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Lotus ( Nelumbo nucifera ) seedpod extract inhibits cell proliferation and induces apoptosis in non‐small cell lung cancer cells via downregulation of Axl
Author(s) -
Kim NamYi,
Yang InJun,
Kim Soyoung,
Lee ChuHee
Publication year - 2021
Publication title -
journal of food biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.507
H-Index - 47
eISSN - 1745-4514
pISSN - 0145-8884
DOI - 10.1111/jfbc.13601
Subject(s) - cell growth , apoptosis , biology , downregulation and upregulation , gene knockdown , cancer research , cancer cell , clonogenic assay , cell , microbiology and biotechnology , cancer , biochemistry , gene , genetics
Abstract Non‐small‐cell lung cancer (NSCLC) is the most frequent cause of cancer‐related death. In this study, we found the anticancer activity of lotus seedpod extract (LSPE) in NSCLC cells, since LSPE treatment inhibited cell proliferation of A549 and H460 cells in a dose‐dependent manner and the clonogenic activities of LSPE‐treated cells were also reduced. In LSPE‐treated cells, the cleavage of poly (ADP‐ribose) polymerase (PARP) and phosphorylation of H2X, were also observed, indicating the pro‐apoptotic effect of LSPE. Next, we found that LPSE treatment diminished the levels of protein and mRNA of Axl, a receptor tyrosine kinase (RTK) that transduces critical signals for cell proliferation and inhibition of apoptosis. The promoter activity of Axl was found to be dose‐dependently decreased in response to LSPE treatment, implying that LSPE inhibited Axl gene expression at transcriptional level. In addition, Axl overexpression was found to decrease the effects of LSPE on inhibition of cell proliferation and colony formation as well as induction of PARP cleavage and phosphorylation of H2AX, while the same activities of LPSE were increased by knockdown of Axl gene expression, indicating that the antiproliferative and pro‐apoptotic effect of LSPE is inversely proportional to the protein level of Axl. Taken together, we found that the LSPE suppressed cell proliferation and induced apoptosis of NSCLC cells, which is attenuated or augmented by overexpression or RNA interference of Axl expression, respectively. Our data suggest that Axl is a novel therapeutic target of LSPE to inhibit cell proliferation and promote apoptosis in NSCLC cells. Practical applications In this study, lotus seedpod extract (LSPE) was found to have the cytotoxic and apoptosis‐inducing potentials in non‐small‐cell lung cancer (NSCLC) cells. LSPE downregulated the Axl expression at transcriptional level and the effects of LSPE on cell proliferation as well as apoptosis were affected by Axl protein level. Therefore, the inference of Axl‐mediated intracellular signals by LSPE must be a novel approach to control NSCLC. Since our data imply that LSPE contains bioactive compounds targeting Axl, further studies to elucidate these compounds might discover a potent therapeutic agent.