Abstract：
Abnormal tryptophan metabolism is linked to cancer and neurodegenerative diseases, and tryptophan metabolites have been reported as potential prostate cancer (PCa) biomarkers. However, little is known about the bioactivities of tryptophan metabolites on PCa cell growth. In this study, MTT and transwell assays were used to study the cytotoxicities of 13 major tryptophan metabolites on PCa and normal prostate epithelial cell lines. Ultraperformance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was used to analyze metabolic changes in cells treated with tryptamine. Flow cytometry, confocal imaging, and Western blot were used to test the apoptosis induced by tryptamine. It was shown that tryptamine had obvious inhibitory effects on PCa cell lines PC-3 and LNCaP, stronger than those on the normal prostate cell line RWPE-1. Tryptamine was further shown to induce apoptosis and inhibit PC-3 cell migration. Metabolic changes including amino acid metabolism related to cell proliferation and metastasis were found in PC-3 cells treated with tryptamine. Furthermore, a PC-3 xenograft mouse model was used to study the effect of tryptamine in vivo. The intratumoral injection of tryptamine was demonstrated to significantly reduce the tumor growth and tumor sizes in vivo; however, intraperitoneal treatment resulted in increased tumor growth. Such dual effects in vivo advanced our understanding of the bioactivity of tryptamine in regulating prostate tumor development, in addition to its major role as a neuromodulator.
摘要：
色氨酸代谢异常与癌症和神经退行性疾病有关，和色氨酸代谢物已被报道为潜在的前列腺癌（PCa）生物标志物。然而,色氨酸代谢物对PCa细胞生长的生物活性知之甚少。在这项研究中,MTT和transwell测定法用于研究13种主要色氨酸代谢物对PCa和正常前列腺上皮细胞系的细胞毒性。超高效液相色谱-高分辨率质谱（UPLC-HRMS）用于分析用色胺处理的细胞中的代谢变化。流式细胞术,共焦成像，Westernblot检测色胺诱导的细胞凋亡。结果表明，色胺对PCa细胞系PC-3和LNCaP有明显的抑制作用，强于正常前列腺细胞系RWPE-1。进一步显示色胺诱导细胞凋亡并抑制PC-3细胞迁移。在用色胺处理的PC-3细胞中发现了代谢变化，包括与细胞增殖和转移相关的氨基酸代谢。此外，使用PC-3异种移植小鼠模型来研究体内色胺的作用。肿瘤内注射色胺被证明可以显著减少体内肿瘤的生长和肿瘤的大小；然而，腹膜内治疗导致肿瘤生长增加。这种体内的双重作用促进了我们对色胺在调节前列腺肿瘤发展中的生物活性的理解，除了作为神经调质的主要作用。
