scholarly journals An Extract of Olive Mill Wastewater Downregulates Growth, Adhesion and Invasion Pathways in Lung Cancer Cells: Involvement of CXCR4

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 ◽  
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.


Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 247
Author(s):  
Eun-Ju Jang ◽  
Jee Young Sung ◽  
Ha-Eun Yoo ◽  
Hyonchol Jang ◽  
Jaegal Shim ◽  
...  

Anoikis is a type of apoptosis induced by cell detachment from the extracellular matrix (ECM), which removes mislocalized cells. Acquisition of anoikis resistance is critical for cancer cells to survive during circulation and, thus, metastasize at a secondary site. Although the sensitization of cancer cells to anoikis is a potential strategy to prevent metastasis, the mechanism underlying anoikis resistance is not well defined. Although family with sequence similarity 188 member B (FAM188B) is predicted as a new deubiquitinase (DUB) member, its biological function has not been fully studied. In this study, we demonstrated that FAM188B knockdown sensitized anoikis of lung cancer cell lines expressing WT-EGFR (A549 and H1299) or TKI-resistant EGFR mutant T790M/L858R (H1975). FAM188B knockdown using si-FAM188B inhibited the growth of all three human lung cancer cell lines cultured in both attachment and suspension conditions. FAM188B knockdown resulted in EGFR downregulation and thus decreased its activity. FAM188B knockdown decreased the activities of several oncogenic proteins downstream of EGFR that are involved in anoikis resistance, including pAkt, pSrc, and pSTAT3, with little changes to their protein levels. Intriguingly, si-FAM188B treatment increased EGFR mRNA levels but decreased its protein levels, which was reversed by treatment with the proteasomal inhibitor MG132, indicating that FAM188B regulates EGFR levels via the proteasomal pathway. In addition, cells transfected with si-FAM188B had decreased expression of FOXM1, an oncogenic transcription factor involved in cell growth and survival. Moreover, FAM188B downregulation reduced metastatic characteristics, such as cell adhesion, invasion, and migration, as well as growth in 3D culture conditions. Finally, tail vein injection of si-FAM188B-treated A549 cells resulted in a decrease in lung metastasis and an increase in mice survival in vivo. Taken together, these findings indicate that FAM188B plays an important role in anoikis resistance and metastatic characteristics by maintaining the levels of various oncogenic proteins and/or their activity, leading to tumor malignancy. Our study suggests FAM188B as a potential target for controlling tumor malignancy.


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.


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.


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