Ginsenoside compound K attenuates metastatic growth of hepatocellular carcinoma, which is associated with the translocation of nuclear factor-κB p65 and reduction of matrix metalloproteinase-2/9.
The intestinal metabolite of ginseng saponin, compound K (CK), has various chemopreventive and chemotherapeutic activities, including anti-tumor activity. However, the functional mechanisms through which CK attenuates metastatic growth in hepatocellular carcinoma (HCC) remain unclear. Here, using multiple IN VITRO and IN VIVO models, we reported that CK strongly attenuated colony formation, adhesion, and invasion of HCC cells IN VITRO and dramatically inhibited spontaneous HCC metastatic growth IN VIVO. At the molecular level, immunofluorescence and Western blotting analysis confirmed that inhibition of metastatic growth of HCC induced by CK treatment caused a time-dependent decrease in nuclear NF- κB p65 and a concomitant increase in cytosolic NF- κB p65, indicating that CK suppressed the activation of the NF- κB pathway. Meanwhile, our study showed that the inhibition of matrix metalloproteinase2/9 (MMP2/9) expression caused by CK treatment was associated with NF- κB p65 nuclear export. Taken together, our results not only revealed that NF- κB p65 nuclear export and the reduction of MMP2/9 expression were associated with the metastatic inhibition induced by CK, but also suggested that CK may become a potential cytotoxic drug in the prevention and treatment of HCC.
Ming
Yanlin
Y
Research and Development Center for Plant Medicine and Plant Drugs, Xiamen Overseas Chinese Subtropical , Plant Introduction Garden, Xiamen, PR China.
Chen
Zhongyan
Z
Chen
Lianghua
L
Lin
Dejian
D
Tong
Qingxuan
Q
Zheng
Zhizhong
Z
Song
Gang
G
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000502:physiology*; D009362:Neoplasm Metastasis; D005894:Panax / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D036145:Ginsenosides; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases; D016328:NF-kappa B; D010936:Plant Extracts; C112772:ginsenoside compound K