Increased proliferation/aggressiveness and metastatic potential of therapy targeted surviving breast adenocarcinoma cells as well as bystander non-targeted cancer cells; role of therapy-induced iNOS/NO, and beneficial effects of iNOS inhibitors

Loss of or lowered retinoblastoma (Rb) expression has been included as a prognostic indicator in breast cancer. Low or no Rb expression is seen most commonly in high-grade breast adenocarcinomas, suggesting that a relationship may exist between loss of Rb and a less differentiated state, high proliferation rate, and high metastatic potential. In this study, we compared Rb function in two established breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231, and in an established immortalized mammary epithelial cell line, MCF10A. Cells were synchronized in G0/G1 and were released for several durations, at which time total Rb protein, mRNA, and Rb/E2F/DNA complex formation were evaluated. Rb protein was significantly higher in the tumor cells than in MCF10A cells. However, Rb function was high for a longer duration in MCF10A cells as compared with MCF-7 and MDA-MB-231 cells. Our data support the general conclusion that Rb function, but not necessarily Rb protein, is lower in highly malignant breast adenocarcinoma cells as compared with lower grade tumor cells. These results emphasize the relevance of assessing Rb function over Rb protein. This is particularly important if Rb is to be used as a prognostic indicator for breast adenocarcinoma.

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An Investigation on Cytotoxicity Effect of Putrescine-Sulphur Analogues on Breast Cancer (Mcf-7), Human Lung Adenocarcinoma (A549) and Colorectal Cancer (Hct-8) Cell Lines

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v16i1.1135 ◽

2017 ◽

Vol 16 (1) ◽

Author(s):

Norsuhana Halim ◽

Radiah Abdul Ghani ◽

Adzly Hairee Sahabudin ◽

Fiona How Ni Fong

Keyword(s):

Lung Adenocarcinoma ◽

Cancer Cells ◽

Cell Lines ◽

Human Lung ◽

Breast Adenocarcinoma ◽

Normal Cells ◽

Human Lung Adenocarcinoma ◽

Adenocarcinoma Cells ◽

Specific Cancer ◽

Mcf 7

Introduction: Cancer is one of the global health problems that has a detrimental effect to a person's life. However, chemotherapeutic agents success are subject to the side effects due to lack of specificity in the drug delivery system to cancer cells and an increase risk of systemic toxicity to the normal cells. Polyamine transport system (PTS) is one of the potential pathways for transporting anticancer agent into specific cancer cells. This is due to the upregulation of PTS in cancer cells compared to normal cells for the proliferation activity. The aim of this study was to investigate the cytotoxicity effect of putrescine-sulphur analogues type 1 (PSA-1) and type 2 (PSA-2) on human lung adenocarcinoma cells (A549), human colorectal adenocarcinoma cells (HCT-8) and human breast adenocarcinoma cell (MCF-7). Materials and method: The cytotoxicity effect of newly synthesized PSA-1 and PSA-2 were evaluated on selected cancer cells; MCF-7, A549 and HCT-8 cell lines. The halfmaximal inhibitory concentration (IC50) obtained from tetrazolium bromide (MTT) assay was derived from the dose-response graph for all cell lines. Results: PSA-2 elicited cytotoxicity effect, eventhough the IC50 values were not potent with IC50 of 5.4 mM, 5.2 mM and 7.0 mM for MCF-7/48h, A549/48h and HCT-8/48h, respectively. The PSA-1 compound exhibited cytotoxicity effect in all cell lines, however, the compound failed to induce anti-proliferation at the concentration of 3 mM and above. The cytotoxicity of PSA-2 compound against MCF-7 cell lines showed higher potency compared to A549 and HCT-8 cell lines. Conclusion: It was suggested that PSA-2 compound was able to exert cytotoxicity effect against selected cancer cells, in low potency and is deemed for further investigation to increase its effectiveness against specific cancer cells.

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The role of mesenchymal stem cells in invasivness and metastatic potential of breast cancer cells

10.5176/2345-7821_acmr13.09 ◽

2013 ◽

Author(s):

Lucia Kucerova ◽

Svetlana Skolekova ◽

Martin Bohac ◽

Jozef Fedeles

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Metastatic Potential

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Estrogen-Responsive Genes Overlap with Triiodothyronine-Responsive Genes in a Breast Carcinoma Cell Line

The Scientific World JOURNAL ◽

10.1155/2014/969404 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Nancy Bueno Figueiredo ◽

Sílvia Helena Cestari ◽

Sandro José Conde ◽

Renata Azevedo Melo Luvizotto ◽

Maria Teresa De Sibio ◽

...

Keyword(s):

Breast Carcinoma ◽

Dna Microarrays ◽

Expression Patterns ◽

Breast Adenocarcinoma ◽

Breast Carcinoma Cell Line ◽

Expression Of Genes ◽

Adenocarcinoma Cells ◽

Pericentriolar Material ◽

Mcf 7

It has been well established that estrogen plays an important role in the progression and treatment of breast cancer. However, the role of triiodothyronine (T3) remains controversial. We have previously shown its capacity to stimulate the development of positive estrogen receptor breast carcinoma, induce the expression of genes (PR, TGF-alpha) normally stimulated by estradiol (E2), and suppress genes (TGF-beta) normally inhibited by E2. Since T3regulates growth hormones, metabolism, and differentiation, it is important to verify its action on other genes normally induced by E2. Therefore, we used DNA microarrays to compare gene expression patterns in MCF-7 breast adenocarcinoma cells treated with E2and T3. Several genes were modulated by both E2and T3in MCF-7 cells (Student’st-test,P<0.05). Specifically, we found eight genes that were differentially expressed after treatment with both E2and T3, includingamphiregulin, fibulin 1, claudin 6, pericentriolar material 1, premature ovarian failure 1B, factor for adipocyte differentiation-104, sterile alpha motif domain containing 9, and likely ortholog of rat vacuole membrane protein 1(fold change > 2.0, pFDR < 0.05). We confirmed our microarray results by real-time PCR. Our findings reveal that certain genes in MCF-7 cells can be regulated by both E2and T3.

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Role of DNA hypomethylation in the development of the resistance to doxorubicin in human MCF-7 breast adenocarcinoma cells

Cancer Letters ◽

10.1016/j.canlet.2005.01.038 ◽

2006 ◽

Vol 231 (1) ◽

pp. 87-93 ◽

Cited By ~ 49

Author(s):

Vasil F. Chekhun ◽

Galina I. Kulik ◽

Olga V. Yurchenko ◽

Volodymyr P. Tryndyak ◽

Igor N. Todor ◽

...

Keyword(s):

Breast Adenocarcinoma ◽

Dna Hypomethylation ◽

Adenocarcinoma Cells ◽

Resistance To Doxorubicin ◽

Mcf 7

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Loss of hexokinase 1 sensitizes ovarian cancer to high-dose metformin

Cancer & Metabolism ◽

10.1186/s40170-021-00277-2 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Daniela Šimčíková ◽

Dominik Gardáš ◽

Kateřina Hložková ◽

Martin Hruda ◽

Petr Žáček ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Strong Increase ◽

Ovarian Cancer Cells ◽

High Dose ◽

Ovarian Adenocarcinoma ◽

Adenocarcinoma Cells ◽

Branched Amino Acids ◽

Proliferation Assays

Abstract Background Hexokinases (HKs) are well-studied enzymes catalyzing the first step of glycolysis. However, non-canonical regulatory roles of HKs are still incompletely understood. Here, we hypothesized that HKs comprise one of the missing links between high-dose metformin and the inhibition of the respiratory chain in cancer. Methods We tested the isoenzyme-specific regulatory roles of HKs in ovarian cancer cells by examining the effects of the deletions of HK1 and HK2 in TOV-112D ovarian adenocarcinoma cells. We reverted these effects by re-introducing wild-type HK1 and HK2, and we compared the HK1 revertant with the knock-in of catalytically dead HK1 p.D656A. We subjected these cells to a battery of metabolic and proliferation assays and targeted GC×GC-MS metabolomics. Results We found that the HK1 depletion (but not the HK2 depletion) sensitized ovarian cancer cells to high-dose metformin during glucose starvation. We confirmed that this newly uncovered role of HK1 is glycolysis-independent by the introduction of the catalytically dead HK1. The expression of catalytically dead HK1 stimulated similar changes in levels of TCA intermediates, aspartate and cysteine, and in glutamate as were induced by the HK2 deletion. In contrast, HK1 deletion increased the levels of branched amino acids; this effect was completely eliminated by the expression of catalytically dead HK1. Furthermore, HK1 revertants but not HK2 revertants caused a strong increase of NADPH/NADP ratios independently on the presence of glucose or metformin. The HK1 deletion (but not HK2 deletion) suppressed the growth of xenotransplanted ovarian cancer cells and nearly abolished the tumor growth when the mice were fed the glucose-free diet. Conclusions We provided the evidence that HK1 is involved in the so far unknown glycolysis-independent HK1–metformin axis and influences metabolism even in glucose-free conditions.

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Free Radicals as a Double-Edged Sword: The Cancer Preventive and Therapeutic Roles of Curcumin

Molecules ◽

10.3390/molecules25225390 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5390

Author(s):

Nehal Gupta ◽

Kshitij Verma ◽

Sarath Nalla ◽

Alok Kulshreshtha ◽

Rajiv Lall ◽

...

Keyword(s):

Free Radicals ◽

Cancer Cells ◽

The Body ◽

Chemotherapeutic Drugs ◽

Protein Markers ◽

Dual Nature ◽

Beneficial Effects ◽

Cancer Cell Death ◽

Anticancer Effects

Free radicals, generally composed of reactive oxygen species (ROS) and reactive nitrogen species (RNS), are generated in the body by various endogenous and exogenous systems. The overproduction of free radicals is known to cause several chronic diseases including cancer. However, increased production of free radicals by chemotherapeutic drugs is also associated with apoptosis in cancer cells, indicating the dual nature of free radicals. Among various natural compounds, curcumin manifests as an antioxidant in normal cells that helps in the prevention of carcinogenesis. It also acts as a prooxidant in cancer cells and is associated with inducing apoptosis. Curcumin quenches free radicals, induces antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), and upregulates antioxidative protein markers–Nrf2 and HO-1 that lead to the suppression of cellular oxidative stress. In cancer cells, curcumin aggressively increases ROS that results in DNA damage and subsequently cancer cell death. It also sensitizes drug-resistant cancer cells and increases the anticancer effects of chemotherapeutic drugs. Thus, curcumin shows beneficial effects in prevention, treatment and chemosensitization of cancer cells. In this review, we will discuss the dual role of free radicals as well as the chemopreventive and chemotherapeutic effects of curcumin and its analogues against cancer.

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