scholarly journals Taxifolin Resensitizes Multidrug Resistance Cancer Cells via Uncompetitive Inhibition of P-Glycoprotein Function

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3055 ◽  
Author(s):  
Hsiu-Ju Chen ◽  
Yun-Lung Chung ◽  
Chia-Ying Li ◽  
Ying-Tzu Chang ◽  
Charles Wang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Uncompetitive Inhibition ◽  
P Glycoprotein

P-glycoprotein (P-gp) effluxes lots of chemotherapeutic agents and leads to multidrug resistance (MDR) in cancer treatments. The development of P-gp inhibitors from natural products provide a potential strategy for the beneficial clinical outcomes. This study aimed to evaluate the effects of the natural flavonoid taxifolin, luteolin, (−)-gallocatechin, and (−)-catechin on human P-gp activity. The kinetic interactions and underlying mechanisms of taxifolin-mediated transporter inhibition were further investigated. The transporter inhibition ability was evaluated in human P-gp stable expression cells (ABCB1/Flp-InTM-293) by calcein-AM uptake assays. The kinetics study for P-gp inhibition was evaluated by doxorubicin and rhodamine123 efflux assays. The MDR reversal ability of taxifolin were performed by SRB assays to detect the cell viability in sensitive cancer cell line (HeLaS3), and resistant cancer cell line (KB-vin). Cell cycle analysis and ABCB1 real-time RT-PCR were used for mechanical exploration. The results demonstrated that taxifolin decreased ABCB1 expression in a concentration-dependent manner. The function of P-gp was inhibited by taxifolin through uncompetitive inhibition of rhodamine 123 and doxorubicin efflux. The combination of taxifolin significantly resensitized MDR cancer cells to chemotherapeutic agents. These results suggested that taxifolin may be considered as a potential P-gp modulator for synergistic treatment of MDR cancers.

scholarly journals Non-P-glycoprotein-mediated Atypical Multidrug Resistance in a Human Bladder Cancer Cell Line

1995 ◽  
Vol 86 (11) ◽  
pp. 1112-1118 ◽  
Author(s):  
Seiji Naito ◽  
Shuji Hasegawa ◽  
Akira Yokomizo ◽  
Hirofumi Koga ◽  
Shuji Kotoh ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Multidrug Resistance ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Bladder Cancer Cell Line ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Human Bladder Cancer Cell ◽  
P Glycoprotein

Reversal Effect of Stephania Tetrandra-Containing Chinese Herb Formula SENL on Multidrug Resistance in Lung Cancer Cell Line SW1573/2R120

2010 ◽  
Vol 38 (02) ◽  
pp. 401-413 ◽  
Author(s):  
Meng Xu ◽  
Liang-He Sheng ◽  
Xi-Hai Zhu ◽  
Shi-Bin Zeng ◽  
Guo-Jun Zhang
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Lung Cancer Cell ◽  
Reversal Effect

This research is aimed on reversing multidrug resistance (MDR) of chemotherapy in lung cancer. According to our previous research, chemotherapeutic drugs resistance in lung cancer is mainly due to high expression of multidrug resistance-associated protein (MRP) gene and activation of caspases. The effect of stephania tetrandra-containing Chinese herbal formula, namely Supplement Energy and Nourish Lung (SENL), is effective in enhancing efficacy and reducing toxicity of chemotherapy in lung cancer. However, the underlying mechnism is largely unknown. To understand whether and how SENL herbs function on multidrug-resistance lung cancer cells, we treated a multidrug resistance lung cancer cell line, SW1573/2R120 with SENL herbs alone or together with a chemotherapeutic drug, Adriamycin (ADM). We observed that SENL herbs had a significant synergistic effect with ADM in inhibiting the growth of SW1573/2R120 cells. SENL alone and particularly together with ADM could significantly increase cell apoptotic death via mitochondria- and caspase-dependent pathway. Furthermore, we showed that SENL herbs could reverse drug resistance of lung cancer cells by decreasing MRP expression and increasing accumulation of intracellular ADM, which in turn increase the sensitivity of cancer cells to ADM. Taken together, the mechanism underlying reversal effect of drug resistance by SENL treatment was reported here and further systematical investigation on SENL herbs may lead to solve drug resistance in lung cancer chemotherapy.

Reversal by a Dihydropyridine Derivative of Non-P-Glycoprotein-Mediated Multidrug Resistance in Etoposide-Resistant Human Prostatic Cancer Cell Line

1995 ◽  
Vol 154 (3) ◽  
pp. 1210-1216 ◽  
Author(s):  
Yoshihisa Tasaki ◽  
Masayuki Nakagawa ◽  
Jiro Ogata ◽  
Akira Kiue ◽  
Hideyuki Tanimura ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cell Line ◽  
Cancer Cell ◽  
Prostatic Cancer ◽  
Cancer Cell Line ◽  
P Glycoprotein ◽  
Dihydropyridine Derivative

scholarly journals Different effects of tryptophan 2,3-dioxygenase inhibition on SK-Mel-28 and HCT-8 cancer cell lines

2020 ◽  
Vol 146 (12) ◽  
pp. 3155-3163
Author(s):  
Sara Paccosi ◽  
Marta Cecchi ◽  
Angela Silvano ◽  
Sergio Fabbri ◽  
Astrid Parenti
Keyword(s):  
Cell Proliferation ◽  
Cell Line ◽  
Cancer Cell ◽  
Cell Function ◽  
Cancer Cell Line ◽  
Colon Cancer Cell Line ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Huvec Cells ◽  
Cell Arrest

Abstract Purpose Indoleamine 2,3-dioxygenase-1 (IDO1) and more recently, tryptophan 2,3-dioxygenase (TDO), are tryptophan-catabolizing enzymes with immunoregulatory properties in cancer. IDO1 is more expressed than TDO in many tumours including melanomas; however, IDO inhibitors did not give expected results in clinical trials, highlighting the need to consider TDO. We aimed to characterize both TDO expression and function in a melanoma cell line, named SK-Mel-28, with the purpose to compare it with a colon cancer cell line, HCT-8, and with a human endothelial cell line (HUVEC). Methods TDO expression was assessed as real time-PCR and western blot, for mRNA and protein expression, respectively. While cell proliferation was assessed as cell duplication, cell apoptosis and cell cycle were analysed by means of flow cytometry. Results SK-Mel-28 cells showed higher TDO levels compared to HCT-8 and to HUVEC cells. A selective TDO inhibitor, 680C91, significantly impaired cell proliferation in a concentration-dependent manner, by inducing cell arrest during the G2 phase for SK-Mel-28 and HUVEC cells, while an early apoptosis was increasing in HCT-8 cells. No toxic effects were observed. These data demonstrated that TDO is highly expressed in SK-Mel-28 cells and may be involved in the regulation of their proliferation. Conclusion TDO may directly modulate cancer cell function rather than immune suppression and can be considered as a target for melanoma progression together with IDO1.

3,4,5-Trihydroxybenzoic Acid Triggered Oxidative Stress in 95-D Lung Cancer Cell Line

2014 ◽  
Vol 926-930 ◽  
pp. 1061-1064
Author(s):  
Yan Li Xi ◽  
Xiang Qun Wu ◽  
Jie Yu ◽  
Wei Guo Xu ◽  
Tong Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Human Lung Cancer ◽  
Dependent Manner ◽  
Lung Cancer Cell

It is a good therapeutic method that add exogenous ROS to trigger oxidative stress causing death of cancer cells. In the present study, we investigated the inhibitory effects of 3,4,5-trihydroxybenzoic acid (TBA), a polyhydroxyphenolic compound, on high metastatic human lung cancer cell line (95-D) based on inducing reactive oxygen species (ROS). The experiments in vitro showed that 95-D cell viability was inhibited by various amounts of TBA and death was induced in a dose-dependent manner. The possible mechanism was that TBA can induce cell death by decreasing mitochondrial membrane potential (MMP; ΔΨm) and increasing hydrogen peroxide (H2O2) level. These results imply that TBA efficiently induces death in 95-D lung cancer cells and that TBA exerts cytotoxicity on cancer cells by its pro-oxidative activity.

scholarly journals Antiproliferative Effect of Epilobium parviflorum Extracts on Colorectal Cancer Cell Line HT-29

2020 ◽  
Author(s):  
M. AYDIN AKBUDAK ◽  
Tevhide SUT ◽  
Nuraniye ERUYGUR ◽  
Ersin AKINCI
Keyword(s):  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Folk Medicine ◽  
Cancer Cell Line ◽  
Fibroblast Cell ◽  
Colorectal Cancer Cell Line ◽  
Dependent Manner ◽  
Ht 29

The Epilobium species are rich in various active phytochemicals and have seen wide use in folk medicine to treat several diseases, including benign prostatic hyperplasia. Although their benefits have been demonstrated on certain types of cancer cells, such as prostate cancer cells, their potential antiproliferative effects on colorectal adenocarcinoma cells have yet to be studied. The present study exhibited the antiproliferative activity of aqueous and ethanolic Epilobium parviflorum extracts in a colon cancer cell line, HT-29 cells in vitro. Both types of extracts reduced the cell viability of HT-29 cells in a dose-dependent manner. A gene expression analysis of the HT-29 cells demonstrated an increase in apoptotic genes, Caspase-3 and Caspase-8. Nuclear fragmentation of the apoptotic cells was also demonstrated through TUNEL assay and immunostaining experiments. On the other hand, the same lethal concentrations of the E. parviflorum extracts did not significantly affect a non-cancerous human fibroblast cell line, BJ cells. Our results confirmed that aqueous and ethanolic Epilobium parviflorum extracts can eliminate proliferation of human colorectal carcinoma cells in vitro. E. parviflorum may have the potential to become a therapeutic agent against colon cancers.

Functional interaction between Smad3 and S100A4 (metastatin-1) for TGF-β-mediated cancer cell invasiveness

2010 ◽  
Vol 426 (3) ◽  
pp. 327-335 ◽  
Author(s):  
Isao Matsuura ◽  
Chen-Yu Lai ◽  
Keng-Nan Chiang
Keyword(s):  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Transforming Growth Factor ◽  
Cancer Cell Line ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Dependent Manner ◽  
Malignant Tumours ◽  
Cell Invasiveness

TGF-β (transforming growth factor-β) induces a cytostatic response in most normal cell types. In cancer cells, however, it often promotes metastasis, and its high expression is correlated with poor prognosis. In the present study, we show that S100A4, a metastasis-associated protein, also called metastatin-1, can physically and functionally interact with Smad3, an important mediator of TGF-β signalling. In agreement with its known property, S100A4 binds to Smad3 in a Ca2+-dependent manner. The S100A4-binding site is located in the N-terminal region of Smad3. S100A4 can potentiate transcriptional activity of Smad3 and the related Smad2. When exogenously expressed in MCF10CA1a.cl1, an MCF10-derived breast cancer cell line, S100A4 increases TGF-β-induced MMP-9 (matrix metalloproteinase-9) expression. On the other hand, depletion of S100A4 by siRNA (small interfering RNA) from the MDA-MB231 cell line results in attenuation of MMP-9 induction by TGF-β. Consistent with these observations, S100A4 increases cell invasion ability induced by TGF-β in MCF10CA1a.cl1 cells, and depletion of the protein in MDA-MB-231 cells inhibits it. Because expression of both S100A4 and TGF-β is highly elevated in many types of malignant tumours, S100A4 and Smad3 may co-operatively increase metastatic activity of some types of cancer cells.

A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer Properties

2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Hepatic Function ◽  
Anticancer Properties ◽  
Mcf 7

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

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