Emerson Ferreira Queiroz

LC-MS/MS ANALYSIS OF SUGARCANE EXTRACTS AND DIFFERENTIATION OF MONOSACCHARIDES MOIETIES OF FLAVONE C-GLYCOSIDES

LC-MS/MS data of the flavones from extracts of nonmodified and transgenic sugarcane (“Bowman-Birk” and “Kunitz”) led to the proposition of characteristic fragmentations that can be applied to identify the monosaccharides glucose, arabinose, and rhamnose in C-glycosylflavones. Collision-induced dissociation (CID) MS/MS generated diagnostic ions for different linked sugars in C-glycosylflavone–O-glycoside and C-glycosylflavone–O-acid derivatives, and the combination of MS data with postcolumn derivatization using UV shift reagents (which provide complementary information to determine the substitution patterns in the flavone skeleton) allowed for the identification of seven flavones not previously reported in sugarcane: 6-methoxyluteolin-8-C-arabinosyl-7-O-glucoside; diosmetin-8-C-arabinosyl-7-O-arabinoside; vitexin-7-O-rhamnoside; diosmetin-8-C-rhamnosyl-7-O-glucoside; tricetin-8–C-(6‴-O-sinapoylglucoside); 7,4′ di-O-methylapigenin-8-C-arabinosyl-rhamnoside; and luteolin-8-C-rhamnosyl-7-O-rhamnoside.

Tannins from Syzygium guineense suppress Wnt signaling and proliferation of Wnt-dependent tumors through a direct effect on secreted Wnts.

Triple-negative breast cancer (TNBC) and colon cancer (CC) are two stigmatic examples of poorly treatable tumors, whose progression critically depends upon hyperactivation of the Wnt signaling. Development of specific anti-Wnt inhibitors is required to develop drugs against these and other Wnt-dependent cancers. Natural products, especially plants, have been used for the treatment of various diseases from ancient times. We examined extracts from several indigenous Cameroonian herbs and tested their effects on proliferation and Wnt signaling in TNBC and CC cells. Extracts from fruit rouge, Syzygium guineense Wall. (Myrtaceae), demonstrated a strong activity against these cancer cells, as well as CC organoids. We found TNBC cells to significantly upregulate expression of Wnt3a, and the effects of S. guineense extracts on TNBC cell proliferation correlated with inhibition of the Wnt3a-induced β-catenin stabilization and transcriptional response. HPLC analysis revealed that the active components belong to tannins. We found a direct destabilizing effect of S. guineense extract on Wnt3a and other Wnt proteins, identifying a novel mechanism of action of tannins on the Wnt signaling pathway and cancer cell proliferation. Being edible, this African plant may have an important cancer-preventive nutritional value.