Eryngium billardieri Extract and Fractions Induces Apoptosis in Cancerous Cells

Author(s):  
Samira Hasanbeiglu ◽  
Kamran Hosseini ◽  
Ommoleila Molavi ◽  
Parina Asgharian ◽  
Vahideh Tarhriz

Background: Eryngium is genus flowering plants in the Umbelliferae family having pharmacological properties such as anti-inflammatory and anti-diabetic. Given the nature of melanoma and breast cancers in recent years and the fact that the anti-cancer properties of Eryngium billardieri on mentioned cell lines have not been studied, the present study conducted to explore these properties. Objective: The mechanisms of cytotoxicity and apoptosis of aerial parts of various extracts and fractions of E. billardieri on cancerous cells and normal cells were investigated. Methods: Samples were collected from natural habitats, dried and then extracted by Soxhlet apparatus with solvents of n-Hex, DCM and methanol, respectively. The cytotoxic effects of the extracts were investigated by MTT method on MCF7, B16 and HFF-2 classes for 24 and 48 hours. Flowcytometry, was also used to investigate the mechanism of cytotoxicity and confirming by Real-time PCR of p53 and Bax genes, which codes apoptosis regulator proteins. Meanwhile, volatile compounds of extracts were identified by GC-MS method. Results: The obtained data showed that the n-Hex extract of E. billardieri on B-16 and MCF7 cell lines and dichromethane extract on MCF7 cell line had the most significant cytotoxic effect compared to DMSO control (p value <0.001). Our finding showed that the mechanism of n-Hex extract with 80% and 100% vlc fractions on B16 induced apoptotic compared to HFF-2 control cells, moreover, n-Hex extract and 80% vlc fraction on MCF7 was apoptotic. The major compounds of n-Hex, DCM and 80% and 100% fractions of n-Hex extract obtained from GC-MS are non-terpenoid. Conclusion: Non-terpenoids compounds of E. billardieri can be the responsible for showing the most cytotoxic effects on MCF7 and B16 cell lines with apoptotic mechanism and n-Hex extract had the most significant inhibitory effect on cancerous cells compared to the HFF-2 control cells by the mechanism of apoptosis.

2021 ◽  
Vol 12 ◽  
Author(s):  
Gaoran Liu ◽  
Ruiyun Huo ◽  
Yanan Zhai ◽  
Ling Liu

Three new secondary metabolites pestalothenins A–C (1–3), including two new humulane-derived sesquiterpeniods (1 and 2) and one new caryophyllene-derived sesquiterpeniod (3), together with five known compounds (4–8) were isolated from the crude extract of the plant endophytic fungus Pestalotiopsis theae (N635). Their structures were elucidated by the extensive analyses of HRESIMS and NMR spectroscopic data. The absolute configurations of 1–3 were determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The cytotoxic effects of these compounds were evaluated in vitro. Compound 6 showed moderate cytotoxicity against T24 and MCF7 cell lines. In addition, compounds 1–8 were also evaluated for antibacterial activity.


2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 26-26
Author(s):  
Aisulu Zhussupova ◽  
Tetsu Hayashida ◽  
Maiko Takahashi ◽  
Hiromitsu Jinno ◽  
Yuko Kitagawa

26 Background: HOXB9 is a member of class I HOX genes and is known to be overexpressed in human breast cancer and related to EMT, tumor angiogenesis, and radio-resistance (PNAS 2010), being significant prognostic factor in breast cancer patients. (Ann Surg Oncol 2012). Methods: We analyzed the upstream promoter region to determine the critical sequence for HOXB9 transcription. The multiple lengths of HOXB9 promoter region were cloned into pGL3 luciferase vector and each of them were checked by luciferase assay. Then made E2F1 overexpressed cell-lines: MCF7, MCF10A and MDA-MB231 to check HOXB9 gene expression. ChIP assay performed using E2F1 induced MCF7 cell-line model and EMSA made with T47D cells and E2F1 antibody. Results: We demonstrated luciferase activity of MDA-MB231 cells and overexpressed HOXB9 was determined at the region from -404 to -392 bps, showing that the mentioned region plays the critical role for the transcription of HOXB9. Computer prediction system for the binding ability to critical sequence raised several candidate: E2F1, PAX-5, P53, ETS-1, NFY-A, Sp-1, which are known to be related with cancer progression and we confirmed these genes could induce HOXB9. E2F1 overexpressed breast cancer cell-lines indicate high expression of HOXB9 show the correlation between E2F1 and HOXB9 expression. Luciferase assay method done by constructing pGL3 with HOXB9 critical sequence and analyzed using wild-type MCF7 and E2F1 induced MCF7 cells showed high luciferase activity of HOXB9 critical sequence plasmid in E2F1 induced MCF7 cell-line by compare to WT. ChIP assay and EMSA assay methods performed using E2F1 overexpressed MCF7 and T47D cell-lines model revealed high precipitation rate with E2F1 antibody and HOXB9 expression than negative control. Conclusions: HOXB9 is plays the role as the accelerator of breast cancer progression and discovering the properties of the gene and related factors will help to understand new signaling pathways of breast cancer development. E2F1 is a strong candidate direct binds to HOXB9 critical sequence and correlates with HOXB9 expression. Manipulating of E2F1 expression may regulate HOXB9 and reduce cancer progression and metastasis.


Proceedings ◽  
2017 ◽  
Vol 1 (10) ◽  
pp. 1077 ◽  
Author(s):  
Esra Köngül ◽  
Ömer Taş ◽  
Leyla Paşayeva ◽  
Gökçe Şeker Karatoprak

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 575-575
Author(s):  
Yonghui Yang ◽  
Joseph Gera ◽  
Alan Lichtenstein

Abstract Abstract 575 DEPTOR is an mTOR binding protein specifically over-expressed in some genetic subtypes of multiple myeloma (MM). DEPTOR binds mTOR in TORC1 and TORC2 complexes and inhibits their kinase activity. As a result, p70 and 4E-BP1 phosphorylation, substrates of TORC1, are decreased. However, TORC1/p70 down-regulation results in marked feedback activation of the PI3K/AKT pathway and AKT becomes activated even though DEPTOR restrains TORC2. Most importantly, DEPTOR knockdown is deleterious to over-expressing MM cell lines, resulting in apoptosis. We hypothesized that compounds preventing DEPTOR-mTOR association would have cytotoxic effects in these cell lines, comparable to DEPTOR knockdown. We, thus, developed a yeast two-hybrid assay where survival of yeast in histidine-depleted media depended upon an association between DEPTOR and mTOR in genetically engineered yeast. After demonstrating a robust yeast two-hybrid protein interaction, yeast were screened against the NCI small inhibitor library (>150,000 compounds) and six compounds were identified that inhibited the interaction. These compounds rapidly increased p70 phosphorylation in MM cell lines in a concentration-dependent fashion, consistent with an inhibition of DEPTOR's inhibitory effect on mTORC1. Co-immunoprecipitation confirmed the compounds inhibited binding of DEPTOR to mTOR without effects on an mTOR-RICTOR interaction. The compounds also significantly inhibited cell survival of cell lines and they were at least 10 × fold more effective against DEPTOR over-expressing MM lines (8226, OPM-2, MM1.S) versus non-expressing lines (U266, FR4, delta 47). These results support a drug development strategy for myeloma that focuses on preventing DEPTOR binding to mTOR within TORC complexes for subsequent anti-myeloma cytotoxic effects. Disclosures: No relevant conflicts of interest to declare.


Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2459 ◽  
Author(s):  
Laura G. Sarbu ◽  
Sergiu Shova ◽  
Dragos Peptanariu ◽  
Isabela A. Sandu ◽  
Lucian M. Birsa ◽  
...  

Background: Due to the emergence of multidrug resistant microorganisms, new classes of antibiotics are needed. In this paper, we present the cytotoxic effects of five tricyclic flavonoids, one of which was previously identified as a potent antimicrobial agent. Methods: All five derivatives were tested against human HOS and MCF7 cancer cell lines using a wound scratch assay. The cytotoxic properties of previously reported flavonoid 4a were also evaluated using the standard MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) and live/dead assays, using NHDF, HOS and MCF7 cell lines. Results: All five derivatives were found to inhibit to some degree the proliferation of cancer cells. 4a was also found to be less toxic towards regular versus cancerous human cells. Moreover, the minimum bactericidal concentration of 4a against Staphylococcus aureus was found to be non-toxic for any of the tested human cell lines. Conclusions: Derivative 4a has the potential of being used as a therapeutic agent against certain microorganisms. Further structure optimization is required for use against tumors.


2016 ◽  
Vol 11 (3) ◽  
pp. 1934578X1601100
Author(s):  
Janet Piloto Ferrer ◽  
Iris Catiana Zampini ◽  
Ana Soledad Cuello ◽  
Marbelis Francisco ◽  
Aylema Romero ◽  
...  

Xanthium strumarium L., the main species of the genus Xanthium, is ubiquitously distributed. The aim of this study was to determine the cytotoxic effect of aerial organs of X. strumarium, grown in Cuba, against cancer cell lines and the isolation of compounds potentially responsible for this activity. Initially, an ethanol partitioning procedure yielded the XSE extract that was subsequently fractionated with chloroform resulting in a XSCF fraction. Both, XSE and XSCF fractions exhibited cytotoxic effects on MDA MB-231, MCF7, A549 and CT26 cell lines by using the MTT assay. Above all, the XSCF fraction was more active than XSE. For this reason, XSCF was subsequently fractionated by silica gel chromatography and the active fractions submitted to semi-preparative HPLC for isolation of bioactive compounds. Six sub-fractions (SF1 to SF6) were recovered. Sub-fractions 3 and 6 were the most active on each assayed cell line, while sub-fractions 4 and 5 were only active against A549 and CT26 cell lines. In each case, sub-fraction 6 showed the strongest inhibitory effect. The HPLC-DAD fingerprint of sub-fraction 6 showed a single peak that was identified by GC-MS as (-) spathulenol, a sesquiterpene with reported antitumor activity.


MedChemComm ◽  
2016 ◽  
Vol 7 (5) ◽  
pp. 837-844 ◽  
Author(s):  
Debanjana Chakraborty ◽  
Chetan Kumar Jain ◽  
Arindam Maity ◽  
Shekhar Ghosh ◽  
Susanta Roy Choudhury ◽  
...  

Desgalactotigonin and oleanolic acid 3-O-β-d-glucuronide were isolated from Chenopodium album and were evaluated for cytotoxic activity against various cancer cell lines.


Proceedings ◽  
2017 ◽  
Vol 1 (10) ◽  
pp. 1055 ◽  
Author(s):  
Leyla Paşayeva ◽  
Esra Köngül ◽  
Rojen Geylan ◽  
Gökçe Şeker Karatoprak ◽  
Osman Tugay

Author(s):  
Zeinab Abedian ◽  
Niloofar Jenabian ◽  
Ali Akbar Moghadamnia ◽  
Ebrahim Zabihi ◽  
Roghayeh Pourbagher ◽  
...  

Objective/ Background: Cancer is still the most common cause of morbidity in world and new powerful anticancer agents without severe side effects from natural sources is important. Methods: The evaluation of cytotoxicity and apoptosis induction was carried out in MCF-7,HeLa and Saos-2 as cancerous cell lines with different histological origin and human fibroblast served as control normal cell. The cells were treated with different concentrations of chitosan and the cytotoxicity was determined using MTT assay after 24, 48 and 72 h .The mode of death was evaluated by flow cytometry . Results: While both types of chitosan showed significant concentration-dependently cytotoxic effects against the three cancerous cell lines, fibroblast cells showed somehow more compatibility with chitosan. On the other hand, there were no significant differences between LMWC and HMWC cytotoxicity in all cell lines. The flow cytometry results showed the apoptosis pattern of death more in Saos-2 and HeLa while necrosis was more observable with MCF7. Also higher viability with both types of chitosan was seen in fibroblast as normal cells Conclusion: Chitosan shows anticancerous effect against 3 cancerous cell lines, while it is compatible with normal diploid fibroblast cells. Furthermore, it seems that the molecular weight of chitosan does not affect its anticancerous property.


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