scholarly journals Antioxidant Activity and Antiproliferative Effects of Lycium barbarum’s (Goji berry) Fractions on Breast Cancer Cell Lines

Folia Medica ◽  
2019 ◽  
Vol 61 (1) ◽  
pp. 104-112 ◽  
Author(s):  
Kaloyan D. Georgiev ◽  
Iliya J. Slavov ◽  
Ivan A. Iliev

Abstract Background: Lycium barbarum has gained immense popularity over the past decade because of its antioxidant properties. There are many reports of observed health benefits of juice consumption, including prophylaxis in neoplastic disease and treatment of tumors. Materials and methods: In this study, we isolated three fractions of Lycium barbarum fruits – total water, pectin-free and polysaccharide, and determined their antioxidant activity by ORAC and HORAC assays. We investigated the antiproliferative effects of Lycium barbarum’s pectin-free and polysaccharide fraction on three different breast cell lines - MCF-10A (non-tumorigenic epithelial breast cell line), MCF-7 (breast cancer cell line, estrogen, progesterone receptors +, HER2-), and MDA-MB-231 (breast cancer cell line, triple negative), by the MTT dye reduction assay. Results: The Lycium barbarum’s pectin-free fraction showed concentration-dependent growth inhibition on the three cell lines, moreover, on cancer cells (MCF- 7 and MDA-MB-231) it was significantly more pronounced. The polysaccharide fraction showed negligible activity on the three cell lines, only the highest concentration (1000 μg/mL), suppressed the proliferation of MCF-7 cells. The combination of pectin-free and polysaccharide fraction on MCF-7 did not show the expected synergistic effect. Conclusion: We found a relative correlation between the polyphenolic content of the extracts and the observed effects. The pectin-free extract had the highest content of polyphenols with the best antioxidant and antineoplastic activity against breast cancer cells. Addition of polysaccharide to the pectin-free fraction contributes to its pharmacological activity.

2021 ◽  
Author(s):  
Maged Mostafa Mahmoud ◽  
Ahmed M. Al-Hejin ◽  
Turki S. Abujamel ◽  
Modhi Alenezi ◽  
Fadwa Aljoud ◽  
...  

Abstract This study served as the pioneer in studying the anti-cancer role of chicken cathelicidin peptides. Chicken cathelicidins were used as anticancer agent against the breast cancer cell line (MCF-7) and human colon cancer cell line (HCT116). An in vivo investigation was also achieved to evaluate the role of chicken cathelicidin in Ehrlich ascites cell (EAC) suppression as a tumor model after subcutaneous implantation in mice. In addition, the mechanism of action of the interaction of cationic peptides with breast cancer cell line MCF-7 was also investigated. It was found during the study that exposure of cell lines to higher concentration of chicken cathelicidin for 72 h reduced cell lines growth rate by 90%-95%. These peptides demonstrated down-regulation of (cyclin A1 and cyclin D genes) which are essential for G1/S phase transient and S/G2 phase and consequently causes “prometaphase arrest” ultimately leading to death of MCF-7 cells. The study showed two- and three-times higher expression of the caspase-3, and − 7 genes respectively in MCF-7 cells treated with chicken peptides (especially cathelicidin-2 and − 3) relative to untreated cells which encouraged pro-apoptotic pathway, autophagy, and augmentation of the anti-proliferative activity. Our data showed that chicken ( CATH-1 ) enhance releasing of TNFα, INF-γ and upregulation of granzyme K in treated mice groups, in parallel, the tumor size and volume was reduced in the treated EAC-bearing groups after cathelicidin administration compared to untreated EAC-bearing group. Additionally, animals received high dose of cathelicidin-1 (40 µg/ml) displayed an apical survival rate compared to untreated carcinoma control and animals which received low dose of cathelicidin (10 and 20 µg/ml). Tumor of mice groups treated with chicken cathelicidin displayed high area of necrosis compared to untreated EAC-bearing mice. Based on histological analysis and immunohistochemical staining revealed that the tumor section in Ehrlich solid tumor exhibited a strong Bcl2 expression in untreated control compared to mice treated with 10 & 20 µg/ml of cathelicidin. Interestingly, low expression of Bcl2 were observed in mice taken 40 µg/ml of CATH-1. This study drive intention in treatment of cancer through the efficacy of anticancer efficacy of chicken cathelicidin peptides.


2020 ◽  
Vol 20 (9) ◽  
pp. 1072-1086
Author(s):  
Stephanie B. Arulnathan ◽  
Kok H. Leong ◽  
Azhar Ariffin ◽  
Huda S. Kareem ◽  
Kevin K.H. Cheah

Background: Oxadiazoles, triazoles, and their respective precursors have been shown to exhibit various pharmacological properties, namely antitumour activities. Cytotoxic activity was reported for these compounds in various cancer cell lines. Aim and Objectives: In this study, we aim at investigating the mechanism of apoptosis by N-(4-chlorophenyl)-2-(4- (3,4,5-trimethoxybenzyloxy)benzoyl)-hydrazinecarbothioamide, a triazole precursor, henceforth termed compound P7a, in breast cancer cell line, MCF-7. We first screen a series of analogues containing (3,4,5-trimethoxybenzyloxy) phenyl moiety in breast cancer cell lines (MCF-7 and MDA-MB-231) to select the most cytotoxic compound and demonstrate a dose- and time-dependent cytotoxicity. Then, we unravel the mechanism of apoptosis of P7a in MCF-7 as well as its ability to cause cell cycle arrest. Methods: Synthesis was performed as previously described by Kareem and co-workers. Cytotoxicity of analogues containing (3,4,5-trimethoxybenzyloxy)phenyl moiety against MCF-7 and MDA-MB-231 cell lines was evaluated using the MTS assay. Flow cytometric analyses was done using Annexin V/PI staining, JC-1 staining and ROS assay. The activity of caspases using a chemoluminescence assay and western blot analysis was conducted to study the apoptotic pathway induced by the compound in MCF-7 cells. Lastly, cell cycle analysis was conducted using flow cytometry. Results: Upon 48 hours of treatment, compound P7a inhibited the proliferation of human breast cancer cells with IC50 values of 178.92 ± 12.51μM and 33.75 ± 1.20μM for MDA-MB-231 and MCF-7, respectively. Additionally, compound P7a showed selectivity towards the cancer cell line, MCF-7 compared to the normal breast cell line, hTERT-HME1, an advantage against current anticancer drugs (tamoxifen and vinblastine). Flow cytometric analyses using different assays indicated that compound P7a significantly increased the proportion of apoptotic cells, increased mitochondria membrane permeabilisation and caused generation of ROS in MCF-7. In addition, cell cycle analysis showed that cell proliferation was arrested at the G1 phase in the MCF-7 cell line. Furthermore, upon treatment, the MCF-7 cell line showed increased activity of caspase-3/7, and caspase-9. Lastly, the western blot analysis showed the up-regulation of pro-apoptotic proteins along with up-regulation of caspase-7 and caspase-9, indicating that an intrinsic pathway of apoptosis was induced. Conclusion: The results suggest that compound P7a could be a potential chemotherapeutic agent for breast cancer.


Author(s):  
C.M. Noorjahan ◽  
T. Saranya

An investigation was carried out to study the antioxidant, anticancer and docking activities of medicinal plant, Tulsi – Ocimum sanctum. The results of antioxidant activity of Tulsi leaves extract showed that tulsi leaves has good free radical scavenging ability and IC50 value was found to be 54.23% at 500 µg/ml. The results of anticancer activity of Ocimum santum on normal VERO cell and MCF-7 cell line has showed good anticancer activity having the IC50 concentration at 51.1 ì|g/ml against MCF-7 cell lines – Human Breast cancer cell line thereby indicating that the percentage of cell viability increases with the increased concentration of Ocimum santum (Tulsi) whereas 24.4% cell viability was recorded in the normal VERO cell line. DNA laddering assay was performed on agarose gel electrophoresis. A clear fragmented DNA ladders were observed in tulsi treated MCF-7– Human Breast cancer cell lines. But the untreated normal VERO cell lines did not show any DNA fragmentation. Thereby confirms that Ocimum sanctum induced cell death on breast cancer cell line MCF-7 cancerous cell through apoptosis. Molecular docking was carried out (AutoDock tools), Docking simulations was performed using Lamarckian genetic algorithm of Solis and Wests local search method. Interaction between HDAC6 and Cirsilileon possessing binding energy showed +15.91kcal for interaction studies. It was found that most of the hydrogen bonding is with the residues TYR 76, TRP 35, SER 67, TYR 81, GLU 33, TYR 48, ILE 69 and MET 53 present in the binding pocket. The ligand was docked with the target protein, and the best docking poses were identified and the binding poses of the cirsilieon was shown. This act as the best docking poses shows how the ligand molecule fits into the binding region of the target protein.


2018 ◽  
Vol 18 (4) ◽  
pp. 573-582 ◽  
Author(s):  
Khaled R.A. Abdellatif ◽  
Mostafa M. Elbadawi ◽  
Mohammed T. Elsaady ◽  
Amer A. Abd El-Hafeez ◽  
Takashi Fujimura ◽  
...  

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefania Nobili ◽  
Antonella Mannini ◽  
Astrid Parenti ◽  
Chiara Raggi ◽  
Andrea Lapucci ◽  
...  

AbstractInvasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women’s health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER−/PR−/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24−/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within − 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.


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