scholarly journals Effects of Metformin on Bone-derived Mesenchymal Stromal Cell–breast Cancer Cell Line Interactions

Author(s):  
Maryana Teufelsbauer ◽  
Clemens Lang ◽  
Adelina Plangger ◽  
barbara Rath ◽  
Doris Moser ◽  
...  

Abstract Metformin is used to treat patients with diabetes mellitus and that was found to lower the incidence of cancer. The present study investigated the effects of metformin on human bone-derived mesenchymal stromal cells (BM-MSC) and their breast cancer cell line interactions. BM-MSCs were tested for growth stimulation and migration controlling activity on four breast cancer cell lines employing MTT tests, migration scratch tests and assays of the expression of adipokines in Western Blot arrays. Compared to breast cancer cell lines, metformin significantly inhibited the proliferation of BM-MSC lines. Pretreatment of BM-MSCs with metformin showed variable effects on breast cancer cell lines depending on the specific BM-MSC cancer line combination. Metformin significantly impaired the migration of MDA-MB-231 and MDA-MB-436 in response to conditioned media (CM) of drug pretreated BM-MSCs. Metformin-induced alterations of adipokines by BM-MSC CM indicated increased osteogenic signaling and possibly impairment of metastasis. The anticancer activities of metformin seem to be the result of direct and indirect mechanisms. A lower metformin-induced protumor activity of BM-MSCs in the bone microenvironment seem to contribute to the anticancer effects of this drug in breast cancer patients.

2021 ◽  
Author(s):  
Maryana Teufelsbauer ◽  
Clemens Lang ◽  
Adelina Plangger ◽  
Barbara Rath ◽  
Doris Moser ◽  
...  

Abstract Metformin is used to treat patients with type 2 diabetes mellitus and was found to lower the incidence of cancer. Bone metastasis is a common complication of advanced breast cancer. The present study investigated the effects of metformin on human bone-derived mesenchymal stromal cells (BM-MSC) – breast cancer cell line interactions. BM-MSCs grown from box chisels were tested for growth-stimulating and migration-controlling activity on four breast cancer cell lines either untreated or after pretreatment with metformin. Growth stimulation was tested in MTT tests and migration in scratch assays. Furthermore, the expression of adipokines of BM-MSCs in response to metformin was assessed using Western blot arrays. Compared to breast cancer cell lines (3.6 ± 1.4% reduction of proliferation), 500 µM metformin significantly inhibited the proliferation of BM-MSC lines (12.3 ± 2.2 reduction). Pretreatment of BM-MSCs with metformin showed variable effects of the resulting conditioned media (CM) on breast cancer cell lines depending on the specific BM-MSC –cancer line combination. Metformin significantly impaired the migration of breast cancer cell lines MDA-MB-231 and MDA-MB-436 in response to CM of drug-pretreated BM-MSCs. Assessment of metformin-induced alterations in expression of adipokines by BM-MSC CM indicated increased osteogenic signaling and possibly impairment of metastasis. In conclusion, the anticancer activities of metformin are the result of a range of direct and indirect mechanisms that lower tumor proliferation and progression. A lower metformin-induced protumor activity of BM-MSCs in the bone microenvironment seem to contribute to the positive effects of the drug in selected breast cancer patients.


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 64-64
Author(s):  
N. Song ◽  
S. D. Rice ◽  
D. Gingrich ◽  
D. Wang ◽  
C. Tian ◽  
...  

64 Background: While various multi-gene predictors (MGPs) of chemotherapy response have been developed based on cancer patient primary tissues or cancer cell-lines, the accuracy and consistency of these predictors remain a concern in clinical validation studies. In this study we developed four unique MGPs for chemotherapy response from breast cancer cell lines and performed a systematic evaluation of the performance of these MGPs using data from five distinct clinical trials. Methods: Forty-six immortalized breast cancer cell-lines were exposed to various concentrations of drug combinations [paclitaxel, 5-fluorouracil, doxorubicin, cyclophosphamide (TFAC); 5-fluorouracil, doxorubicin, cyclophosphamide (FAC); 5-fluorouracil, epirubicin, cyclophosphamide (FEC) and epirubicin, cyclophosphamide (EC)] using an in vitro chemosensitivity assay. Utilizing publicly available breast cancer cell-line microarray data, genes highly associated with in vitro chemosensitivity were selected as candidate MGPs. Five independent and publicly available clinical trials were used for validation. In three of these clinical trials patients were treated by TFAC, while EC, FAC or FEC were used in the other two trials. All five studies involved neoadjuvant chemotherapy treatment, and pathologic complete response (pCR) was used as the endpoint. The association of MGPs with pCR was assessed using receiver-operator curve (ROC) analysis and area under the ROC (AUC) was used to evaluate the performance of prediction. Results: In five independent clinical trials, the MGPs predicted patient pCR to EC, FAC/FEC and three TFAC treatments with an AUC of, 0.671, 0.632, 0.735, 0.738 and 0.647 respectively. Conclusions: In the five independent clinical trials in which patients were treated by various chemotherapy agents, the performance of MGPs is promising. These results demonstrate the feasibility of using breast cancer cell-line derived MGPs to predict breast cancer patients’ chemotherapy responses.


Author(s):  
Xiaorong Tang ◽  
Ling Yao ◽  
Keying Chen ◽  
Xiaofang Hu ◽  
Lisa X. Xu

The secretome of cancer cell lines provides promising pool for the identification of candidates for cancer biomarkers. Simple and effective proteomics method to identify secreted proteins is highly desired [1, 2].


RSC Advances ◽  
2016 ◽  
Vol 6 (103) ◽  
pp. 101415-101429 ◽  
Author(s):  
Pooja Ghosh ◽  
Sudipta Bag ◽  
Atanu Singha Roy ◽  
Elavarasan Subramani ◽  
Koel Chaudhury ◽  
...  

Mor-HSA-NPs and EC-HSA-NPs are effective on MDA-MB-468 breast cancer cell lines.


2017 ◽  
Vol 63 (1) ◽  
pp. 141-145
Author(s):  
Yuliya Khochenkova ◽  
Eliso Solomko ◽  
Oksana Ryabaya ◽  
Yevgeniya Stepanova ◽  
Dmitriy Khochenkov

The discovery for effective combinations of anticancer drugs for treatment for breast cancer is the actual problem in the experimental chemotherapy. In this paper we conducted a study of antitumor effect of the combination of sunitinib and bortezomib against MDA-MB-231 and SKBR-3 breast cancer cell lines in vitro. We found that bortezomib in non-toxic concentrations can potentiate the antitumor activity of sunitinib. MDA-MB-231 cell line has showed great sensitivity to the combination of bortezomib and sunitinib in vitro. Bortezomib and sunitinib caused reduced expression of receptor tyrosine kinases VEGFR1, VEGFR2, PDGFRa, PDGFRß and c-Kit on HER2- and HER2+ breast cancer cell lines


2016 ◽  
Vol 63 (3) ◽  
Author(s):  
Karolina Kowalska ◽  
Magdalena Nowakowska ◽  
Kamila Domińska ◽  
Agnieszka W. Piastowska-Ciesielska

The aim of this study was to evaluate the coexpression of caveolin-1 (CAV-1), angiotensin II type 1 receptor (AT1-R) and forkhead box Ml (FOXM1) in prostate and breast cancer cell lines, in comparison with normal cell lines. CAV-1, AT1-R and FOXM1 expression was determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis in the prostate cancer cell lines PC3, DU145 and LNCaP; prostate normal cell line PNT1A; breast cancer cell lines MCF-7 and MDA-MB-231; and the normal breast cell line 184A1. A correlation between the expression levels of the investigated genes and their metastatic properties was determined by the Spearman's rank test (P<0.05) and Aspin-Welsch t-test, respectively. In prostate cell lines, a significant correlation was noted between CAV-1 and AT1-R expression and between FOXM1 and CAV-1 expression. A correlation between the expression levels of the investigated genes and their metastatic potential was also observed, with relatively high expression of all the investigated genes in the normal prostate cell line PNT1A. In comparison to prostate cancer cell lines, an adverse dependency between CAV-1, AT1-R, FOXM1 expression and metastatic potential was observed in the breast cancer cell lines. Relatively high expression of all tested genes was observed in the normal breast cell line 184A1, which was decreasing respectively with increasing metastatic potential of breast cancer cell lines. The results obtained here indicate that CAV-1, FOXM1 and AT1-R may be potential markers of tumorigenesis in certain types of cancer in vitro.


2000 ◽  
Vol 68 (4) ◽  
pp. 369-377 ◽  
Author(s):  
S.N. Pandeya ◽  
P. Yogeeswari ◽  
E.A. Sausville ◽  
A.B. Mauger ◽  
V.L. Narayanan

Various 4-substituted phenyl semicarbazone derivatives were synthesized and evaluated in vitro by NCI in the 3-cell line, one dose primary anticancer assay. Three compounds showed significant activity against breast MCF7 cell line and were further evaluated for potential anticancer activity in an in vitro human disease-oriented tumour cell line screening panel that consisted of 60 human tumour cell lines arranged in nine subpanels, representing diverse histologies. Leukemia, colon, ovarian and breast cancer cell lines were relatively more sensitive to these compounds than the other cell lines. The 4-carboxy substituted p-nitrobenzylidene phenyl semicarbazone (1c) emerged as the most active compound with average GI50 value (the molar drug concentration required for the 50% growth inhibition) of 28.6µM. This compound showed greater activity than methotrexate against NCI-H226(Lung), BT-549 and T-47D(Breast) cancer cell lines.


2021 ◽  
Author(s):  
Maged Mostafa Mahmoud ◽  
Ahmed M. Al-Hejin ◽  
Turki S. Abujamel ◽  
Modhi Alenezi ◽  
Fadwa Aljoud ◽  
...  

Abstract This study served as the pioneer in studying the anti-cancer role of chicken cathelicidin peptides. Chicken cathelicidins were used as anticancer agent against the breast cancer cell line (MCF-7) and human colon cancer cell line (HCT116). An in vivo investigation was also achieved to evaluate the role of chicken cathelicidin in Ehrlich ascites cell (EAC) suppression as a tumor model after subcutaneous implantation in mice. In addition, the mechanism of action of the interaction of cationic peptides with breast cancer cell line MCF-7 was also investigated. It was found during the study that exposure of cell lines to higher concentration of chicken cathelicidin for 72 h reduced cell lines growth rate by 90%-95%. These peptides demonstrated down-regulation of (cyclin A1 and cyclin D genes) which are essential for G1/S phase transient and S/G2 phase and consequently causes “prometaphase arrest” ultimately leading to death of MCF-7 cells. The study showed two- and three-times higher expression of the caspase-3, and − 7 genes respectively in MCF-7 cells treated with chicken peptides (especially cathelicidin-2 and − 3) relative to untreated cells which encouraged pro-apoptotic pathway, autophagy, and augmentation of the anti-proliferative activity. Our data showed that chicken ( CATH-1 ) enhance releasing of TNFα, INF-γ and upregulation of granzyme K in treated mice groups, in parallel, the tumor size and volume was reduced in the treated EAC-bearing groups after cathelicidin administration compared to untreated EAC-bearing group. Additionally, animals received high dose of cathelicidin-1 (40 µg/ml) displayed an apical survival rate compared to untreated carcinoma control and animals which received low dose of cathelicidin (10 and 20 µg/ml). Tumor of mice groups treated with chicken cathelicidin displayed high area of necrosis compared to untreated EAC-bearing mice. Based on histological analysis and immunohistochemical staining revealed that the tumor section in Ehrlich solid tumor exhibited a strong Bcl2 expression in untreated control compared to mice treated with 10 & 20 µg/ml of cathelicidin. Interestingly, low expression of Bcl2 were observed in mice taken 40 µg/ml of CATH-1. This study drive intention in treatment of cancer through the efficacy of anticancer efficacy of chicken cathelicidin peptides.


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