Suppression of PMA-induced human fibrosarcoma HT-1080 invasion and metastasis by kahweol via inhibiting Akt/JNK1/2/p38 MAPK signal pathway and NF-κB dependent transcriptional activities. (March 2019)

• Record Type: Journal Article
• Authors: Choi, Jae Ho; Hwang, Yong Pil; Jin, Sun Woo; Lee, Gi Ho; Kim, Hyung Gyun; Han, Eun Hee; Kim, Sang Kyum; Kang, Keon Wook; Chung, Young Chul; Jeong, Hye Gwang
• Is Part Of: Food and chemical toxicology. Volume 125(2019)
• Page Start: 1
• Page End: 9
• Publication Date: 2019-03
• Subjects: Kahweol -- Metastasis -- MMP-9 -- NF-κB -- AP-1 -- Chemotherapeutic agent; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.12.038
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Coffee is one of the widely sales beverage worldwide and contains numerous phytochemicals that are beneficial to health. Kahweol acetate (KA), a coffee-specific diterpene, exhibits anti-tumoric properties in human tumoric cells. However, the effect of KA on the metastasis and invasion of cancer cells and the underlying mechanisms remain unclear. The objectives of this study were to estimate the anti-tumor activity of KA and reveal the possible molecular mechanisms. KA markedly inhibited the cell proliferation enhanced by phorbol 12-myristate 13-acetate (PMA) in human fibrosarcoma cells. As well as, KA attenuated PMA-induced cell migration and invasion in a concentration-dependent manner. KA suppressed PMA-enhanced activation of matrix metalloproteinase-9 (MMP-9) through suppression of nuclear factor kappa B (NF-κB) activation. KA repressed the PMA-induced phosphorylation of Akt, c-Jun N-terminal kinase (JNK) 1/2, and p38 MAPK, which are signaling molecules upstream of MMP-9 expression. In summary, we demonstrated that the anti-tumor effects of KA might occur through the inhibition of Akt/JNK1/2/p38 MAPK phosphorylation and downregulation of NF-κB activation, leading to a decrease in MMP-9 expression. Thus, KA is a useful chemotherapeutic agent that may contribute to prevent to the metastatic tumor. Graphical abstract: Image 1 Highlights: Kahweol acetate (KA) may ameliorate metastatic tumor. KA attenuated PMA-induced cell migration and invasion. KA suppressed PMA-increased MMP-9 expression. KA inhibited PMA-enhanced NF-κB activation. KA inhibited PMA-induced Akt/JNK1/2/p38 MAPK phosphorylation.