scholarly journals MiR-195 regulates mitochondrial function by targeting mitofusin-2 in breast cancer cells

2018 ◽  
Author(s):  
Paresh Kumar Purohit ◽  
Ruairidh Edwards ◽  
Kostas Tokatlidis ◽  
Neeru Saini
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Mitochondrial Function ◽  
Breast Cancer Cells ◽  
Therapeutic Potential ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Mitofusin 2 ◽  
Er Positive ◽  
And Function

AbstractMitochondrial dynamics is a highly dysregulated process in cancer. Apoptosis and mitochondrial fission are two concurrent events wherein increased mitochondrial fragmentation serves as a hallmark of apoptosis. We have shown earlier that miR-195 exerts pro-apoptotic effects in breast cancer cells. Herein, we have demonstrated miR-195 as a modulator of mitochondrial dynamics and function. Imaging experiments upon miR-195 treatment have shown that mitochondria undergo extensive fission. We validated mitofusin2 as a potential target of miR-195. Which may provide a molecular explanation for the respiratory defects induced by miR-195 over-expression in breast cancer cells? Active, but not total, mitochondrial mass, was reduced with increasing levels of miR-195. We have further shown that miR-195 enhances mitochondrial SOD-2 expression but does not affect PINK1 levels in breast cancer cells. Collectively, we have revealed that miR-195 is a modulator of mitochondrial dynamics by targeting MFN2 thereby impairing mitochondrial function. Concomitantly, it enhances the scavenger of reactive oxygen species (SOD-2) to maintain moderate levels of oxidative stress. Our findings suggest a therapeutic potential of miR-195 in both ER-positive as well as ER-negative breast cancer cells.

scholarly journals MiR-195 regulates mitochondrial function by targeting mitofusin-2 in breast cancer cells

RNA Biology ◽  
2019 ◽  
Vol 16 (7) ◽  
pp. 918-929 ◽  
Author(s):  
Paresh Kumar Purohit ◽  
Ruairidh Edwards ◽  
Kostas Tokatlidis ◽  
Neeru Saini
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Mitochondrial Function ◽  
Breast Cancer Cells ◽  
Mitofusin 2

In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone

2021 ◽  
pp. 096032712199945
Author(s):  
AT Aliyev ◽  
S Ozcan-Sezer ◽  
A Akdemir ◽  
H Gurer-Orhan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effects ◽  
Antiestrogenic Activity ◽  
Er Positive ◽  
In Vivo Effects ◽  
Mcf 7

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

scholarly journals 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

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.

Molecular identification of ER?-positive breast cancer cells by the expression profile of an intrinsic set of estrogen regulated genes

2004 ◽  
Vol 200 (3) ◽  
pp. 440-450 ◽  
Author(s):  
Alessandro Weisz ◽  
Walter Basile ◽  
Claudio Scafoglio ◽  
Lucia Altucci ◽  
Francesco Bresciani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Expression Profile ◽  
Molecular Identification ◽  
Breast Cancer Cells ◽  
Er Positive ◽  
Positive Breast Cancer

Potential of bacterial culture media in biofabrication of metal nanoparticles and the therapeutic potential of the as-synthesized nanoparticles in conjunction with artemisinin against MDA-MB-231 breast cancer cells

2018 ◽  
Vol 234 (5) ◽  
pp. 6951-6964 ◽  
Author(s):  
Badrealam Farheen Khan ◽  
Hamidullah ◽  
Sonam Dwivedi ◽  
Rituraj Konwar ◽  
Swaleha Zubair ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metal Nanoparticles ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Bacterial Culture ◽  
Therapeutic Potential ◽  
Culture Media

scholarly journals Overexpression of BQ323636.1 Modulated AR/IL-8/CXCR1 Axis to Confer Tamoxifen Resistance in ER-Positive Breast Cancer

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Ho Tsoi ◽  
Ling Shi ◽  
Man-Hong Leung ◽  
Ellen P. S. Man ◽  
Zi-Qing So ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tamoxifen Resistance ◽  
In Silico Analysis ◽  
Luciferase Reporter ◽  
Androgen Response Element ◽  
Er Positive

NCOR2 is a co-repressor for estrogen receptor (ER) and androgen receptor (AR). Our group previously identified a novel splice variant of NCOR2, BQ323636.1 (BQ), that mediates tamoxifen resistance via interference of NCOR2 repression on ER. Luciferase reporter assay showed BQ overexpression could enhance the transcriptional activity of androgen response element (ARE). We proposed that BQ employs both AR and ER to confer tamoxifen resistance. Through in silico analysis, we identified interleukin-8 (IL-8) as the sole ERE and ARE containing gene responsiveness to ER and AR activation. We confirmed that BQ overexpression enhanced the expression of IL-8 in ER+ve breast cancer cells, and AR inhibition reduced IL-8 expression in the BQ overexpressing cell lines, suggesting that AR was involved in the modulation of IL-8 expression by BQ. Moreover, we demonstrated that IL-8 could activate both AKT and ERK1/2 via CXCR1 to confer tamoxifen resistance. Targeting CXCR1/2 by a small inhibitor repertaxin reversed tamoxifen resistance of BQ overexpressing breast cancer cells in vitro and in vivo. In conclusion, BQ overexpression in ER+ve breast cancer can enhance IL-8 mediated signaling to modulate tamoxifen resistance. Targeting IL-8 signaling is a promising approach to overcome tamoxifen resistance in ER+ve breast cancer.

scholarly journals Elaborating the Mechanism of Cell Killing of a Novel Chemotheraputic Drug Targeting Breast Cancer

2019 ◽  
Vol 4 ◽  
Author(s):  
Phat Do
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Unique Feature ◽  
Cell Killing ◽  
Tamoxifen Treatment ◽  
Length Variation ◽  
Er Positive ◽  
New Diagnosis ◽  
Dependent Pathway

Breast cancer (BC) is the second most commonly diagnosed cancer in women in the world. In 2018, there were more than 2 million new diagnosis. It is estimated that1 in 8 women will develop invasive breast cancer over the course of her lifetime. Traditional treatments of BC include surgery, radiation, and chemotherapy therapy; however, these treatments are non-specific and potentially kill peripheral, healthy cells. More specific treatments are needed, most notably to target a unique feature of the cancer cells. Interestingly, 70% of BC cells upregulate estradiol-dependent pathway, a characteristic essential for rapid cell growth. Current BC drugs, such as Tamoxifen, Faslodex, or Femarahave targeted this pathway to preferentially kill BC cells. However, the problems with these drugs are two-fold. (1) Drugs produce considerable side effects. For example, Femera causes considerable musculoskeletal failures. Tamoxifen is also shown to produce secondary cancer growth, such as endometrial cancer. (2) Breast cancer cells resist drugs very quickly. For instance, one third of women who are treated with Tamoxifen for five years relapse within fifteen years. The resulting tumor then become resistant to Tamoxifen treatment. For these two reasons, there is a need for new chemotherapeutic drugs. Our research group studies a novel estrogen-receptor targeting drug: Estradiol-R-Melex. This compound has the estradiol molecule linked to a DNA alkylating agent, Melex. We connected the two moieties using a linker consisting of various lengths, i.e., one, two, and three methyl groups. The linker length variation is to optimize the cell killing property of our small drug molecule. We hypothesize that Est-n-Melex enters the ER positive cancer cells more rapidly than ER-normal cells.

scholarly journals HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol

2020 ◽  
Vol 11 ◽  
Author(s):  
Imran Hussain ◽  
Paromita Deb ◽  
Avisankar Chini ◽  
Monira Obaid ◽  
Arunoday Bhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Female Rats ◽  
Er Positive ◽  
Gene Regulatory ◽  
Cancer Tissues ◽  
Positive Breast Cancer

HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cells in vitro. HOXA5 expression is also upregulated in vivo in the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERβ downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.

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