. In the process of glycolysis, several glycolytic enzymes, such as 2 isoforms of pyruvate kinase M (PKM1 and PKM2), mono-carboxylate transporters (MCTs) and lactate dehydrogenase A and B (LDHA, LDHB) overexpress significantly [ 79 – 81 ].…”