scholarly journals Bulnesia sarmientoi Supercritical Fluid Extract Exhibits Necroptotic Effects and Anti-Metastatic Activity on Lung Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3304 ◽  
Author(s):  
Heng-Long Wang ◽  
Jung-Che Chang ◽  
Li-Wen Fang ◽  
Hsia-Fen Hsu ◽  
Li-Chiun Lee ◽  
...  

Bulnesia sarmientoi (BS) has long been used as an analgesic, wound-healing and anti-inflammatory medicinal plant. The aqueous extract of its bark has been demonstrated to have anti-cancer activity. This study investigated the anti-proliferative and anti-metastatic effects of BS supercritical fluid extract (BSE) on the A549 and H661 lung cancer cell lines. The cytotoxicity on cancer cells was assessed by an MTT assay. After 72 h treatment of A549 and H661 cells, the IC50 values were 18.1 and 24.7 μg/mL, respectively. The cytotoxicity on MRC-5 normal cells was relatively lower (IC50 = 61.1 μg/mL). BSE arrested lung cancer cells at the S and G2/M growth phase. Necrosis of A549 and H661 cells was detected by flow cytometry with Annexin V-FITC/PI double staining. Moreover, the cytotoxic effect of BSE on cancer cells was significantly reverted by Nec-1 pretreatment, and BSE induced TNF-α and RIP-1 expression in the absence of caspase-8 activity. These evidences further support that BSE exhibited necroptotic effects on lung cancer cells. By wound healing and Boyden chamber assays, the inhibitory effects of BSE on the migration and invasion of lung cancer cells were elucidated. Furthermore, the chemical composition of BSE was examined by gas chromatography-mass analysis where ten constituents of BSE were identified. α-Guaiene, (−)-guaiol and β-caryophyllene are responsible for most of the cytotoxic activity of BSE against these two cancer cell lines. Since BSE possesses significant cytotoxicity and anti-metastatic activity on A549 and H661 cells, it may serve as a potential target for the treatment of lung cancer.

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 903 ◽  
Author(s):  
Matteo Gallazzi ◽  
Marco Festa ◽  
Paola Corradino ◽  
Clementina Sansone ◽  
Adriana Albini ◽  
...  

Several diet-derived compounds have been reported to exert antioxidant, anti-proliferative and anti-angiogenic effects in numerous cancers and could be beneficial in cancer prevention. Olive oil production involves the generation of an aqueous phase defined as olive mill wastewater (OMWW), a polluting effluent rich in soluble polyphenols. Here, we assessed the cancer preventive properties exerted by a purified extract of OMWW (A009) for its activity on lung cancer cell lines. Hydroxytyrosol, the most abundant polyphenol present in our A009 extracts, was used as reference molecule in the assays performed. Extracts from OMWW from two different olive oil cultivars were used. We found that the A009 extracts limit lung cancer cell proliferation in a dose and time dependent manner. These effects were associated with the induction of apoptosis. A009 extracts were effective in inhibiting adhesion capabilities on a fibronectin layer accompanied with a reduction in their ability to generate invasive sprouts in a Matrigel layer. The production of chemokine CXCL12 and CXCR4 receptor were reduced by treatment with the extracts. Also, A009 interfered with the production of proangiogenic and pro-inflammatory VEGF, CXCL8, and CCL2 (as detected by FACS analysis) in the lung cell lines. A009 extracts were able to decrease STAT3 phosphorylation in lung cancer cells. Our results show that A009 extracts reduced activities related to tumor cell behavior in lung cancer cell lines, suggesting that they could have a potential cancer preventive role.


2021 ◽  
Vol 12 (5) ◽  
pp. 6950-6959

Prunus cerasus L (Sour cherries) contain diverse secondary metabolites which exhibit various biological activities, including anticancer, antioxidant, and anti-inflammatory properties. The present study aimed to determine the anticancer efficacy of four compounds, quercetin, daidzin, rutin, and chlorogenic acid, isolated from Prunus cerasus fruit. The antiproliferative activity of four cherry isolates was determined against five different cancer cell lines (NCI-H322, A549, THP-1, MCF-7, and PC-3) by Tetrazolium bromide assay, followed by apoptosis Cell cycle analyses, mitochondrial membrane potential, cell migration test, and in vivo Ehrlich Ascites Carcinoma studies using potent bioactive lead. The cytotoxicity profile of the four molecules demonstrated that quercetin induced significant cell growth inhibition in all cancer cell lines with paramount 79% cytotoxicity against NCI-H322 lung cancer cells (IC50 value 24μM). Incubation of NCI-H322 cells with quercetin showed a concentration-dependent increase in hypo-diploid sub G0/G1 DNA fraction, exhibited consequential changes in nuclear morphology, and caused mitochondrial transmembrane potential loss of 60.3% augmented at 30 µM. Pertaining to in vivo potency, quercetin manifested 89% tumor inhibition at 50 mg/kg body weight in EAC-bearing mice. The current studies raise the potential usefulness of quercetin in chemoprevention against lung cancer cells and support its empirical use as a promising nutraceutical agent.


2021 ◽  
Author(s):  
Qiu Ren ◽  
Miao Tian ◽  
Lin Lin ◽  
li juan Zhang ◽  
jia wen Zhang ◽  
...  

Abstract Background Under normal physiological conditions, insulin exhibited a series of important biological functions. However, more and more evidence indicate that insulin is closely related to the occurrence and development of tumors. Recent studies have shown that insulin is also closely related to the occurrence and development of lung cancer. However, until now, the cellular properties of insulin/insulin receptors on lung cancer have not been fully revealed. Methods Indirect immunofluorescence, western-blot and other techniques have been used to identify the biological activity of insulin on lung cancer cell lines. Results The biological activity of insulin is closely related to its cell behavior. therefore we used lung cancer cell lines as a model to explore the cellular behavior and properties of insulin/IR in the current study, and the results showed that the IR can internalize into lung cancer cells, and it can also transport into the nucleus under insulin treatment. further study showed nuclear-localized IR could promote the proliferation of lung cancer cells. Taken together, this study shows that IR’s nuclear localization is closely related to cell proliferation. Conclusions This work lays the foundation for further research on relationship between insulin and the occurrence and development of lung cancer.


Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3790
Author(s):  
Gro Elise Rødland ◽  
Sissel Hauge ◽  
Grete Hasvold ◽  
Lilli T. E. Bay ◽  
Tine T. H. Raabe ◽  
...  

Inhibitors of WEE1 and ATR kinases are considered promising for cancer treatment, either as monotherapy or in combination with chemo- or radiotherapy. Here, we addressed whether simultaneous inhibition of WEE1 and ATR might be advantageous. Effects of the WEE1 inhibitor MK1775 and ATR inhibitor VE822 were investigated in U2OS osteosarcoma cells and in four lung cancer cell lines, H460, A549, H1975, and SW900, with different sensitivities to the WEE1 inhibitor. Despite the differences in cytotoxic effects, the WEE1 inhibitor reduced the inhibitory phosphorylation of CDK, leading to increased CDK activity accompanied by ATR activation in all cell lines. However, combining ATR inhibition with WEE1 inhibition could not fully compensate for cell resistance to the WEE1 inhibitor and reduced cell viability to a variable extent. The decreased cell viability upon the combined treatment correlated with a synergistic induction of DNA damage in S-phase in U2OS cells but not in the lung cancer cells. Moreover, less synergy was found between ATR and WEE1 inhibitors upon co-treatment with radiation, suggesting that single inhibitors may be preferable together with radiotherapy. Altogether, our results support that combining WEE1 and ATR inhibitors may be beneficial for cancer treatment in some cases, but also highlight that the effects vary between cancer cell lines.


Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5119
Author(s):  
Won-Chul Lim ◽  
Hyo-Kyung Choi ◽  
Kyung-Tack Kim ◽  
Tae-Gyu Lim

We sought to investigate the effect of rose petal extract (RPE) on the proliferation, migration, and invasion of cancer cells. RPE significantly inhibited the growth of lung and colorectal cancer cell lines, with rapid suppression of A549 lung cancer cells at low concentrations. These effects occurred concomitantly with downregulation of the cell proliferation mediators PCNA, cyclin D1, and c-myc. In addition, RPE suppressed the migration and invasion of A549 cells by inhibiting the expression and activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and -9). We hypothesize that the suppressive activity of RPE against lung cancer cell proliferation and early metastasis occurs via the EGFR-MAPK and mTOR-Akt signaling pathways. These early results highlight the significant potency of RPE, particularly for lung cancer cells, and warrant further investigation.


2020 ◽  
Vol 10 (4) ◽  
pp. 435-442
Author(s):  
Ruowen Zhang ◽  
Aihua Ren ◽  
Zhaohui Wang ◽  
Dawei Wang

Lung cancer is one kind of the malignant tumor with high mortality. And non-small cell lung cancer is the main subtype of lung cancer. And the proteins of CLCA family (CLCA1, CLCA2 and CLCA4) played an inhibitory role in the occurrence and development of multiple types of tumors. However, the effect of CLCA4 on non-small cell lung cancer cells remains unclear. In our study, we used the lentivirus to establish the overexpressed CLCA4 A549 cells. Next, the CCK-8 and clone formation assays were performed to detect the changes of proliferation of A549 cells. The wound healing and transwell assays were performed to determine the changing of the migration and invasion of A549 cells. Then gemcitabine was used to treat these cells and the CCK-8, wound healing and transwell assays were carried out to detect the effect of the combination of gemcitabine and the overexpression of CLCA4 on the proliferation, migration and invasion of A549 cells. After the overexpression of CLCA4, the clone formation and mobility of A549 cells was enhanced. Furthermore, the overexpression of CLCA4 induced the apoptosis of A549 cells and promoted the expression of apoptosis related proteins. The combination of gemcitabine and the overexpression of CLCA4 further suppressed the proliferation, migration and invasion of A549 cells. CLCA4 inhibited the proliferation, migration and invasion of non-small cell lung cancer cells. CLCA4 also strengthened the sensitivity of non-small cell lung cancer cells for gemcitabine.


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