214 TRICLOSAN-INDUCED CELL CYCLE RELATED AND APOPTOTIC RELATED GENES WERE REVERSED BY KAEMPFEROL IN IN VITRO BREAST CANCER AND XENOGRATED MOUSE MODELS

2015 ◽  
Vol 27 (1) ◽  
pp. 197
Author(s):  
S.-H. Kim ◽  
K.-C. Choi
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cell Viability ◽  
Breast Cancer Cells ◽  
Cyclin E ◽  
Negative Control ◽  
Cyclin D ◽  
Mcf 7

Triclosan (Tri) is one of many endocrine-disrupting chemicals (EDCs) that are scattered with environment agents, such as toothpastes, deodorants, and cleaning supplies. As a phytoestrogen, kaempferol (Kae) is one of bioflavonoids, which has been found in a variety of vegetables including broccoli, tea, and tomatoes. Although Kae may have anti-cancer activity, its exact mechanism is under investigation, and might be the induction of apoptosis and inhibition of cell proliferation or angiogenesis. In this study, we examined the anti-proliferative effects of Kae in Tri-induced cell growth in MCF-7 breast cancer cells. A proper concentration and co-treatment effect of Tri and Kae were determined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay to measure cell viability in vitro. MCF-7 cells were cultured with a negative control (0.1% DMSO), E2 (1 × 10–9 M), Tri (10–5–10–8 M) and Kae (50, 70, and 90 mM). In this study, treatment with Tri (10–6 M) increased the cell viability of MCF-7 cells, while Kae (50 mM) significantly reduced the cell viability compared to the negative control (P < 0.05). In addition, Kae significantly reversed Tri-induced MCF-7 cell growth at 50 mM compared with a higher concentration (100 mM; P < 0.05). To confirm that Kae inhibited Tri-induced cell growth, we examined the transcriptional levels of cell growth and apoptosis-related markers, i.e. cyclin D, p21, cyclin E, p27 and bcl-2, and bax genes, using reverse transcription (RT)-PCR. The expression levels of cyclin D, cyclin E, and bax/bcl-2 ratio were increased, while those of p21 and p27 mRNAs were decreased by Tri in MCF-7 cells. In addition, Kae treatment significantly reversed Tri-induced gene expressions in an opposite manner. In parallel with its mRNA level, the protein level of cyclin E, p-ERK and p-MEK1/2 were induced by Tri while it was reversed by Kae as shown by Western blot analysis. The expression levels of p21 and bax genes were altered by Tri and reversed by Kae treatment in this study. As an in vivo model, a xenografted mouse model was generated following injection with MCF-7 breast cancer cells in 6 weeks. In parallel with in vitro results, tumour volumes following treatment with E2 and Tri were continually increased compared to a vehicle (corn oil). It was of interest that treatment of the mice with combination of E2 plus Kae or Tri plus Kae showed less tumour formation rather than that of singly treated mice with E2 or Tri. Taken together, these results indicate that Kae may inhibit the growth of MCF-7 cells via regulating of cell cycle and apoptosis-related genes. In addition, EDC-induced progression of breast cancer may be suppressed by a phytoestrogen, i.e. Kae, in a specific manner.

scholarly journals Effects of suramin on cell-cycle kinetics of MCF-7 human breast cancer cells in vitro

1993 ◽  
Vol 67 (2) ◽  
pp. 232-236 ◽  
Author(s):  
JA Foekens ◽  
AM Sieuwerts ◽  
EMJ Stuurman-Smeets ◽  
HA Peters ◽  
JGM Klijn
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Cell Cycle Kinetics ◽  
Kinetics Of ◽  
Mcf 7

Synthesis, Characterization, Molecular Docking, In Vitro Biological Evaluation and In Vitro Cytotoxicity Study of Novel Thiazolidine-4-One Derivatives as Anti-Breast Cancer Agents‏‏

2021 ◽  
Vol 21 ◽  
Author(s):  
Zainab Y. Kadhim ◽  
Hasanain G.J. Alqaraghuli ◽  
Muna Tawfeeq Abd
Keyword(s):  
Breast Cancer ◽  
Antibacterial Activity ◽  
Molecular Docking ◽  
Cell Growth ◽  
Breast Cancer Cells ◽  
Docking Study ◽  
In Vitro Cytotoxicity ◽  
T1 And T2 ◽  
Mcf 7

Background: Thiazolidine-4-one is a promising class of heterocyclic compounds with interesting pharmacological and biological activities, such as anticancer and antibacterial. Therefore, many researchers have synthesized thiazolidine-4-ones and evaluated their biological potential for developing new drugs. Objective: In this study, two novel thiazolidine-4-one derivatives (T1 and T2) were synthesized and evaluated for their antibacterial activity toward Staphylococcus aureus, Escherichia coli and Proteus mirabilis. Also, the cytotoxic activities of compounds T1 and T2 were estimated against MCF-7 (HER2+, ER+ and ER+) and MDA-MB-231 (triple-negative) human breast cancer cell lines. The chemical structure of compounds T1 and T2 was proven using spectral techniques (FT-IR, 1HNMR, and 13C-NMR) and CHN elemental analysis. Methods: The synthesis of thiazolidine-4-one compounds was performed in two steps. The first step consisted of the formation of Schiff bases S1 and S2. In the second step, the synthesized Schiff bases were reacted with thioglycolic acid to prepared thiazolidine-4-one compounds T1 and T2. Hemolysis assay, molecular docking, cytotoxicity activity (MTT assay) and antibacterial activity (disc diffusion assay) were studied. Results: The hemolysis study demonstrated that the hemolytic ratio of compounds T1 and T2 at (1, 2 and 3) mg/ml was less than 4%. MTT assay showed that 100 µg/ml of compounds T1 and T2 diminish the MCF-7 cell growth up to 80.05 ± 1.72 and 69.85 ± 3.26 respectively after 72 hrs, while the same concentration of compounds T1 and T2 reduces the MDA-MB-231 cell growth up 70.28 ± 2.31 and 57.15 ± 1.49, respectively. The inhibition zone of compounds T1 and T2 were 12 mm at 50 mg/ml and 10 mm at 5 mg/ml in E. coli bacteria. Furthermore, a docking study was carried out to investigate the affinity and binding mode of compounds T1 and T2 towards the ERα, VEGF, and HER2 protein receptors in breast cancer cells. Data obtained from the docking study were exactly identical to that obtained from in vitro cytotoxicity assay. Conclusion: The results proved that compound T1 is an optimal anticancer agent toward breast cancer cells and the hemolysis study indicates the use of safety inside the body for compound T1. Synthesized compound T1 was most effective against MCF-7 cells compared to MDA-MB-231 cells and more effective than the reference drug tamoxifen in breast cell lines. The high cytotoxicity of compound T1 on the growth of MCF‐7 cells because T1 binds with a high degree of affinity to the estrogen and HER2 receptors, which in turn inhibits cell proliferation and induces apoptosis.

In Vitro Assessment of Homeopathic Potencies of Hydrastis canadensis on Hormone-Dependent and Independent Breast Cancer

Homeopathy ◽  
2020 ◽  
Vol 109 (04) ◽  
pp. 198-206
Author(s):  
Sabiha Khan ◽  
Debadatta Nayak ◽  
Anil Khurana ◽  
Raj Kumar Manchanda ◽  
Chanderdeep Tandon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Caspase 3 ◽  
Hydrastis Canadensis ◽  
Induction Of Apoptosis ◽  
Mcf 7

Abstract Background Breast cancer is the second leading cause of cancer-related deaths in women. Conventional treatment such as chemotherapy, hormonal therapy and radiotherapy has decreased the mortality rate among cancer patients but has also revealed long-term side effects. Drug resistance and toxicity to normal cells compound the problems associated with the use of modern medicines. Hence, complementary or alternative treatment options are being explored. The current study, using different homeopathic potencies of Hydrastis canadensis, was conducted to distinguish between any effects they might have on hormone-dependent and independent breast cancer. Materials and Methods The cytotoxic effect of homeopathic medicine Hydrastis on hormone-dependent (MCF 7) and hormone-independent (MDA-MB-468) breast cancer cells was assessed using viability and colony-forming assays after 48 or 72 hours of treatment. Flow cytometry-based Annexin V-PI (propidium iodide), caspase 3 and cell cycle analysis was performed following treatment of cells with mother tincture or various potencies of Hydrastis (1C, 2C, 30C, 200C). Results Different potencies of Hydrastis displayed selective cytotoxic effects against MCF 7 cells, but only marginal effects against MDA-MB-468. The maximum cytotoxicity was established in the case of 1C following 72 hours of treatment. Treatment of breast cancer cells revealed an increase in the G0/G1 cell population, along with an increase in the caspase 3 levels and induction of apoptosis. Conclusion Hydrastis may have a selective cytotoxic effect against hormone-dependent breast cancer MCF 7 cells, leading to cell cycle arrest in the G0/G1 phase, which could be the plausible reason for the induction of apoptosis. The results need to be validated in vivo.

scholarly journals Ursolic Acid Enhances Doxorubicin Cytotoxicity on MCF-7 Cells Mediated by G2/M Arrest

2012 ◽  
Vol 3 (3) ◽  
pp. 410
Author(s):  
Ibrahim Arifin ◽  
Adam Hermawan ◽  
Muthi' Ikawati ◽  
Sari Haryanti ◽  
Anindyajati Anindyajati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agent ◽  
Ic50 Value ◽  
Combinational Treatment ◽  
Mcf 7

Ursolic acid has been widely known to possess biological activity against numerous tumor cell lines. Previous studies revealed its cytotoxicity on several cancer cells in vitro by either inducing apoptosis or cell cycle modulation. This study was conducted to investigate ursolic acid’s cytotoxicity solely and in combination with a chemotherapeutic agent, doxorubicin, on MCF-7 breast cancer cells, followed by observation on its mechanism. Cytotoxicity of single and combinational treatment of ursolic acid and doxorubicin on MCF-7 breast cancer cells were conducted by using MTT assay. Single treatment was then evaluated by determining IC50 value, while combinational treatment was evaluated by analyzing cell viability and evaluating combination index (CI). To explore the mechanism underlying cytotoxic effect on respected cells, further analysis on cell cycle profile of single and combinational treatment was conducted by flow cytometry. Twenty four hours treatment of ursolic acid inhibited MCF-7 cells’ growth with IC50 value of 37 µM, while combinational treatment showed that several concentration combinations of ursolic acid and doxorubicin exhibited synergism of cytotoxic activity on MCF-7 cells, giving optimum CI value of 0.54. Flow cytometric analysis showed that combinational treatment induced G2/M arrest in MCF-7 cells. These results show that ursolic acid is promising to be developed as either single chemopreventive agent, or as doxorubicin’s co-chemotherapeutic agent in breast cancer treatment. Observation on the selectivity as part of safety aspect together with in silico, in vitro, and in vivo study on its molecular mechanism should be conducted.Keywords: ursolic acid, doxorubicin,co-chemotherapeutic agent, breast cancer, cell cycle

scholarly journals Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via Integrating ERK/JNK Pathway

2020 ◽  
Author(s):  
Jianghong Cheng ◽  
Mingli Li ◽  
Chi-Meng Tzeng ◽  
Xingchun Gou ◽  
Shuai Chen
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Viability ◽  
Cancer Cells ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Suppressor Gene ◽  
Pathological Stages ◽  
Mcf 7

Abstract Background: Suppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells. However, there is no report of ST5 expression or function in the progression of breast cancer.Methods: ST5 expression in different subtypes and pathological stages of breast cancer was determined by Oncomine database, Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.4) analysis and immunohistochemistry. Cell viability was measured by CCK8 assay and metastatic behavior was assessed using scratch wound model and Transwell. Flow cytometry was employed for cell cycle and apoptosis detection, and methylation-specific PCR (MSP) was used to detect methylation level.Results: ST5 was expressed at low level in different subtypes of breast cancer specimens compared to normal breast and there was a negative association between ST5 status and pathological stages of breast cancer patients. Additionally, ST5 was lower in cases of recurrent and invasive breast cancer than that in non-recurrent and non-invasive patients. In in vitro experiment, ST5 status was also negatively associated with the invasive capability of breast cancer cells, showing lower in MDA-MB-231 and SKBR3 cell lines than that in MCF-7 cells. ST5-downregulation promoted, while ST5-upregulation inhibited the tumour characteristics of MDA-MB-231 cells including cell viability, cell cycle and migration. And exogenous ST5 also elevated, but ST5 depletion limited the proportion of apoptotic cells in MDA-MB-231 cells. However, the alteration of ST5, no matter upregulation or downregulation, had no impact on tumour behaviors of MCF-7 cells. Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated JNK and ERK1/2, and subsequently the expression of c-Myc. Of note, low level of ST5 in breast cancer cells was possibly related with the aberrant methylation of ST5 promoter region.Conclusion: Our findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment.

223 PROGRESSION OF BREAST CANCER WAS CAUSED BY TREATMENT WITH BENZOPHENONE-1 AND NONYL-PHENOL VIA ALTERATION OF CELL CYCLE AND METASTASIS-RELATED GENES IN A CELLULAR MODEL

2015 ◽  
Vol 27 (1) ◽  
pp. 201
Author(s):  
S.-J. In ◽  
K.-A. Hwang ◽  
S.-H. Kim ◽  
K.-C. Choi
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cathepsin D ◽  
Breast Cancer Cells ◽  
Negative Control ◽  
Signalling Pathway ◽  
Mcf 7

Endocrine disrupting chemicals (EDC) are defined as environmental compounds that may result in adverse health problems such as cancer proliferaition and metastasis in humans. Benzophenone-1 (2,4-dihydroxybenzophenone, BP-1) and nonyl-phenol (NP) are known as typical EDCs. They are discharged from numerous industrial products including plastics, pesticides, drugs, detergents, and cosmetics. In this study, we examined the effect of BP-1 and NP on the growth of MCF-7 human breast cancer cells expressing oestrogen receptors (ER) in comparison with E2 to assess their risk in cancer progression. In cell viability assay, BP-1 (10–5, 10–6, and 10–7 M) and NP (10–6 and 10–7 M) were determined to induce the proliferation of MCF-7 cells as well as E2 (10–9 M) was compared to a negative control treated with DMSO (P < 0.05). Next, to confirm that BP-1 and NP increase growth and metastasis of MCF-7 cells, the alterations in transcriptional and translational levels of related markers, i.e. cyclin D1, p21, and cathepsin D, were examined by reverse-transcription (RT)-PCR and Western blot assay. Cyclin D1 is a factor responsible for G1/S cell cycle transition and p21 is a potent cyclin-dependent kinase (CDK) inhibitor that arrests cell cycle in G1 phase. Cathepsin D is one of the proteases that are responsible for cancer progression and metastasis. Treatment of MCF-7 breast cancer cells with BP-1 (10–5 M) or NP (10–6 M) resulted in up-regulation of cyclin D1 and cathepsin D and down-regulation of p21 at transcriptional and translational levels as well as E2 (10–9 M) compared to a negative control treated with DMSO (P < 0.05). In addition, E2, BP-1, or NP-induced alterations of these genes were reversed by the presence of ICI 182 780 (10–8 M), an ER antagonist, suggesting that the changes in these gene expressions may be regulated by ER-dependent signalling pathway. In conclusion, these results suggest that BP-1 and NP, like E2, may accelerate the growth of MCF-7 breast cancer cells by regulating cell-cycle-related genes through ER-mediated signalling pathway. Furthermore, these EDCs can adversely affect human health by promoting cancer metastasis through the amplification of cathepsin D via ER-dependent signalling pathway.

scholarly journals Induction of Apoptosis and Regulation of MicroRNA Expression by (2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) Treatment on MCF-7 Breast Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1277
Author(s):  
Swee Keong Yeap ◽  
Norlaily Mohd Ali ◽  
Muhammad Nadeem Akhtar ◽  
Nursyamirah Abd Razak ◽  
Zhi Xiong Chong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
M Cell ◽  
Cytotoxic Effects ◽  
Er Positive ◽  
Mcf 7

(2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) is a synthetic curcumin analogue, which has been reported to possess anti-tumor, anti-metastatic, and anti-invasion properties on estrogen receptor (ER) negative breast cancer cells in vitro and in vivo. However, the cytotoxic effects of BHMC on ER positive breast cancer cells were not widely reported. This study was aimed to investigate the cytotoxic potential of BHMC on MCF-7 cells using cell viability, cell cycle, and apoptotic assays. Besides, microarray and quantitative polymerase chain reaction (qPCR) were performed to identify the list of miRNAs and genes, which could be dysregulated following BHMC treatment. The current study discovered that BHMC exhibits selective cytotoxic effects on ER positive MCF-7 cells as compared to ER negative MDA-MB-231 cells and normal breast cells, MCF-10A. BHMC was shown to promote G2/M cell cycle arrest and apoptosis in MCF-7 cells. Microarray and qPCR analysis demonstrated that BHMC treatment would upregulate several miRNAs like miR-3195 and miR-30a-3p and downregulate miRNAs such as miR-6813-5p and miR-6132 in MCF-7 cells. Besides, BHMC administration was also found to downregulate few tumor-promoting genes like VEGF and SNAIL in MCF-7. In conclusion, BHMC induced apoptosis in the MCF-7 cells by altering the expressions of apoptotic-regulating miRNAs and associated genes.

IN-VITRO AND IN-VIVO STUDIES OF THE POSSIBLE CHEMOPREVENTIVE FUNCTIONS OF SOYBEAN ISOFLAVONE AND FLAVONOIDS ON BREAST CANCER

2019 ◽  
Vol 31 (06) ◽  
pp. 1950045
Author(s):  
Shoei-Loong Lin ◽  
Ming-Tse Lin ◽  
Mei-Yan Chen ◽  
Ting-Kai Leung
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
In Vivo Experiment ◽  
Mcf 7

Objectives: In this study, we assess the possible influence of soybean isoflavone (genistein) and other flavonoids (quercetin and catechin) on breast cancer chemoprevention. We design in-vitro and in-vivo experiments to analyze the effect of genistein, quercetin and catechin on cell proliferation, cell migration, and angiogenesis of breast cancer cells. Methods: In cell proliferation experiment, MCF-7 cells, SKBR-3 cells, and HUVEC cells were treated with genistein and other flavonoids (catechin and/or quercetin) for 48[Formula: see text]h to assess the influence on cell growth of normal and breast cancer cells. In cell motility test, we analyze the effect of isoflavone and flavonoids on migration ability of MCF-7 cells by 16[Formula: see text]h and SKBR-3 cells by 24[Formula: see text]h in two different concentrations (1.25[Formula: see text][Formula: see text]g/ml and 2.5[Formula: see text][Formula: see text]g/ml). In the in-vivo experiment, SKBR-3 cells mixed with PBS and catechin, respectively, were injected subcutaneously into nude mice, then we investigated the effect of catechin on cell growth by observing subcutaneous tumor size changes after 15 days. Results: The results suggest that genistein and quercetin can significantly inhibit proliferation of breast cancer cells, and their inhibitory effects are independent of estrogen receptor. In cell motility tests, all of the three phytochemicals were effective in the inhibition of cell migration on two breast cancer cell lines, except for quercetin on cell migration of SKBR-3 cell line. In the in-vitro experiment, catechin showed stimulatory effect on cell proliferation of HUVEC cell line, which may consider positive effect on angiogenesis, rather than inhibitory effect. However, in the in-vivo experiment, it showed no significant change in tumor size between the groups of with and without catechin treatment. Conclusions: According to our study, the results suggest that isoflavone and flavonoids tend to inhibit cell growth and metastasis of breast cancer cells. Our in-vivo experiment does not reach a significant result, and it may be due to lower catechin concentration. Under in-vivo environment, we should also consider the possible metabolic forms of catechin that cause different result from the in-vitro study.

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