Anti-cancer effect of Urginea maritima bulb extract invitro through cell cycle arrest and induction of apoptosis in human breast cancer cell lines

Author(s):  
Khadije Saket ◽  
Roshanak Salari ◽  
Ehsan Saburi ◽  
Mahdi Yousefi ◽  
Mohammad Ali Khodadoust ◽  
...  

Background: Breast cancer is the most common known malignancy in women and it is therefore very important to prevent and treat this cancer. In this experimental study, the anti-breast cancer effect of Urginea matrima was investigated. Method: Breast cancer cell lines [MCF-7 and MDA-MB231] and L929 normal cells [as a control group] were cultivated in DMEM medium. Bulb aqueous and hydroalcoholic extracts [70:30] were prepared through maceration method. The cultured cells were treated with different concentrations [6, 3, 1.5, 0.75, 0.375, 0.187 and 0.093 μg/mL] of U.maritima extracts for 24, 48 and 72 h. Toxicity of the extracts on cells were examined using MTT test. The Annexin V–FITC Apoptosis Detection Kit was used to evaluate apoptosis and necrosis. Flow cytometry technique was employed to evaluate the cell cycle and the cell migration was evaluated by Scratch method. Data were analyzed by GraphPad Prism and SPSS software and P <0.05 was considered significant. Result: Results showed that both extracts of U.maritima in the concentration of 1.5 and 3 μg/ ml at 24,48 and 72h presented cytotoxicity effect on MCF7 cell line . Also, both extracts in the concentration of 3 μg/ ml at 24 and 72h, and in the concentration of 6 μg/ ml at 72h showed cytotoxicity effect significantly on MDA-MB231 cells. In addition, the plant extracts at the dosage of 3 and 6 μg/ ml induced an accumulation of G0/G1 cells, as well as reduce in S and G2/M phases in MCF-7 and MDA-MB231 cells. Moreover, the aqueous and hydroalcoholic of U.maritima extracts at three concentrations [ 1.5, 3 and 6 μg/ ml ] in 24h inhibited the cell migration by 60% up to 70% respectively. In addition, the content of phenolic compounds in both extracts [aqueous and hydroalcoholic] was 7 mg and 10 mg gallic acid equivalent per gram of the crude extract, respectively. Conclusion: Our results suggest that U.maritima extracts has significant anti-cancer activity against breast cancer cells due to cell cycle arrest and induction of apoptosis pathway.

2018 ◽  
Vol Volume 11 ◽  
pp. 2409-2417 ◽  
Author(s):  
Longfei Yang ◽  
Huanran Liu ◽  
Min Long ◽  
Xi Wang ◽  
Fang Lin ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 92 ◽  
Author(s):  
Guan-Jun Yang ◽  
Chung-Nga Ko ◽  
Hai-Jing Zhong ◽  
Chung-Hang Leung ◽  
Dik-Lung Ma

Breast cancer is the one of the most frequent causes of female cancer mortality. KDM5A, a histone demethylase, can increase the proliferation, metastasis, and drug resistance of cancers, including breast cancer, and is thus an important therapeutic target. In the present work, we performed hierarchical virtual screening towards the KDM5A catalytic pocket from a chemical library containing 90,000 compounds. Using multiple biochemical methods, the cyclopenta[c]chromen derivative 1 was identified as the top candidate for KDM5A demethylase inhibitory activity. Compared with the well-known KDM5 inhibitor CPI-455 (18), 1 exhibited higher potency against KDM5A and much higher selectivity for KDM5A over both KDM4A and other KDM5 family members (KDM5B and KDM5C). Additionally, compound 1 repressed the proliferation of various KDM5A-overexpressing breast cancer cell lines. Mechanistically, 1 promoted accumulation of p16 and p27 by blocking KDM5A-mediated H3K4me3 demethylation, leading to cell cycle arrest and senescence. To date, compound 1 is the first cyclopenta[c]chromen-based KDM5A inhibitor reported, and may serve as a novel motif for developing more selective and efficacious pharmacological molecules targeting KDM5A. In addition, our research provides a possible anti-cancer mechanism of KDM5A inhibitors and highlights the feasibility and significance of KDM5A as a therapeutic target for KDM5A-overexpressing breast cancer.


2020 ◽  
Vol 5 (38) ◽  
pp. 11850-11853
Author(s):  
Anderson Roberto de Souza ◽  
Mona Stefany de Souza Castro ◽  
Thiago Olímpio de Souza ◽  
Rodrigo Cassio Sola Veneziani ◽  
Jairo Kenupp Bastos ◽  
...  

2019 ◽  
Vol 19 (15) ◽  
pp. 1874-1886
Author(s):  
Maria Schröder ◽  
Shazie Yusein-Myashkova ◽  
Maria Petrova ◽  
Georgi Dobrikov ◽  
Mariana Kamenova-Nacheva ◽  
...  

Background: Drug resistance is a major cause of cancer treatment failure. Most cancer therapies involve multiple agents, to overcome it. Compounds that exhibit strong anti-tumor effect without damaging normal cells are more and more in the focus of research. Chemotherapeutic drugs, combining different moieties and functional groups in one molecule, can modulate different regulatory pathways in the cell and thus reach the higher efficacy than the agents, which affect only one cellular process. Methods: We tested the effect of recently synthesized ferrocene-containing camphor sulfonamide DK-164 on two breast cancer and one breast non-cancer cell lines. The cytotoxic effects were evaluated using the standard MTT-dye reduction and clonogenic assays. The apoptotic or autophagic effects were evaluated by Annexin v binding or LC3 puncta formation assays respectively. Cell cycle arrest was determined using flow cytometry. Western blot and immunofluorescent analyses were used to estimate the localization and cellular distribution of key regulatory factors NFκB and p53. Results: Compound DK-164 has well pronounced cytotoxicity greater to cancer cells (MDA-MB-231 and MCF-7) compared to non-cancerous (MCF-10A). IC50 of the substance caused a cell cycle arrest in G1 phase and induced apoptosis up to 24 hours in both tumor cells, although being more pronounced in MCF-7, a functional p53 cell line. Treatment with IC50 concentration of the compound provoked autophagy in both tumor lines but is better pronounced in the more aggressive cancer line (MDA-MB-231). Conclusion: The tested compound DK-164 showed promising properties as a potential therapeutic agent.


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