Therapeutic potential of xanthones from Swertia chirata in breast cancer cells

Hyperoside (quercetin 3-o-β-d-galactopyranoside) is one of the flavonoid glycosides with anti-inflammatory, antidepressant, and anti-cancer effects. But it remains unknown whether it had effects on breast cancer. Here, different concentrations of hyperoside were used to explore its therapeutic potential in both breast cancer cells and subcutaneous homotransplant mouse model. CCK-8 and wound healing assays showed that the viability and migration capability of Michigan Cancer Foundation-7 (MCF-7) and 4T1 cells were inhibited by hyperoside, while the apoptosis of cells were increased. Real-time quantitative PCR (qRT-PCR) and western blot analysis were used to detect mRNA and the protein level, respectively, which showed decreased levels of B cell lymphoma-2 (Bcl-2) and X-linked inhibitor of apoptosis (XIAP), and increased levels of Bax and cleaved caspase-3. After exploration of the potential mechanism, we found that reactive oxygen species (ROS) production was reduced by the administration of hyperoside, which subsequently inhibited the activation of NF-κB signaling pathway. Tumor volume was significantly decreased in subcutaneous homotransplant mouse model in hyperoside-treated group, which was consistent with our study in vitro. These results indicated that hyperoside acted as an anticancer drug through ROS-related apoptosis and its mechanism included activation of the Bax–caspase-3 axis and the inhibition of the NF-κB signaling pathway.

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Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism

International Journal of Oncology ◽

10.3892/ijo.2012.1523 ◽

2012 ◽

Vol 41 (3) ◽

pp. 798-804 ◽

Cited By ~ 21

Author(s):

BO-RIM YI ◽

KELVIN J. CHOI ◽

SEUNG U. KIM ◽

KYUNG-CHUL CHOI

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Therapeutic Potential ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Suicide Genes ◽

Tumor Tropism

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C/EBPδ Modulates Cell Growth, Differentiation and Apoptosis of Myeloid Leukemia, Prostate and Breast Cancer Cells.

Blood ◽

10.1182/blood.v104.11.4300.4300 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4300-4300

Author(s):

Sigal Gery ◽

Sakae Stanosaki ◽

Takayuki Ikezoe ◽

Wolf K. Hofmann ◽

Adrian F. Gombart ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Myeloid Leukemia ◽

Breast Cancer Cells ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Critical Role ◽

Leukemic Cells ◽

Granulocytic Differentiation ◽

Mcf 7

Abstract C/EBPδ belongs to the family of highly conserved CCAAT/enhancer binding protein (C/EBP) transcription factors. Members of this family play a critical role in the regulation of mitotic growth arrest and differentiation in numerous cell types. To examine the consequences of C/EPBδ expression, we transfected C/EPBδ into CML myeloid leukemia (KCL22, K562), prostate (LNCaP, PC3, DU145), and breast (MCF-7, T47D, MDA-MB-231) cancer cell lines. C/EBPδ expression resulted in a proliferative arrest and an increase in apoptosis of the myeloid leukemia cells, as well as the prostate cells LNCaP and PC3, and the breast cells MCF-7 and T47D. In contrast, DU145 prostate and MDA-MB-231 breast cancer cells were not inhibited by C/EBPδ, indicating that the biologically properties of C/EBPδ depend upon its cellular context. We further studied the molecular mechanisms underlying the affect of C/EPBδ expression in CML leukemic cells. Myeloid differentiation of KCL22 and K562 blast cells as shown by morphologic changes and induction of secondary specific granule genes, occurred within 4 days of inducing expression of C/EBPδ. Furthermore, expression of C/EBPδ was associated with downregulation of c-Myc and cyclin E, and upregulation of the forkhead transcription factor FoxO1a (FKHR) and the cyclin-dependent kinase inhibitor p27Kip1. In addition, microarray analysis showed that C/EBPδ mRNA is upregulated during granulocytic differentiation of normal CD34+ bone marrow cells, suggesting that C/EBPδ is involved in lineage-specific differentiation. Taken together, these results show that expression of C/EBPδ in BCR-ABL-positive CML cells in blast crisis, is sufficient for neutrophil differentiation and suggest that ectopic induction of C/EBPδ in the blastic phase of CML, as well as in certain cases of prostate and breast cancers, may hold promising therapeutic potential.

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Unacylated ghrelin and AZP531 suppress the 3D growth of breast cancers

10.1101/2020.01.22.915744 ◽

2020 ◽

Author(s):

CheukMan C. Au ◽

John B. Furness ◽

Kara Britt ◽

Sofya Oshchepkova ◽

Heta Ladumor ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Mechanism Of Action ◽

Breast Cancer Cells ◽

Therapeutic Potential ◽

3D Culture ◽

Mapk Signaling ◽

Unacylated Ghrelin ◽

Ghrelin Receptor

ABSTRACTBreast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, it remains the second leading cause of cancer-related death in the US. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. One major area of research relates to its reported effects to increase insulin sensitivity in diabetics, this being the basis for the development of unacylated ghrelin analog, AZP531 or livoletide, now in clinical trials for the treatment of Prader-Willi Syndrome. The mechanism of action of unacylated ghrelin is largely uncharacterized, in any system, because it does not bind to or activate the cognate ghrelin receptor, GHSR1a. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP531. We report potent effects of unacylated ghrelin, at picomolar doses, on the growth of breast cancer cells, dependent on 3D culture and activation of Gαi. Suppression of MAPK signaling by unacylated ghrelin leads to cell cycle arrest and apoptosis. AZP531 also suppresses the growth of breast cancer cells in vitro and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer.

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hTERT Downregulation Attenuates Resistance to DOX, Impairs FAK-Mediated Adhesion, and Leads to Autophagy Induction in Breast Cancer Cells

Cells ◽

10.3390/cells10040867 ◽

2021 ◽

Vol 10 (4) ◽

pp. 867

Author(s):

Aleksandra Romaniuk-Drapała ◽

Ewa Totoń ◽

Natalia Konieczna ◽

Marta Machnik ◽

Wojciech Barczak ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Therapeutic Potential ◽

Telomerase Activity ◽

Telomere Maintenance ◽

Population Doubling ◽

Cell Cycle Distribution ◽

Human Telomerase Reverse Transcriptase ◽

Human Telomerase

Telomerase is known to contribute to telomere maintenance and to provide cancer cell immortality. However, numerous reports are showing that the function of the enzyme goes far beyond chromosome ends. The study aimed to explore how telomerase downregulation in MCF7 and MDA-MB-231 breast cancer cells affects their ability to survive. Consequently, sensitivity to drug resistance, proliferation, and adhesion were assessed. The lentiviral-mediated human telomerase reverse transcriptase (hTERT) downregulation efficiency was performed at gene expression and protein level using qPCR and Western blot, respectively. Telomerase activity was evaluated using the Telomeric Repeat Amplification Protocol (TRAP) assay. The study revealed that hTERT downregulation led to an increased sensitivity of breast cancer cells to doxorubicin which was demonstrated in MTT and clonogenic assays. During a long-term doubling time assessment, a decreased population doubling level was observed. Interestingly, it did not dramatically affect cell cycle distribution. hTERT downregulation was accompanied by an alteration in β1-integrin- and by focal adhesion kinase (FAK)-driven pathways together with the reduction of target proteins phosphorylation, i.e., paxillin and c-Src. Additionally, autophagy activation was observed in MDA-MB-231 cells manifested by alternations in Atg5, Beclin 1, LC3II/I ratio, and p62. These results provide new evidence supporting the possible therapeutic potential of telomerase downregulation leading to induction of autophagy and cancer cells elimination.

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Encapsulation of Quercetin in Tri-Block-Copolymer/Tween 80 Mixed Nanomicelles to Enhance its Cytotoxicity Against Breast Cancer Cells

10.21203/rs.3.rs-1075658/v1 ◽

2021 ◽

Author(s):

Reza Davarnejad ◽

Kiyana Layeghy ◽

Meysam Soleymani ◽

Arvin Ayazi

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Cancer Cells ◽

Drug Delivery System ◽

Delivery System ◽

Breast Cancer Cells ◽

Therapeutic Potential ◽

Tween 80 ◽

Prolonged Release

Abstract Quercetin, a natural polyphenolic compound, has attracted much attention due to its great therapeutic potential against various types of diseases. But clinical applications of quercetin are limited due to its poor aqueous solubility and low bioavailability. The main purpose of this research was to evaluate the therapeutic potential of quercetin-loaded Pluronic F127 (PF127)/Tween 80 mixed nanomicelles as a passive targeted drug delivery system for breast cancer therapy. To this end, quercetin-loaded mixed nanomicelles with different mass ratios of drug:PF127:Tween 80 were prepared by the thin-film hydration method. The highest drug loading and entrapment efficiency were obtained to be 2.3% and 98.0%, respectively, for mixed micelles with drug:PF127:Tween 80 ratio of 1:40:15. The physical interactions of quercetin with PF127 and Tween 80 at optimized ratio was investigated by XRD and FTIR analyses. The mean hydrodynamic size and surface charge of prepared nanomicelles, measured by DLS and zeta potential analyses, were 22.1 nm and -7.63 mV, respectively. The results of in-vitro drug release experiments showed that, the mixed micellar system has a prolong and sustained release behavior compared to the solution of free quercetin. Moreover, the in-vitro cytotoxicity studies of quercetin-loaded mixed nanomicelles on breast cancer cells (MCF-7) revealed that, the encapsulated drug have a lower IC50 value (8.9 µg/mL) compared to the free drug (49.2 µg/mL). Our results suggest that, quercetin-loaded mixed nanomicelles can be considered as a promising drug delivery system with prolonged release and potentiated cytotoxicity against breast cancer cells.

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

10.1101/476812 ◽

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.

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