Novel Butein Derivatives Repress DDX3 Expression by Inhibiting PI3K/AKT Signaling Pathway in MCF-7 and MDA-MB-231 Cell Lines

BackgroundBreast cancer is one of the major causes of mortalities noticed in women globally. DDX3 has emerged as a potent target for several cancers, including breast cancer to which currently there are no reported or approved drugs.MethodsTo find effective cancer therapeutics, three compounds were computationally designed tweaking the structure of natural compound butein. These compounds were synthesized and evaluated for their anticancer property in MCF-7 and MDA-MB-231 cell lines targeting DDX3. The in silico molecular docking studies have shown that the compounds have occupied the binding site of the human DDX3 target. Furthermore, to investigate the cell viability effect of 3a, 3b, and 3c on MCF-7 and MDA-MB-231 cell lines, the cell lines were treated with different concentrations of compounds for 24 and 48 h and measured using MTT assay.ResultsThe cell viability results showed that the have induced dose dependent suppression of DDX3 expression. Additionally, 3b and 3c have reduced the expression of DDX3 in MCF-7 and MDA-MD-231 cell lines. 3b or 3c treated cell lines increased apoptotic protein expression. Both the compounds have induced the apoptotic cell death by elevated levels of cleaved PARP and cleaved caspase 3 and repression of the anti-apoptosis protein BCL-xL. Additionally, they have demonstrated the G2/M phase cell cycle arrest in both the cell lines. Additionally, 3c decreased PI3K and AKT levels.ConclusionsOur results shed light on the anticancer ability of the designed compounds. These compounds can be employed as chemical spaces to design new prospective drug candidates. Additionally, our computational method can be adapted to design new chemical scaffolds as plausible inhibitors.

Download Full-text

Synthesis and Biological Evaluation of 1-(Diarylmethyl)-1H-1,2,4-triazoles and 1-(Diarylmethyl)-1H-imidazoles as a Novel Class of Anti-Mitotic Agent for Activity in Breast Cancer

Pharmaceuticals ◽

10.3390/ph14020169 ◽

2021 ◽

Vol 14 (2) ◽

pp. 169

Author(s):

Gloria Ana ◽

Patrick M. Kelly ◽

Azizah M. Malebari ◽

Sara Noorani ◽

Seema M. Nathwani ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Docking Studies ◽

Biological Evaluation ◽

Mitotic Catastrophe ◽

Phase Cell ◽

Computational Docking ◽

Er Positive ◽

Mcf 7

We report the synthesis and biochemical evaluation of compounds that are designed as hybrids of the microtubule targeting benzophenone phenstatin and the aromatase inhibitor letrozole. A preliminary screening in estrogen receptor (ER)-positive MCF-7 breast cancer cells identified 5-((2H-1,2,3-triazol-1-yl)(3,4,5-trimethoxyphenyl)methyl)-2-methoxyphenol 24 as a potent antiproliferative compound with an IC50 value of 52 nM in MCF-7 breast cancer cells (ER+/PR+) and 74 nM in triple-negative MDA-MB-231 breast cancer cells. The compounds demonstrated significant G2/M phase cell cycle arrest and induction of apoptosis in the MCF-7 cell line, inhibited tubulin polymerisation, and were selective for cancer cells when evaluated in non-tumorigenic MCF-10A breast cells. The immunofluorescence staining of MCF-7 cells confirmed that the compounds targeted tubulin and induced multinucleation, which is a recognised sign of mitotic catastrophe. Computational docking studies of compounds 19e, 21l, and 24 in the colchicine binding site of tubulin indicated potential binding conformations for the compounds. Compounds 19e and 21l were also shown to selectively inhibit aromatase. These compounds are promising candidates for development as antiproliferative, aromatase inhibitory, and microtubule-disrupting agents for breast cancer.

Download Full-text

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

OncoTargets and Therapy ◽

10.2147/ott.s154337 ◽

2018 ◽

Vol Volume 11 ◽

pp. 2409-2417 ◽

Cited By ~ 3

Author(s):

Longfei Yang ◽

Huanran Liu ◽

Min Long ◽

Xi Wang ◽

Fang Lin ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Breast Cancer Cell ◽

Phase Cell ◽

G1 Phase ◽

Breast Cancer Cell Lines ◽

Cycle Arrest ◽

Mcf 7

Download Full-text

Oxidized products ofα-linolenic acid negatively regulate cellular survival and motility of breast cancer cells

10.1101/517094 ◽

2019 ◽

Author(s):

Jorge L. Gutierrez-Pajares ◽

Celine Ben Hassen ◽

Camille Oger ◽

Jean-Marie Galano ◽

Thierry Durand ◽

...

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Linolenic Acid ◽

Cell Lines ◽

Cellular Adhesion ◽

Cellular Migration ◽

Breast Cancer Cell Lines ◽

Control Group ◽

Oxidized Products ◽

Mcf 7

AbstractBackgroundCancer is a major cause of death in the world, and more than six million new cases are reported every year. Despite recent advances in our understanding of the biological processes leading to the development and progression of cancer, there is still a need for new and effective agents to treat this disease. Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are non-enzymatically oxidized products of α-linolenic acid that are present in seeds and vegetable oils. They have been shown to possess anti-inflammatory and apoptosis-promoting activities in macrophages and leukemia cells, respectively.MethodsIn this work, seven PhytoPs (PP1-PP7) and one PhytoFs (PF1) were evaluated for their cytotoxic, chemosensitization and anti-migratory activities using the MCF-7 and MDA-MB-231 breast cancer cell lines.ResultsAmong the compounds tested, only three PhytoPs had a significant effect on cell viability compared to the control group:Ent-9-L1-PhytoP (PP6) decreased cell viability in both cell lines, while 16-F1t-PhytoP (PP1) and 9-L1-PhytoP (PP5) decreased viability in MCF-7 and MDA-MB-231 cells, respectively. When combined with a sub-cytotoxic dose of doxorubicin, these three PhytoPs significantly enhanced the cytotoxic effect on MCF-7 cells while the chemotherapeutic drug alone had no effect. In cellular motility assays,Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF could significantly inhibit cellular migration of MDA-MB-231 cells in a wound-healing and a transwell assays. In addition,Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF also enhanced cellular adhesion of MDA-MB-231 cells.ConclusionsThis study shows for the first time that the plant-derived compounds PhytoPs and PhytoFs could be further exploited alone or in combination with chemotherapy to improve the arsenal of therapies available against breast cancer.

Download Full-text

Synthesis and Antitumor Activity of Some N2-(Thien-3-yl)amidrazones

Zeitschrift für Naturforschung B ◽

10.5560/znb.2014-4062 ◽

2014 ◽

Vol 69 (7) ◽

pp. 811-816 ◽

Cited By ~ 3

Author(s):

Mohammed M. Abadleh ◽

Mustafa M. El-Abadelah ◽

Salim S. Sabri ◽

Hanan H. Mohammed ◽

Malek A. Zihlif ◽

...

Keyword(s):

Breast Cancer ◽

Antitumor Activity ◽

Cell Viability ◽

Cell Lines ◽

K562 Cell ◽

Cyclic Amine ◽

Cell Viability Assay ◽

Viability Assay ◽

A Cell ◽

Mcf 7

6aA set of new N2-(thien-3-yl)amidrazones (-h) incorporating N-piperazines and related congeners has been synthesized by reacting the hydrazonoyl chloride 4(derived from 3-aminothiophene- 2-carboxylate) with the appropriate sec-cyclic amine. The antitumor activity of these compounds was evaluated on breast cancer (MCF-7) and leukemic (K562) cell lines by a cell viability assay utilizing the tetrazolium dye (MTT). The amidrazone 6d encompassing the N-piperazine moiety, was the most active against MCF-7 and K562 with IC50 of 7.28 and 9:91 μM, respectively.

Download Full-text

Investigation of antioxidant activity and effect on cell viability of pyrrolidine compounds in MCF-7 (breast cancer) and DLD-1 (colon cancer) cell lines

International Journal of Biology and Chemistry ◽

10.26577/ijbch.2021.v14.i1.03 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Seda Mesci ◽

Melek Gül ◽

Tuba Yıldırım

Keyword(s):

Breast Cancer ◽

Colon Cancer ◽

Antioxidant Activity ◽

Cell Viability ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Colon Cancer Cell Lines ◽

Mcf 7

Download Full-text

The Dicyano Compound Induces Autophagic or Apoptotic Cell Death Via Twıst/C-Myc Axis Depending on Metastatic Characteristics of Breast Cancer Cells

10.21203/rs.3.rs-590805/v1 ◽

2021 ◽

Author(s):

Ozge ALVUR ◽

Hakan KUCUKSAYAN ◽

Yasemin BAYGU ◽

Nilgun KABAY ◽

Yasar GOK ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cell Lines ◽

Epithelial To Mesenchymal Transition ◽

Apoptotic Cell ◽

Treatment Strategies ◽

Breast Cancer Cell Lines ◽

Mesenchymal Transition ◽

Cancer Subtypes ◽

Mcf 7

Abstract Breast cancer is a heterogeneous disease which has distinct subtypes and therefore development of novel targeting treatments to fight aganist breast cancer is needed. Although autophagy and apoptosis considered as the major programmed cell death mechanisms are among the current target mechanisms, there are some difficulties in clinical treatment such as the development of drug resistance and cancer recurrence. Therefore it is important that illumination of distinctive mechanisms between cancer types for development novel treatment strategies. In this study, we examined the anti-proliferative effects of the triazole linked galactose substituted dicyano compound (hereafter referred to as the dicyano compound (the DC)) on two different breast cancer cell lines, MDA-MB-231 and MCF-7. We determined that response of each cell lines to the DC was different, since autophagy was induced in MDA-MB-231 and apoptosis was induced in MCF-7. For this reason, we hypothesized that these different responses may be due to the different characteristics of the cells and evaluated effects of aggresiveness degrees of both cell lines on response to the DC. As a result of our analysis, we determined that c-Myc regulation in both cell lines was different upon the DC treatment depending on expression of Twist, an epithelial-to-mesenchymal transition (EMT) mediator. Therefore, we suggest that Twist/c-Myc axis may have a role in different response to the DC-induced cell death pathways in breast cancer subtypes.

Download Full-text

Oxidized Products of α-Linolenic Acid Negatively Regulate Cellular Survival and Motility of Breast Cancer Cells

Biomolecules ◽

10.3390/biom10010050 ◽

2019 ◽

Vol 10 (1) ◽

pp. 50 ◽

Cited By ~ 1

Author(s):

Jorge L. Gutierrez-Pajares ◽

Celine Ben Hassen ◽

Camille Oger ◽

Jean-Marie Galano ◽

Thierry Durand ◽

...

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Linolenic Acid ◽

Cell Lines ◽

Cellular Adhesion ◽

Cellular Migration ◽

Breast Cancer Cell Lines ◽

Control Group ◽

Oxidized Products ◽

Mcf 7

Despite recent advances in our understanding of the biological processes leading to the development and progression of cancer, there is still a need for new and effective agents to treat this disease. Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are non-enzymatically oxidized products of α-linolenic acid that are present in seeds and vegetable oils. They have been shown to possess anti-inflammatory and apoptosis-promoting activities in macrophages and leukemia cells, respectively. In this work, seven PhytoPs (PP1–PP7) and one PhytoFs (PF1) were evaluated for their cytotoxic, chemosensitization, and anti-migratory activities using the MCF-7 and MDA-MB-231 breast cancer cell lines. Among the tested compounds, only three PhytoPs had a significant effect on cell viability compared to the control group: Ent-9-L1-PhytoP (PP6) decreased cell viability in both cell lines, while 16-F1t-PhytoP (PP1) and 9-L1-PhytoP (PP5) decreased viability of MCF-7 and MDA-MB-231 cells, respectively. When combined with a sub-cytotoxic dose of doxorubicin, these three PhytoPs displayed significantly enhanced cytotoxic effects on MCF-7 cells while the chemotherapeutic drug alone had no effect. In cellular motility assays, Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF could significantly inhibit cellular migration of MDA-MB-231 cells. In addition, Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF also enhanced cellular adhesion of MDA-MB-231 cells.

Download Full-text

Ricinus communis Butanol Fraction Inhibits MCF-7 Breast Cancer Cell Migration, Adhesion, and Invasiveness

Integrative Cancer Therapies ◽

10.1177/1534735420977684 ◽

2021 ◽

Vol 20 ◽

pp. 153473542097768

Author(s):

Rixile Mabasa ◽

Kholofelo Malemela ◽

Karabo Serala ◽

Mante Kgakishe ◽

Thabe Matsebatlela ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cell Migration ◽

Cell Viability ◽

Apoptotic Cell ◽

Ricinus Communis ◽

Gelatin Zymography ◽

Apoptotic Cell Death ◽

Butanol Fraction ◽

Mcf 7

In this study, the potential of an n-butanol fraction from Ricinus communis to prevent metastasis in MCF-7 breast cancer cells was investigated. The effect of the fraction on BUD-8 and MCF-7 cell viability was assessed using the MTT assay. Apoptotic cell death was analyzed by Hoechst staining assay. The antimetastatic effect of the fraction on MCF-7 cell was evaluated using the wound healing, adhesion and Boyden chamber invasion assays. Gelatin-zymography was used to assess the effect of the fraction on MMP-2 and MMP-9 activity. The expression profile of proteins implicated in metastasis and angiogenesis was determined using the human angiogenesis antibody array kit, following treatment with the fraction. BUD-8 cell viability was significantly reduced at concentrations between 300 and 500 µg/ml of the extract. In contrast, a significant reduction in cell viability was seen in MCF-7 cells treated with 400 to 500 µg/ml of the fraction. At sub-lethal concentrations (100 and 200 µg/ml) of the fraction, no nuclei morphological changes associated with apoptotic cell death were observed in MCF-7 cells. In addition, the fraction showed to have an inhibitory effect on MCF-7 cell migration, adhesion, invasiveness, and MMP-2 activity. Moreover, the fraction was seen to modulate the expression of several proteins, such as MMP-9, uPA, VEGF, and TGF-β1, playing a role in the metastasis process. This study demonstrates that the n-butanol fraction of R. communis can inhibit major steps of the metastatic cascade and modulate metastasis regulatory proteins. Thus, the fraction can be considered a potential source of antimetastatic agents that could be useful in the treatment of malignant cancers.

Download Full-text

INSILICO DESIGN, SYNTHESIS AND CHARACTERIZATION OF SOME NOVEL BENZOTHIAZOLE DERIVATIVES AS ANTI-CANCER AGENTS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i4.16407 ◽

2017 ◽

Vol 10 (4) ◽

pp. 150

Author(s):

Leena K Pappachen ◽

Subin Mary Zachariah ◽

Deepthy Chandran

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Docking Studies ◽

Design Synthesis ◽

Standard Drug ◽

Mass Spectral ◽

Benzothiazole Derivatives ◽

Anti Cancer ◽

Mcf 7

Objectives: Cancer is a disease characterized by uncontrollable, irreversible, independent, autonomous, uncoordinated and relatively unlimited and abnormal over growth of tissues. Breast cancer is the second most common type of cancer after lung cancer. The aim of the study is to carry out the docking studies, synthesis and anti-tumour activities of Benzothiazole derivatives containing oxadiazole groups or amino groups.Methods: The docking studies of benzothiazole derivatives were done with known anti-cancer targets like oestrogen receptor by using argus lab and auto dock programmes with the standard drug tamoxifen. Based upon the results obtained from the molecular modeling, the derivatives were selected for the synthesis. The synthesized compounds were characterized by melting point, TLC, IR, 1H NMR, 13CNMR, MASS spectral data and screened for their in- vitro anti-cancer activities.Results: The docking scores obtained for benzothiazole derivatives (BT1,BT2,BT3,BT4) and std.tamoxifen from the preliminary docking program by using argusLab were- 9.68,-9.4,-9.59, -11.1988,-9.71 and by using autodock program were -6.29, -5.25,-7.19,-7.48,-3.86 respectively. All the four derivatives were synthesized, characterized and subjected to in vitro anticancer screening by MTT assay in breast cancer (MCF-7) cell lines. Compounds DBT1, DBT2, DBT3 were the most active compounds against MCF-7 cell lines with IC50 of 70.0, 64.0 and 65.0, respectively.Conclusion: All the four derivatives show good docking scores when compared to standard drug and can be concluded that all the synthesized benzothiazole ligands show good anti-cancer property.Keywords: Benzothiazole, Oxadiazole, Estrogen receptor, Anticancer targets.

Download Full-text