Metabolic characteristics of prostate cancer cells with high metastatic potential revealed by (S)-ethyl 1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate inhibition

Baoyan Ding; Wei Meng; Xiaoling Zang; Zhihua Lv

doi:10.1016/j.jpba.2024.116611

Metabolic characteristics of prostate cancer cells with high metastatic potential revealed by (S)-ethyl 1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate inhibition

J Pharm Biomed Anal. 2024 Dec 1:255:116611. doi: 10.1016/j.jpba.2024.116611. Online ahead of print.

Authors

Baoyan Ding¹, Wei Meng¹, Xiaoling Zang², Zhihua Lv³

Affiliations

¹ School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong 266003, PR China.
² School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong 266003, PR China; Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao, Shandong 266237, PR China. Electronic address: zangxiaoling@ouc.edu.cn.
³ School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong 266003, PR China; Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao, Shandong 266237, PR China.

PMID: 39662125
DOI: 10.1016/j.jpba.2024.116611

Abstract

A small molecule, (S)-ethyl 1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate (SEC), has been reported to be capable of suppressing metastasis of prostate cancer (PCa) cells. In this study, SEC was used to study the metabolic responses of PCa cell lines (LNCaP, PC3, and DU145) with different metastatic potential and the alterations of mTOR, p-mTOR, AMPK, and p-AMPK levels, when the PCa cells were inhibited. The ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based analysis showed that SEC induced the decreases of intracellular metabolites including glutamic acid, glutamine, and histidine (LNCaP); creatinine, citric acid/isocitric acid, and aspartic acid (PC3); and spermidine, S-hydroxymethylglutathione, LPE (20:3), and palmitic amide (DU145), and the increases of intracellular LPC (18:0) (LNCaP); tyrosine, pyroglutamic acid/pyrroline hydroxycarboxylic acid (PC3); and tyrosine, phenylalanine, phenylacetylglycine, spermine, histidine, and choline (DU145). SEC also caused the decrease of extracellular N1-acetylspermidine (LNCaP), erythronic acid/threonic acid (PC3 and DU145), and nicotinic acid/picolinic acid (DU145), and the increase of extracellular 5'-methylthioadenosine (DU145). High metastatic PC3 and DU145 cells exhibited changes in aromatic amino acid metabolism including tyrosine metabolism, phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism (PC3 and DU145), TCA cycle (PC3), arginine and proline metabolism, and glycerophospholipid metabolism (DU145), different from the low metastatic LNCaP cells, which had changes in alanine, aspartate, and glutamate metabolism, and arginine biosynthesis. In addition, the levels of p-mTOR and p-AMPK were shown to be obviously downregulated and upregulated, respectively, in high metastatic PC3 and DU145 cells upon SEC inhibition, while this behavior was not detected in LNCaP cells.

Keywords: High metastatic PCa cells; Metabolic changes; P-AMPK level; P-mTOR level; SEC.