Anti-proliferative and apoptosis-inducing effects of matricin on human non-small cell lung cancer H1299 cells via MAPK pathway activation

Abstract

Lung cancer in humans is majorly represented by non-small cell lung cancer cells, and there is a constant search for an efficient therapeutic approach. This study aims to find the anti-proliferative and apoptotic effects of matricin on H1299 cells via activation of MAPK pathway. Non-small cell H1299 cells were subjected to viability analysis with MTT assay and anti-proliferation analysis with different concentrations of matricin. Apoptosis was determined with annexin V/propidium iodide (PI) and flow cytometric analysis. Analysis of oxidative stress markers, reduced glutathione, lipid peroxidation (LPO), superoxide dismutase (SOD), and catalase (CAT) activities were done using standard assay kits. Apoptosis enzymes caspase-3, caspase-8, and caspase-9 levels were measured using colorimetric kit analysis. Western blot analysis on apoptotic proteins was performed to determine the involvement of MAPK pathway activation in apoptosis. Matricin significantly ( P < 0.01) exerted anti-proliferative activities on H1299 cells in a dose-dependent manner. Flow cytometric apoptosis analysis showed increasing concentrations of matricin had increased apoptosis ( P < 0.01) in the H1299 cells. Levels of oxidative stress markers were altered significantly ( P < 0.01) by matricin. Caspase-3, caspase-8, and caspase-9 levels were significantly increased ( P < 0.01) in matricin-treated H1299 cells. Western blot analysis showed decreased expression of anti-apoptotic Bcl-2, increased expressions of Bax and phosphorylated JNK, ERK 1/2, and p-38 MAPK proteins in matricin-treated H1299 cells. Matricin has significant anti-proliferative and apoptosis-inducing effects via activation of MAPK pathway in non-small cell lung cancer cells.

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“…These effects lead to the increase in apoptotic factors and the reduction of metastasis, cellular invasion and anti-apoptotic factors. Illustratively, earlier study demonstrated the potentiality of matricin to significantly exert anti-proliferative and apoptosis-inducing effects in non-small cell lung cancer cells via activation of MAPK pathway [ 61 ]. Additionally, expression of anti-apoptotic proptein Bcl-2 was significantly decreased while the level of pro-apoptosis protein Bax as well as the activity of apoptosis marker enzymes caspase-9, caspase-8 and caspase-3 were significantly increased.…”