Xanthoxylin (Brevifolin), isolated from Zanthoxylum piperitum (Japanese pepper tree) and Sapium sebiferum (Chinese tallowtree), is a cytotoxic and fungicidal compound with the characteristics of a typical phytoalexin.
Xanthoxylin (RCX) exhibits potent cytotoxicity in a panel of different cancer cells. It presents IC50 values of 1.6 and 26.0?μM for the HCT116 and ACP-03 cancer cell lines, respectively. Xanthoxylin causes apoptosis in a time- and concentration-dependent manner and induces mitochondrial depolarization in HepG2 cells. It induces DNA intercalation, inhibited DNA synthesis and triggered the caspase-mediated apoptosis pathway in HepG2 cells, as observed by cell shrinkage, internucleosomal DNA fragmentation, externalization of phosphatidylserine, loss of mitochondrial transmembrane potential and activation of caspase-3, -8 and -9[1]. Xanthoxylin increases melanin production, number of dendrites, tyrosinase, and microphthalmia-associated transcription factor (MITF) expression in cultured B16F10 cells[2].
Xanthoxylin presents a potent in vivo antitumor effect in C.B-17 SCID mice engrafted with HepG2 cells[1].
[1] Nanashara C. de Carvalho, et al. Cell Death & Diseasevolume. 2018, 9: 79. [2] Wanmai Moleephan, et al. Asian Biomedicine. 2012, 6(3): 413-422.