Abstract
Perinereis aibuhitensis peptide (PAP) is a decapeptide (Ile-Glu-Pro-Gly-Thr-Val-Gly-Met-Met-Phe, IEPGTVGMMF) with anticancer activity that was purified from an enzymatic hydrolysate of Perinereis aibuhitensis. In the present study, the anticancer effect of PAP on H1299 cell proliferation was investigated. Our results showed that PAP promoted apoptosis and inhibited the proliferation of H1299 cells in a time- and dose-dependent manner. When the PAP concentration reached 0.92 mM, more than 95% of treated cells died after 72 h of treatment. Changes in cell morphology were further analyzed using an inverted microscope and AO/EB staining and flow cytometry was adopted for detecting apoptosis and cell cycle phase. The results showed that the early and late apoptosis rates of H1299 cells increased significantly after treatment with PAP and the total apoptosis rate was significantly higher than that of the control group. Moreover, after treatment with PAP, the number of cells in the S phase of cells was significantly reduced and the ability for the cells to proliferate was also reduced. H1299 cells were arrested in the G2/M phase and cell cycle progression was inhibited. Furthermore, the results of western blotting showed that nm23-H1 and vascular endothelial growth factor (VEGF) protein levels decreased in a dose-dependent manner, while the pro-apoptotic protein and anti-apoptotic protein ratios and the level of apoptosis-related caspase protein increased in a dose-dependent manner. In conclusion, our results indicated that PAP, as a natural marine bioactive substance, inhibited proliferation and induced apoptosis of human lung cancer H1299 cells. PAP is likely to be exploited as the functional food or adjuvant that may be used for prevention or treatment of human non-small cell lung cancer in the future.
Highlights
Primary bronchogenic carcinoma is referred to as lung cancer and can occur at various levels of the bronchial epithelium or glands in the form of a malignant tumor [1]
To further verify the effects of Perinereis aibuhitensis peptide (PAP) on H1299 cells and explain the underlying mechanisms, western blotting was used to investigate the expression of apoptosis-related proteins in mechanisms, western blotting was used to investigate the expression of apoptosis-related proteins in treated H1299 cells
PAP (Ile-Glu-Pro-Gly-Thr-Val-Gly-Met-Met-Phe, IEPGTVGMMF) that was purified from an enzymatic hydrolysate of Perinereis aibuhitensis showed anti-cancer activity toward
Summary
Primary bronchogenic carcinoma is referred to as lung cancer and can occur at various levels of the bronchial epithelium or glands in the form of a malignant tumor [1]. The incidence and mortality of lung cancer have increased year by year and lung cancer is a disease that seriously threatens human health and life. According to statistics from the United Nations and the European Union, the lung cancer is the most common cause of cancer death, with an estimated 388,000 lung cancer cases resulting in death in Europe in 2018 [2]. According to the American Cancer Society’s 2018 report, the numbers of new cancer diagnoses and cancer deaths in the United States in 2018 are estimated to be. Mar. Drugs 2019, 17, 122; doi:10.3390/md17020122 www.mdpi.com/journal/marinedrugs.
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