Lotus ( Nelumbo nucifera ) seedpod extract inhibits cell proliferation and induces apoptosis in non‐small cell lung cancer cells via downregulation of Axl

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.

Lotus (Nelumbo nucifera Gaertn.) and Its Bioactive Phytocompounds: A Tribute to Cancer Prevention and Intervention

“…The extract also induced apoptosis through increased cleavage of PARP and increased phosphorylation of H2A histone family member X (γ-H2AX). Additionally, the extract-treated cells showed the ability to reduce the expression of mRNA and protein of Axl in both cell lines, indicating that Axl is a novel therapeutic target of the antiproliferative and proapoptotic activities of N. nucifera [121].…”

Phytochemicals, biological activity, and industrial application of lotus seedpod (Receptaculum Nelumbinis): A review

“…Lotus seedpods extracts have been demonstrated to possess antioxidation ( 8 , 9 , 13 , 14 , 29 , 34 – 36 ), anti-cancer ( 8 , 14 , 32 ), anti-melanogenic ( 27 , 33 ), anti-inflammatory ( 28 , 31 ), anti-irradiation ( 37 ), cardioprotection ( 30 ) and hepatoprotection ( 26 ) bioactivities, as displayed in Figure 3A and Supplementary Table 1 .…”

“…Ethanol extracts from lotus seedpods have been indicated to exhibit antioxidation ( 8 , 29 , 34 , 35 ), anti-cancer ( 8 , 32 ), anti-melanogenic ( 33 ) and anti-inflammatory ( 31 ) actions.…”

“…A cell experiment has shown that the ethanol extracts revealed cytoprotection on H 2 O 2 -induced RAW264.7 cells and reduced MDA level ( 34 ). In terms of anti-cancer activity, ethanol extracts from lotus seedpods exerted anti-proliferation effect on HepG2, LNcap, A549 and H460 cells ( 8 , 32 ). Thereinto, the extracts induced cell apoptosis of A549 and H460 cells via downregulation of Axl, illustrating as increase of cleavage PARP and γ-H2AX protein expressions, and decrease of PARP protein expression as well as Axl protein and mRNA expressions ( 32 ).…”

Extraction optimization, physicochemical property, antioxidant activity, and α‐glucosidase inhibitory effect of polysaccharides from lotus seedpods

“…Because only a small quantity of lotus seedpods is used as the main constituent of an edible fungal medium, significant waste of resources and heavy environmental pollution are caused. Recently, lotus seedpod extracts have been reported to exhibit various biological activities, such as anticancer, 5 anti‐inflammatory, 6 radioprotective, 7 and lipid‐lowering 8 actions. This might be explained by the abundant bioactive compounds they contain, including proanthocyanidins, 9 polyphenols, 10 and flavonoids 3 .…”