Xanthatin, a natural product isolated and purified from the fruits of Xanthium sibiricum with cytotoxic, antibacterial and antifungal activities, can inhibit murine melanoma B16-F10 cell proliferation possibly associated with activation of Wnt/β-catenin pathway and its activity against melanoma tumor might also be relevant to inhibition of angiogenesis.
Xanthatin is isolated from Xanthium strumarium leaves. Xanthatin exhibits strong antitumor activities against a variety of cancer cells through apoptosis persuasion and shows anti-inflammatory activities by inhibiting PGE2 synthesis and 5-lipoxygenase activity. Xanthatin is against T. b. brucei with an IC50 value of 2.63 µg/mL and exhibits weak irreversible inhibition of parasite specific trypanothione reductase[3]. Xanthatin is a potent and orally active inhibitor of VEGFR2 kinase activity with an IC50 of 3.8 μM and prominently blocks the phosphorylation of VEGFR2 at Tyr951 site. Xanthatin (0-40 μM; 24 hours) has obscure inhibition effect on the proliferation of HUVEC in the absence of VEGF. Xanthatin (5-40 μM; 24 hours) inhibits breast cancer cell proliferation in a dose responsive manner. Xanthatin inhibits HCC1937, MDA-MB-415, SK-BR-3, MCF-7 and MDA-MB-231 with IC50 values of 81 μM, 31 μM, 38 μM, 30 μM, and 17 μM, respectively. Xanthatin (0-10 μM; 24 hours) dose dependently suppresses the phosphorylation of STAT3 (Ser727), at the same time, it also results in a rapid dephosphorylation of down-stream kinases of STAT3, including PI3K and Akt, including PI3K (p-PI3K p85 tyr458) and Akt[4]. Xanthatin significantly inhibited the migration and invasion of human HT-29 and HCT-116 colon cancer cells. Concomitantly, xanthatin promoted complex II activity and oxidative phosphorylation (OXPHOS), resulting in mitochondrial damage and cell death in HT-29 cells. Furthermore, xanthatin inhibited the phosphorylation of mTOR, the phosphorylation of 4E-binding protein 1 (4E-BP1) and c-myc in HT-29 cells[5].
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