Inhibitory Activity of (+)-Usnic Acid against Non-Small Cell Lung Cancer Cell Motility

Abstract

Lichens are symbiotic organisms that produce various unique chemicals that can be used for pharmaceutical purposes. With the aim of screening new anti-cancer agents that inhibit cancer cell motility, we tested the inhibitory activity of seven lichen species collected from the Romanian Carpathian Mountains against migration and invasion of human lung cancer cells and further investigated the molecular mechanisms underlying their anti-metastatic activity. Among them, Alectoria samentosa, Flavocetraria nivalis, Alectoria ochroleuca, and Usnea florida showed significant inhibitory activity against motility of human lung cancer cells. HPLC results showed that usnic acid is the main compound in these lichens, and (+)-usnic acid showed similar inhibitory activity that crude extract have. Mechanistically, β-catenin-mediated TOPFLASH activity and KITENIN-mediated AP-1 activity were decreased by (+)-usnic acid treatment in a dose-dependent manner. The quantitative real-time PCR data showed that (+)-usnic acid decreased the mRNA level of CD44, Cyclin D1 and c-myc, which are the downstream target genes of both β-catenin/LEF and c-jun/AP-1. Also, Rac1 and RhoA activities were decreased by treatment with (+)-usnic acid. Interestingly, higher inhibitory activity for cell invasion was observed when cells were treated with (+)-usnic acid and cetuximab. These results implied that (+)-usnic acid might have potential activity in inhibition of cancer cell metastasis, and (+)-usnic acid could be used for anti-cancer therapy with a distinct mechanisms of action.

In vitro cytotoxic and antiproliferative effects of usnic acid on hormone‐dependent breast and prostate cancer cells

“…UA prominently caused to apoptotic death in many cancer cells . We also found that UA induced apoptosis in LNCaP and MCF7 cells.…”

“…The most interesting is UA produced by Usnea species . UA has been reported in many studies that to be an antiproliferative agent, apoptosis inducer, and a cell cycle arrestor in different cancer cells, such as MCF7, HeLa, HCT‐116, A2780, HT‐29, HepG2, A549, Jurkat, HTB‐140, DU145, and PC‐3. We used MCF7 cells as the HDBC model, LNCaP cells as the HDPC model and the normal cells of the relevant tissues.…”

2-Hydroxymelatonin, a Predominant Hydroxylated Melatonin Metabolite in Plants, Shows Antitumor Activity against Human Colorectal Cancer Cells

“…Invasion assays were performed in Boyden chambers (Corning, New York, NY, USA). Transwell chambers pre-coated with 1% gelatin were used, as previously described [ 29 ]. Cells (2 × 10 6 ) in 120 μL of medium (DMEM containing 0.2% bovine serum albumin dissolved in PBS) containing or lacking various concentrations of melatonin or 2-hydroxymelatonin were seeded in the upper chamber.…”

Anticancer Potential of Lichens’ Secondary Metabolites

“…Secondary metabolites present in lichens include aliphatic, cycloaliphatic, aromatic, and terpenic compounds, which demonstrate significant biological and pharmacological effects including those of anti-inflammatory, antiviral, antibacterial, analgesic, antipyretic, anti-proliferative, and cytotoxic [17]. These compounds have demonstrated also antineoplastic activities in preclinical research in which revealed significant effects against cancer cells [18][19][20][21][22].…”