Caudatin blocks the proliferation, stemness and glycolysis of non-small cell lung cancer cells through the Raf/MEK/ERK pathway

CONTEXT: The antitumor effects of caudatin have been explored in multiple cancers, but the research on lung cancer has not been fully understood. OBJECTIVE: We explored the effects of caudatin on non-small cell lung cancer (NSCLC) in vitro and in vivo. MATERIALS AND METHODS: In the in vitro experiments, 0, 25, 50 and 100 μM of caudatin were selected to examine the effects on stemness and glycolysis. Subcutaneous tumour xenografts were constructed by injecting the nude mice (BALB/C) with 5 × 10(6) H1299 cells. In the in vivo experiments, all nude mice were divided into the caudatin group (50 mg/kg/day, n = 5) and the sham group (equal amount of DMSO, n = 5). RESULTS: The IC(50) of caudatin for H1299 and H520 cells was 44.68 μM and 69.37 μM, respectively. Compared with caudatin 0 μM group, cell apoptosis rate was increased about 10 times and cell stemness was decreased by 75–85% in caudatin 100 μM group. Glucose uptake (65–80% reduction), lactic acid production (75–80% reduction), ATP level (70–80% reduction) and the expression of HK2 and LDHA (75–85% reduction) were decreased in caudatin 100 μM group. The expression of Raf/MEK/ERK pathway related proteins was decreased to 20–25% by caudatin. Tumour weight (about 70% reduction) and the expression of stemness, glycolysis and Raf/MEK/ERK pathway related proteins (about 50–75% reduction) were suppressed by caudatin in vivo. DISCUSSION AND CONCLUSIONS: We revealed that caudatin blocked stemness and glycolysis in NSCLC for the first time. More experiments about exact dosage of caudatin in vivo should be conducted.