Leelamine suppresses cMyc expression in prostate cancer cells in vitro and inhibits prostate carcinogenesis in vivo

Abstract

Aim: Leelamine (LLM) inhibits the growth of human prostate cancer cells but the underlying mechanism is not fully understood. The present study was undertaken to determine the effect of LLM on cMyc, which is overexpressed in a subset of human prostate cancers. Methods:The effect of LLM on cMyc expression and activity was determined by western blotting/confocal microscopy and luciferase reporter assay, respectively. A transgenic mouse model of prostate cancer (Hi-Myc) was used to determine the chemopreventive efficacy of LLM.Results: Exposure of androgen-sensitive (LNCaP) and castration-resistant (22Rv1) human prostate cancer cells to LLM resulted in downregulation of protein and mRNA levels of cMyc. Overexpression of cMyc partially attenuated LLM-mediated inhibition of colony formation, cell viability, and cell migration in 22Rv1 and/or PC-3 cells. LLM treatment decreased protein levels of cMyc targets (e.g., lactate dehydrogenase), however, overexpression of cMyc did not attenuate these effects. A trend for a decrease in the expression level of cMyc protein was discernible in 22Rv1 xenografts from LLM-treated mice compared with control mice. LLM treatment (10 mg/kg body weight, 5 times/week) was well-tolerated by Hi-Myc transgenic mice. The incidence of high-grade prostatic intraepithelial neoplasia, adenocarcinoma in situ, and microinvasion were lower in LLM-treated Hi-Myc mice but the difference was not statistically significant.

Potential Application of Leelamine as a Novel Regulator of Chemokine-Induced Epithelial-to-Mesenchymal Transition in Breast Cancer Cells

“…In this study, our goal was to investigate the diverse molecular mechanisms through which LEE could target the invasion and migration of breast cancer cells. We selected LEE as it has been previously reported to exhibit anticancer efficacy in some studies but its impact on the CXCR7/4 axis and EMT process has not been reported [ 3 , 4 , 5 , 6 , 7 , 8 ]. Thus, our study mainly examined the impact of LEE on the regulation of the EMT process by targeting the CXCR7/4 signaling axis in breast cancer cells.…”

“…In prostate cancer cells, LEE caused inhibition of fatty acid synthesis mediated by sterol regulatory element-binding protein 1 (SREBP1) [ 7 ]. In another study, it was reported that the anticancer effects of LEE in the prostate cancer were mediated through downregulation of cMyc in vitro and in vivo [ 8 ]. In the present study, the anticancer activity of LEE in human breast cancer cells was explored.…”

Inflammation induced by lipopolysaccharide advanced androgen receptor expression and epithelial-mesenchymal transition progress in prostatitis and prostate cancer

“…Compared with former study (16), LNCap cells and primary prostate epithelial cells were be used in this study to investigate NF-κB regulates AR expression and EMT in prostatitis and PCa. Compared with DU145 cells and PC3 cells, LNCap cells showed more androgen-sensitive and have remarkable epithelial properties, which widely used in EMT research (17). What's more, this is the first time to apply primary prostate epithelial cells, which sampled from patients who were suspected of PCa and had histological prostatitis (HP) confirmed by pathological biopsy, in prostatitis-PCa-EMT research.…”