Journal Article

Lichen Secondary Metabolite, Physciosporin, Inhibits Lung Cancer Cell Motility

Jeong, Min-Hye, Hur, Jae-Seoun, Kim, Hangun, Udeni, Jayalal, Yu, Young Hyun, Ha, Hyung-Ho, Kim, Kyung Keun, Nguyen, Tru Van, Moon, Cheol, Sun, Eun Gene, Nguyen, Thanh Thi, Park, So-Yeon, Yang, Yi, Pereira, Iris

2015

Overview

Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. & Taylor) D.J. Galloway & P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin)-mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3'-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acetone / Acetone - chemistry / Antineoplastic Agents - isolation & purification / Antineoplastic Agents - metabolism / Antineoplastic Agents - pharmacology / Cadherin / Cadherins / Cancer / Care and treatment / Carrier Proteins - genetics / Carrier Proteins - metabolism / Cdc42 protein / Cell adhesion & migration / Cell Line, Tumor / Cell migration / Cell Movement - drug effects / Chromatography / Epidermal growth factor / Epithelial-Mesenchymal Transition - drug effects / Gene expression / Gene Expression Regulation, Neoplastic - drug effects / Genetic aspects / Humans / Kangai-1 Protein - genetics / Kinases / Lichens / Lichens - metabolism / Lung cancer / Lung diseases / Lung Neoplasms - pathology / Medical prognosis / Medical research / Membrane Proteins - genetics / Membrane Proteins - metabolism / Mesenchyme / Metabolites / Metastases / Metastasis / Motility / mRNA / N-Cadherin / National parks / Neoplasm Invasiveness / Neoplasm Metastasis / NMR / Nuclear magnetic resonance / Oxepins - isolation & purification / Oxepins - metabolism / Oxepins - pharmacology / Pharmaceutical sciences / Pharmacy / Physiological aspects / Plant Extracts - isolation & purification / Plant Extracts - pharmacology / Plant metabolites / Prostate cancer / Rac1 protein / rho GTP-Binding Proteins - metabolism / Secondary metabolites / Solvents / Transcription Factor AP-1 - metabolism / Transcription factors