Peptide SA12 inhibits proliferation of breast cancer cell lines MCF-7 and MDA-MB-231 through G0/G1 phase cell-cycle arrest

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.

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The Effect of a Ferrocene Containing Camphor Sulfonamide DK-164 on Breast Cancer Cell Lines

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190724094334 ◽

2019 ◽

Vol 19 (15) ◽

pp. 1874-1886

Author(s):

Maria Schröder ◽

Shazie Yusein-Myashkova ◽

Maria Petrova ◽

Georgi Dobrikov ◽

Mariana Kamenova-Nacheva ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Regulatory Pathways ◽

Cycle Arrest ◽

Mcf 7

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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The effects of licofelone, a dual lipoxygenase and cyclooxygenase inhibitor, with and without rosiglitazone in human MCF-7 and MDA-MB-231 breast cancer cells

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1537 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1537-1537 ◽

Cited By ~ 2

Author(s):

C. Kurkjian ◽

N. B. Janakiram ◽

S. Guruswamy ◽

C. V. Rao ◽

H. Ozer

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Combination Therapy ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Low Dose ◽

G1 Phase ◽

Cycle Arrest ◽

Dose Combination ◽

Mcf 7

1537 Background: Clinical and preclinical studies suggest that cyclooxygenase (COX)-2 inhibitors reduce the risk of various cancers, however, their administration is associated with an increased cardiovascular risk. Agents with 5-LOX/COX inhibition provide a possible approach for improving chemopreventive efficacy without unwanted side effects. COX and LOX inhibition have also been associated with an increase in PPAR γ expression. The present experiments tested the effects of licofelone (L) in breast cancer cell lines and assessed whether dual inhibition of LOX and COX may potentiate the action of rosiglitazone (R). Methods: MDA-MB-231 and MCF-7 cells were exposed to sub-toxic concentrations of L and R alone and in combination and analyzed for growth inhibition (MTT method), apoptosis (EB-AO and DAPI methods), cell-cycle analysis (flow cytometry), and protein expression (immunoblot method). Results: L and R inhibited cell growth in a dose-dependent manner in both cell lines. Combination therapy resulted in significant rates of apoptosis, particularly at high doses in both cell lines (p<0.001). Flow cytometric analysis showed that L and R exhibited cell cycle arrest at the G0/G1 phase in MDA-MB-231 cells. The low dose combination did not promote cell cycle arrest while the higher dose combination therapy demonstrated significant inhibition (p <0.0009). In MCF-7 cells, G0/G1 phase blockade was noted in L and R treated cells as well as in the low dose simultaneous combination therapy. Intermediate and high dose combination therapy exhibited increased cell cycle arrest at G0/G1 when L was administered 12 hours before R (p = 0.0030 and 0.0017). Western blot analysis showed increased expression of p21WAFI/CIPI and decreased cyclin D1 expression in both cell lines after therapy. Both agents induced caspase-3 expression in MDA-MB-231 cells at high concentrations, with even higher expression observed in the combination treatment. MCF-7 cells demonstrated PARP cleavage at all doses when compared to control. Conclusions: Our results suggest that L is a potential agent for prevention and treatment of breast cancer and the combination of low doses of L and R provide further promise in improving efficacy against breast cancer. No significant financial relationships to disclose.

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