The Anticancer Effect of a Novel Quinoline Derivative 91b1 through Downregulation of Lumican

Abstract

Quinoline derivatives have been reported to possess a wide range of pharmaceutical activities. Our group previously synthesized a series of quinoline compounds, in which compound 91b1 showed a significant anticancer effect. The purpose of this study was to evaluate the anticancer activity of compound 91b1 in vitro and in vivo, and screen out its regulated target. A series of cancer cell lines and nontumor cell lines were treated with compound 91b1 by MTS cytotoxicity assay and cell-cycle assay. In vivo anticancer activity was evaluated by a xenografted model on nude mice. Target prediction of 91b1 was assessed by microarray assay and confirmed by pancancer analysis. Relative expression of the target gene Lumican was measured by qRT-PCR. 91b1 significantly reduced tumor size in the nude mice xenograft model. Lumican was downregulated after 91b1 treatment. Lumican was proven to increase tumorigenesis in vivo, as well as cancer cell migration, invasion, and proliferation in vitro. The results of this study suggest that the anticancer activity of compound 91b1 probably works through downregulating the gene Lumican.

Synthesis and biological evaluation of novel 2-morpholino-4-anilinoquinoline derivatives as antitumor agents against HepG2 cell line

“…35,36 Lumican is overexpressed in a variety of cancers, and it is thought to be responsible for promoting cancer cell migration, invasion, and proliferation, while its downregulation is important in reducing cancer cell migration and invasion. 37,38 The novel quinoline derivative (compound 91b1) developed by Yuan Zhou demonstrated antitumor efficacy in nude mice via downregulation of lumican. In addition, Toshiyuki Ishiwata's group found that lumican plays a vital function in the prevention of human embryonic kidney 293 cell attachment, 39 as well as resulting in morphological changes to cell shape and appearance, and hence altering cell adhesion ability.…”

“…This was achieved by downregulating lumican, a small leucinerich proteoglycan linked to several cancer types, which is linked to pro-tumorigenic or antitumorigenic activity. 19 Another group concluded that IND-2, a quinoline derivative, can decrease the proliferation of prostate cancer cells, and so could be utilized to control their growth, proliferation, and metastasis. 20 Due to the broad range of biological and pharmacological properties of quinoline and its derivatives, they are considered an important class of compounds for new drug development.…”

The Landscape of Small Leucine-Rich Proteoglycan Impact on Cancer Pathogenesis with a Focus on Biglycan and Lumican

“…A novel quinoline compound 91b1, which has strong anticancer effects in different cancer cell line models and in vivo, downregulates lumican mRNA levels, which are overexpressed in many cancers. Zhou et al correlate lumican downregulation with suppressed cell proliferation and modulated cell cycle progression [142].…”

“…In addition to increased vascular permeability, vasodilatation, and the recruitment of inflammatory cells, VEGF triggers the inhibition of apoptosis and increases cellular proliferation. The production of angiogenic signaling molecules leads to tumor vascularization, which is an essential step in tumor progression [142]. ECM activity is crucial to the distinct phases of the inflammation-associated angiogenic response [159].…”

“…As far as lumican is concerned, a study suggested that its ability to inhibit Snail activity, which is a significant trigger of epithelial-to-mesenchymal transition, may be used as a base for anticancer therapy [184]. Furthermore, a recent study showed that a quinoline derivative, i.e., compound 91b1, mediates its significant anticancer effects by downregulating the lumican gene [142].…”