Effects of targeting highly expressed in cancer protein 1 (Hec1) inhibitor INH 1 in breast cancer cell lines In Vitro.

In the present study, the in vitro antiproliferative effect of targeting highly expressed cancer protein 1 (Hec1) inhibitor INH1 was investigated in estrogen receptor-positive MCF-7 cell line originating from an in situ carcinoma and triple negative MDA-MB-231 cell line originating from metastatic carcinoma. Cell viability, xCELLigence RTCA DP instrument CI values, MI, BrdU proliferation assay, and AI analyses were employed for this purpose. According to the findings of the current study, INH1 altered cell proliferation by lowering cell viability, CI, MI values, and BrdU proliferation while raising AI values in both cell lines. Between the experimental and control groups, there were noticeable changes (p<0.05). These findings imply that INH1's mode of action is not dependent on the presence of estrogen receptors, making it a potentially effective therapy for breast cancer.

Investigation of the Effects of the Endogenous Cannabinoid Anandamide on Luminal A Breast Cancer Cell Line MCF-7.

The present study was carried out to investigate anti-tumoral effects of Anandamide (AEA) in luminal A breast cancer cell line MCF-7. Cell viability was measured by MTT assay and cell index was measured by xCelligence DP analyzer system. The Feulgen method was used to determine the mitotic index parameter, and the 3H-Thymidine method was used to determine the labeling index parameter. The apoptotic index parameter was determined using a fluorescent dye DAPI. The results of this study showed that 25 µM Anandamide concentration was the optimum concentration for MCF-7 cells. While this concentration decreased the proportion of cells in the mitotic phase and synthesis phase, it increased the proportion of apoptotic cells.

Antitumor Activity of Tubulin-Binding Agent MPC-6827 on Different Types of Cancer Cell Lines.

In this study, the antitumor effects of tubulin-binding agent MPC-6827 on HeLa, MCF-7 and A549 cell lines originated from cervix carcinoma, metastatic breast adenocarcinoma and adenocarcinomic human alveolar basal epithelial cells respectively were determined. Cell index, BrdU labelling index, mitotic index and apoptotic index were evaluated in experiments. In cell index experiment 2 nM, 4 nM, 6 nM, 8 nM, 10 nM MPC-6827 applied to three cell lines. These parameters showed that 4 nM was the optimum concentration for HeLa and A549 cells, while 2 nM was the optimum concentration for MCF-7 cells. The use of optimum concentrations for each cell line has shown that while there was a significant decrease in mitotic index, BrdU labelling index, there was a significant increase in apoptotic index.

Antiproliferative Effects of EGFR inhibitor Cetuximab and PARP Inhibitor Combination on Non-Small Cell Lung Cancer Cell Line A549 and Cervical Cancer Cell Line HeLa.

In this study, the efficacy of Cetuximab and Parp inhibitor (Parp 1 inhibitor)  used in targeted therapies, alone or in combination, on non-small cell lung cancer cell line A549 and cervical cancer cell line HeLa cells were evaluated. For this purpose different cell kinetic parameters were used. Cell viability, mitotic index, BrdU labelling index and apoptotic index were evaluated in experiments. In single applications Cetuximab at concentrations ranging from 1 mg/ml to 10 mg/ml and Parp inhibitor at concentrations 5 µM -7 µM - 10 µM were applied. IC50 concentration of Cetuximab for A549 was 1 mg/ml, the IC50 concentration of Cetuximab for HeLa was 2 mg/ml, the IC50 concentration of Parp inhibitor for A549 was 5 µM, and the IC50 concentration of Parp inhibitor for HeLa was 7 µM. In both single and combinations, there was a significant decrease in cell viability, mitotic index, BrdU labelling index and there was a significant increase in apoptotic index. A comparison of cetuximab, PARPi and combination applications showed the superiority of combined applications over single applications in all cell kinetic parameters used.

An Overview of the Effect of the Wnt Signaling Pathway in Lung Cancer.

Wnt signal is known to play a significant role in many cellular processes such as cell proliferation, survival, self-renewal, and differentiation. This pathway has been linked to various types of cancer after the definition of mutations and various dysfunctions after the discovery of this pathway. Lung cancer is a type of maligned cancer caused by the deterioration of cellular homeostasis due to various reasons, such as the unbalanced proliferation of cells in the lung, gene expression change, epigenetic factors, and mutation accumulation. It is the most common type of cancer among all types of cancer. There are also various intracellular signal transmission pathways known to be active or inactive in cancer. Although the role of the Wnt signaling pathway in lung cancer development has not yet been clearly clarified, its role in the development and treatment of cancer is seen as very important. Active Wnt signaling or Wnt-1 is overexpressed in lung cancer. Therefore, targeting the Wnt signal pathway is important in cancer treatment, especially lung cancer. Because by creating a minimal effect on somatic cells, inhibiting tumor growth, and preventing resistance to classic treatment methods such as chemotherapy, radiotherapy is necessary for the treatment of disease. New treatment methods developed to target these changes will find a cure for lung cancer. In fact, its incidence may be reduced.

Can mesenchymal stem cells be used to treat COVID-19-induced pneumonia? (Review).

The novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which has resulted in the COVID-19 pandemic, infection by which is commonly characterized by a sore throat, fever and cough, was first reported in Wuhan, China on 31st December 2019. This novel disease is mild in certain individuals, usually younger healthy individuals, whereas the elder and those with underlying health conditions develop severe symptoms and may die as a result of the disease or associated complications. Along with pneumonia, hypercytokinemia, also termed a cytokine storm, is one of the most common pathologies observed in patients with COVID-19. As patients react to the infection with the virus differently; in certain individuals, a cytokine storm may result in death. At present, there is no cure or widely available vaccine for the novel coronavirus. However, it has been hypothesized that mesenchymal stem cells may assist in the treatment/management of the cytokine storm due to their immunomodulating properties.

Bioproduction, structure elucidation and in vitro antiproliferative effect of eumelanin pigment from Streptomyces parvus BSB49.

In this study, the structure of the purified extracellular eumelanin pigment isolated from Streptomyces spp. was elucidated by detailed analysis via two different spectroscopic techniques (FT-IR and NMR). In vitro antiproliferative effects of eumelanin were evaluated on HeLa cell line. These experiments were carried out with the evaluation of the parameters including cell viability, cell index, and mitotic index. With the cell viability and cell index, IC50 concentration of eumelanin was determined as 10 µM. This result showed that the IC50 concentration of eumelanin decreased the values of cell viability, cell index and mitotic index. These changes are statistically significant (p < 0.01). The ability of the dissolved eumelanin (250 µg mL-1) to scavenge free radicals was determined via DPPH and ABTS and was shown to be about 87.73% and 75.2%, respectively, compared with standard antioxidants. It was observed that dry weights of eumelanin yield among the selected strains ranged from 160 to 240 mg L-1. The strain with the highest production potential was selected for 16S rDNA sequence analysis and, accordingly, the selected strain BSB49 was identified as Streptomyces parvus and the sequence analysis results were deposited in NCBI under accession number MK894155.

Evaluation of the cytotoxic effect of Ly2109761 on HeLa cells using the xCELLigence RTCA system.

In the present study, the in vitro cytotoxic effect of a novel transforming growth factor-ß receptor inhibitor, LY2109761, was investigated in the human cervix carcinoma HeLa cell lines. For the purpose of the present study, cell index values obtained using the xCELLigence Real-Time Cell Analysis DP instrument, and mitotic, labelling and apoptotic index analysis were used. The results of the present study indicated that LY2109761 affected the cytoskeleton of HeLa cells, decreased the mitotic and labelling index values of the HeLa cell line, and increased the apoptotic index values. Significant differences were observed between the control group which was not treated with LY2109761 and the experimental groups, which were treated with LY2109761 (P<0.01). The results of the present study suggest that LY2109761 may serve as a promising treatment option for cervix carcinoma.

In vitro antiproliferative effects of nab-paclitaxel with liposomal cisplatin on MDA-MB-231 and MCF-7 breast cancer cell lines.

PURPOSE: In this study, the in vitro cytotoxic effect of nanotechnological drugs nab-paclitaxel and liposomal cisplatin combination was evaluated on MDA-MB-231 and MCF-7 breast cancer cell lines. METHODS: For this purpose cell viability, cell index values obtained from xCELLigence RTCA (Real-Time Cell Analysis) DP instrument, mitotic index (MI), apoptotic index (AI) and labelling index (LI) analysis among cell kinetic parameters were used. A1L25: 1 µg/ml nab-paclitaxel+25 µg/ml liposomal cisplatin, A1L5: 1 µg/ml nab-paclitaxel+5 µg/ml liposomal cisplatin and A10L5: 10 µg/ml nab-paclitaxel+5 µg/ml liposomal cisplatin for MDA-MB-231 cell line and A1L5: 1 µg/ml nab-paclitaxel+5 µg/ml liposomal cisplatin, A1L10: 1 µg/ml nab-paclitaxel+10 µg/ml liposomal cisplatin and A5L1: 5 µg/ml nab-paclitaxel+1 µg/ml liposomal cisplatin doses for MCF-7 were applied for 24-72 hrs. RESULTS: Significant decrease in cell viability and cell index values for both cell lines was observed, while the MI and LI values of both cell lines increased at 24 hrs, and decreased significantly at 72 hrs. Also there was a significant increase in the AI values. CONCLUSIONS: Nab-paclitaxel and liposomal cisplatin offer a promising treatment modality in different breast cancer subtypes.

In vitro cytotoxic effect of tyrosine kinase inhibitor sunitinib malate alone and in combination with hyperthermia on breast adenocarcinoma MCF-7 cells.

PURPOSE: In this study, the in vitro cytotoxic effect of sunitinib malate alone and combination with hyperthermia was evaluated on MCF-7 cells (human breast adenocarcinoma cell line). METHODS: For this purpose cell proliferation assay, mitotic index and labelling index analysis among cell kinetic parameters were assessed. Sunitinib malate doses of 1, 5 and 10 µM were applied alone and in combination with hyperthermia to cells for 24-72 hrs. RESULTS: A significant decrease (p<0.05) was noticed in cell proliferation, mitotic index and labelling index for all experimental groups and for all applications. CONCLUSION: Labeling index and mitotic index values show that sunitinib malate combined with hyperthermia was significantly more effective in MCF-7 cells than when given alone. This combination acts through synergistic and additive effects.

Clinical significance of epithelial-mesenchymal transition and cancer stem cells.

Purpose: Spread of cancer cells from the organ of the origin of them to another location, namely metastasis, is one of the most important factors that complicate the treatment of cancer. Therefore, research for the treatment of metastatic disease is gaining importance, especially for advanced cancers. This research focuses on the mechanisms that facilitate the metastatic tendency of cancer cells. Therefore, epithelial-mesenchymal transition (EMT) mechanism that helps the cells become metastatic and cancer stem cells (CSCs) present in the heterogeneous tumor mass are in the center of these researches.

Effects of metformin on cell kinetic parameters of MCF-7 breast cancer cells in vitro.

In this study, the antiproliferative effects of the metformin was evaluated on MCF-7 Cells (human breast adenocarcinoma cell line). For this purpose cell kinetic parameters including cell proliferation assay, mitotic index and labelling index analysis were used. 30 µM, 65 µM and 130 µM Metformin doses were applied to cells for 24, 48 and 72 hours. The results showed that there was a significant decrease in cell proliferation, mitotic index and labelling index for all experimental groups (p<0.05) for all applications.

Effects of hypobaric conditions on apoptosis signalling pathways in HeLa cells.

Nowadays increasing effectiveness in cancer therapy and investigation of formation of new strategies that enhance antiproliferative activity against target organs has become a subject of interest. Although the molecular mechanisms of apoptosis can not be fully explained, it is known that cell suicide program existing in their memory genetically is activated by pathophysiological conditions and events such as oxidative stress. Low pressure (hypobaric) conditions that create hypoxia promote apoptosis by inhibiting cell cycling. In this study, determination of the effects of fractional hypobaric applications at different times on HeLa cells at cellular and molecular levels were targeted. Experiments were carried out under hypobaric conditions (35.2 kPa) in a specially designed hypobaric cabin including 2% O2 and 98% N. Application of fractional hypobaric conditions was repeated two times for 3 hours with an interval of 24 hours. At the end of the implementation period cells were allowed to incubate for 24 hours for activation of repair mechanisms. Cell kinetic parameters such as growth rate (MTT) and apoptotic index were used in determination of the effect of hypobaric conditions on HeLa cells. Also in our study expression levels of the Bcl-2 gene family that have regulatory roles in apoptosis were determined by the RT-PCR technique to evaluate molecular mechanisms. The results showed that antiproliferative effect of hypobaric conditions on HeLa cells started three hours from the time of application and increased depending on the period of exposure. While there was a significant decrease in growth rate values, there was a significant increase in apoptotic index values (p<0.01). Also molecular studies showed that hypobaric conditions caused a significant increase in expression level of proapoptotic gene Bax and significant decrease in antiapoptotic Bfl-1. Consequently fractional application of hypobaric conditions on HeLa cell cultures increased both antiproliferative and apoptotic effects and these effects were triggered by the Bax gene.

Endpoint of cancer treatment: targeted therapies.

Nowadays there are several limitations in cancer treatment. One of these is the use of conventional medicines which not only target cancer cells and thus also cause high toxicity precluding effective treatment. Recent elucidation of mechanisms that cause cancer has led to discovery of novel key molecules and pathways which have have become successful targets for the treatments that eliminate only cancer cells. These so-called targeted therapies offer new hope for millions of cancer patients, as briefly reveiwed here focusing on different types of agents, like PARP, CDK, tyrosine kinase, farnysyl transferase and proteasome inhibitors, monoclonal antibodies and antiangiogenic agents.

Triple negative breast cancer.

Triple-negative breast cancers (TNBC), characterized by absence of the estrogen receptor (ER) and progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), have a poor prognosis. To overcome therapy limitations of TNBC, various new approaches are needed. This mini-review focuses on discovery of new targets and drugs which might offer new hope for TNBC patients.

Effects of femara and tamoxifen on proliferation of FM3A cells in culture.

In this study, antiproliferative effects of the selective estrogen receptor modulator Tamoxifen and the aromatase inhibitor letrozole (Femara) were evaluated and compared using the FM3A cell line, originating from a C3H mouse mammary carcinoma and positive in terms of estrogen receptor (ER) expression. Cell kinetic parameters including labelling index, mitotic index and labelling index were assessed after exposure of the. FM3A cell line to 0.001µg/ml of Tamoxifen and 0.25µg/ml of Femara for 4, 8, 16 and 32 h for all parameters. The results showed that cell growth was inhibited by both agents. There was a significant decrease in labelling index and mitotic index and significant increase in apoptotic index for all experimental groups. The differences between control and all experimental groups were statistically significant (p<0.001) for all applications.