Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study

Abstract

Metabolomics is a comprehensive assessment of endogenous metabolites of a biological system in a holistic context. In this study, we evaluated the in vivo anti-melanoma activity of aqueous extract of Forsythiae Fructus (FAE) and globally explored the serum metabolome characteristics of B16-F10 melanoma-bearing mice. UPLC/Q-TOF MS combined with pattern recognition approaches were employed to examine the comprehensive metabolic signatures and differentiating metabolites. The results demonstrated that FAE exhibited remarkable antitumor activity against B16-F10 melanoma in C57BL/6 mice and restored the disturbed metabolic profile by tumor insult. We identified 17 metabolites which were correlated with the antitumor effect of FAE. Most of these metabolites are involved in glycerophospholipid metabolisms. Notably, several lysophosphatidylcholines (LysoPCs) significantly decreased in tumor model group, while FAE treatment restored the changes of these phospholipids to about normal condition. Moreover, we found that lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX) were highly expressed in melanoma, and FAE markedly down-regulated their expression. These findings indicated that modulation of glycerophospholipid metabolisms may play a pivotal role in the growth of melanoma and the antitumor activity of FAE. Besides, our results suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma and other malignant tumors.

One extraction tool for in vitro-in vivo extrapolation? SPME-based metabolomics of in vitro 2D, 3D, and in vivo mouse melanoma models

“…A database search revealed a total of 256 previously reported compounds related to the B16F10 cell line [ [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] ]. In four of these studies, LC-MS was used for instrumental analysis [ [22] , [23] , [24] , [25] ] while NMR was employed in nine cases [ [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] ]. In vivo metabolomics was considered in eight cases [ 22 , [29] , [30] , [31] , [32] , [33] , [34] , [35] ].…”

“…In four of these studies, LC-MS was used for instrumental analysis [ [22] , [23] , [24] , [25] ] while NMR was employed in nine cases [ [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] ]. In vivo metabolomics was considered in eight cases [ 22 , [29] , [30] , [31] , [32] , [33] , [34] , [35] ]. Among them, only one study was performed with the use of MS as an analytical platform and B16 as a cancer model, with serum chosen as a matrix [ 22 ].…”

Peucedanum ostruthium Inhibits E-Selectin and VCAM-1 Expression in Endothelial Cells through Interference with NF-κB Signaling

“…Anti-inflammatory [59,61,62], anti-tumour [59,63], antioxidant [64] and anti-viral activities [15,58,60].…”

Chinese Medicines for Cancer Treatment from the Metabolomics Perspective

“…of Oleaceae family, shows potential anticancer properties. To characterize in detail the action mechanism, Bao et al conducted a UPLC/Q-TOF MS-based metabolomics of serum from B16-F10 melanoma-bearing mice model in vivo [65]. Aqueous extract of FAE was found to restore the disturbed metabolic profile by increasing several LysoPCs in glycerophospholipid metabolisms, revealing that the regulation of glycerophospholipid metabolisms may have an essential role in the antineoplastic property of FAE.…”