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.
Highlights
Cancer has been a leading cause of death worldwide, both in developed and developing countries[1]
We previously reported that Forsythiae Fructus aqueous extract (FAE) exhibited potent antitumor activity in vitro and in vivo[17]
FAE (10 g/kg) treatment group had a 47.2 ± 14.4% inhibitory rate on tumor growth in mice comparing tumor weight with the control group (Fig. 1B). These results demonstrated that FAE exhibited a significant antitumor activity against B16-F10 melanoma in vivo
Summary
Cancer has been a leading cause of death worldwide, both in developed and developing countries[1]. We found that the regulation of glycerophospholipid metabolism may perform an important role in the tumor growth of melanoma and antitumor effects of FAE, and the serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma and efficacy evaluation of antitumor treatment.
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