scholarly journals THE MODULATION OF DRUG EFFLUX TRANSPORTER BY CURCUMIN IN MCF7 BREAST CANCER CELLS AFTER REPEATED EXPOSURE OF ENDOXIFEN AND ESTRADIOL

2018 ◽  
Vol 10 (1) ◽  
pp. 102
Author(s):  
Robby Hertanto ◽  
Wilson Bastian ◽  
Paramita . ◽  
Melva Louisa
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Mrna Expression ◽  
Rna Extraction ◽  
Efflux Transporters ◽  
Drug Efflux ◽  
Mcf7 Cells ◽  
Total Rna ◽  
P Glycoprotein ◽  
Drug Efflux Transporters

Objective: The aim of the present study was to determine whether curcumin (CM) can prevent drug sensitivity of breast cancer (BC) cells when E andβ-E2 are administered together and whether the underlying mechanism involves modulation of drug efflux transporters.Methods: MCF7 BC cells were treated with the vehicle only, E+β-E2, or E+β-E2+CM repeatedly for 8 weeks. Afterward, the cells were harvested,counted, and isolated for total RNA extraction. Total RNA was then processed into cDNA and further processed for the determination of mRNAexpression patterns of drug efflux transporters (P-glycoprotein, BCRP, and MRP1).Results: Decreased sensitivity of BC cells was shown by the increased cell viability of MCF7 cells after 8 weeks. This condition was accompanied withincreased mRNA expression of P-glycoprotein, BCRP, and MRP1 in cells treated with E+β-E2, as compared with the vehicle only. CM, administered incombination with E+β-E2, resulted in decreased cell viability versus E and β-E2 and also decreased in mRNA expression of P-glycoprotein, BCRP, andMRP1.Conclusion: CM partially reversed the sensitivity loss of BC cells to E in the presence of β-E2 by modulating drug efflux transporters.

scholarly journals Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Desak Gede Budi Krisnamurti ◽  
Melva Louisa ◽  
Erlia Anggraeni ◽  
Septelia Inawati Wanandi
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Efflux Transporters ◽  
Drug Efflux ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Short Period ◽  
Drug Efflux Transporters

Tamoxifen is the first line drug used in the treatment of estrogen receptor-positive (ER+) breast cancer. The development of multidrug resistance (MDR) to tamoxifen remains a major challenge in the treatment of cancer. One of the mechanisms related to MDR is decrease of drug influx via overexpression of drug efflux transporters such as P-glycoprotein (P-gp/MDR1), multidrug resistance associated protein (MRP), or BCRP (breast cancer resistance protein). We aimed to investigate whether the sensitivity of tamoxifen to the cells is maintained through the short period and whether the expressions of several drug efflux transporters have been upregulated. We exposed MCF7 breast cancer cells with tamoxifen 1 μM for 10 passages (MCF7 (T)). The result showed that MCF7 began to lose their sensitivity to tamoxifen from the second passage. MCF7 (T) also showed a significant increase in all transporters examined compared with MCF7 parent cells. The result also showed a significant increase of CC50 in MCF7 (T) compared to that in MCF7 (97.54 μM and 3.04 μM, resp.). In conclusion, we suggest that the expression of several drug efflux transporters such as P-glycoprotein, MRP2, and BCRP might be used and further studied as a marker in the development of tamoxifen resistance.

scholarly journals Decreased sensitivity of several anticancer drugs in TMEPAI knockout triple-negative breast cancer cells

2019 ◽  
Vol 28 (2) ◽  
pp. 110-5
Author(s):  
Bantari Wisynu Kusuma Wardhani ◽  
Meidi Utami Puteri ◽  
Yukihide Watanabe ◽  
Melva Louisa ◽  
Rianto Setiabudy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Anticancer Drugs ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Efflux Transporters ◽  
Drug Efflux ◽  
Cancer Resistance ◽  
Expression Levels ◽  
Drug Efflux Transporters

BACKGROUND Transmembrane prostate androgen-induced protein (TMEPAI) was reported to be highly amplified in the majority of patients with triple-negative breast cancer (TNBC). TMEPAI is related to poorer prognosis, limited treatment options, and prone to drug resistance compared with other proteins. One of the established markers to determine cancer resistance to drugs is the increased expression levels of drug efflux transporters. However, the role of TMEPAI in cancer resistance to drugs has not been elucidated. This study was aimed to investigate whether TMEPAI participates in cancer resistance to drugs by regulating drug efflux transporters. METHODS TMEPAI knockout (KO) cells were previously developed from a TNBC cell line, Hs578T (wild-type/WT), using a CRISPR-Cas9 system. The expression levels of drug efflux transporters were determined in Hs578T-KO and Hs578-WT by quantitative reverse transcriptase polymerase chain reaction. Cytotoxic concentration 50% (CC50) of several anticancer drugs (doxorubicin, cisplatin, and paclitaxel) were determined in the two cell lines via 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. RESULTS The results showed that the mRNA expression of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) was significantly increased in Hs578T-KO compared with that in Hs578T-WT cells. CC50 of several anticancer drugs investigated (doxorubicin, paclitaxel, and cisplatin) in Hs578T-KO cells was higher than that in Hs678-WT. CONCLUSIONS TMEPAI participated in the regulation of mRNA expression levels in drug efflux transporters (P-gp, BCRP, and multidrug resistance-associated protein 1). Further studies are necessary to confirm whether this finding might be dependent on the development of cancer cell sensitivity to anticancer agents.

scholarly journals QUERCETIN IMPROVES THE EFFICACY OF SORAFENIB IN TRIPLE NEGATIVE BREAST CANCER CELLS THROUGH THE MODULATION OF DRUG EFFLUX TRANSPORTERS EXPRESSIONS

2019 ◽  
pp. 129-134
Author(s):  
MELVA LOUISA ◽  
BANTARI WK WARDHANI
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Efflux Transporters ◽  
Drug Efflux ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Drug Efflux Transporters

Objective: This study aimed to investigate whether quercetin is able to improve the efficacy of sorafenib in triple negative breast cancer cells and explore the possibility of drug efflux transporters modulation by quercetin. Methods: We exposed MDA-MB-231, a triple negative breast cancer cell line, to several groups: sorafenib alone, quercetin alone, a combination of sorafenib-quercetin, and control. We determined cell viability over control weekly up to 4 w. At the end of the fourth week, mRNA expressions of drug efflux transporters (P-glycoprotein and breast cancer resistance protein [BCRP] and MRP2 [multidrug resistance-associated protein-2]) were examined. Results: Sorafenib alone was shown to maintain its efficacy for only two weeks, while quercetin alone was able to maintain its effect for four weeks. A combination of sorafenib-quercetin showed the best cytotoxicity effects compared with sorafenib or quercetin alone and was able to maintain its efficacy for four weeks. There were increased mRNA expressions of P-glycoprotein, BCRP, and MRP2 after four weeks of treatment with sorafenib, while treatment with quercetin decreased the drug efflux transporters expressions. A combination of sorafenib-quercetin decreased the mRNA expressions of both P-glycoprotein and BCRP, compared with sorafenib alone. Conclusion: We suggest that decreased expressions of both drug efflux transporters, P-glycoprotein and BCRP, mediated by quercetin ameliorate the efficacy of sorafenib in TNBC. Therefore, the addition of quercetin to sorafenib might be useful in the future in improving the therapeutic efficacy of sorafenib in triple negative breast cancer.

Functional intravital assay of anticancer drug efflux transporters in breast cancer biopsy specimens

1998 ◽  
Vol 34 ◽  
pp. S106
Author(s):  
T. Bogush ◽  
G. Smirnova ◽  
E. Koldaeva ◽  
E. Bogush ◽  
V. Kirsanov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Drug ◽  
Efflux Transporters ◽  
Drug Efflux ◽  
Biopsy Specimens ◽  
Cancer Biopsy ◽  
Drug Efflux Transporters

scholarly journals Expression and Correlation of Cell-Free cIAP-1 and cIAP-2 mRNA in Breast Cancer Patients: A Study from India

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Amit Kumar Verma ◽  
Irfan Ahmad ◽  
Prasant Yadav ◽  
Arshad Husain Rahmani ◽  
Bazila Khan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Median Survival ◽  
Patient Survival ◽  
Rna Extraction ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Total Rna ◽  
Distant Organ

Background. Inhibitors of apoptosis proteins such as cIAP-1 and cIAP-2 have recently emerged as the key mechanism in resistance to apoptosis in various cancers and lead to cell survival. Therefore, the present study aimed to evaluate the cIAP-1 and cIAP-2 expression in breast cancer patients, as well as their association with overall patient survival. Methods. Histopathologically confirmed 100 invasive ductal carcinoma patients and healthy controls were included in the present study. Total RNA extraction was done from the serum sample of the patients; further, 100 ng of total RNA was used to synthesise cDNA from patients’ as well as from healthy controls’ serum. Quantitative real-time PCR was performed using the maxima SYBR Green dye to study the expression of cIAP-1 and cIAP-2, and beta-actin was used as the internal control. Results. The study observed that breast cancer patients had 13.50 mean fold increased cIAP-1 mRNA and 8.76 mean fold increased cIAP-2 mRNA expression compared to the control subjects. Breast cancer patients in the TNM stages I, II, III, and IV showed 9.54, 11.80, 15.19, and 16.83 mean fold increased cIAP-1 mRNA expression (p=0.004). Distant organ metastasis, (p=0.008), PR status of breast cancer patients (p<0.0001), and HER2 status of breast cancer patients (p<0.0001) were found to be associated with cIAP-1 mRNA expression. Breast cancer patients with different TNM stages such as stages I, II, III, and IV showed 7.8, 8.09, 7.97, and 12.85 mean fold increased cIAP-2 mRNA expression (p=0.0002). Breast cancer patients with distant organ metastases status were found to be associated with cIAP-2 mRNA expression (p<0.0001). Breast cancer patients with <13-fold and >13-fold cIAP-1 mRNA expression showed 37.39 months and 34.70 months of overall median survival, and the difference among them was found to be significant (p=0.0001). However, cIAP-2 mRNA expression among <8-fold and >8-fold mRNA expression groups showed 35 months and 27.90 months of overall median survival time (p<0.0001). Higher cIAP-1 mRNA expression was linked with smoking and alcoholism among the breast cancer patients (p<0.0001 and p<0.0001). Significant association of higher cIAP-1 mRNA expression was found with the advancement of the disease, while higher mRNA expression of cIAP-1 was associated with distant organ metastases in ROC curve analysis. Conclusion. The present study suggested that increased cell-free cIAP-1 and cIAP-2 mRNA expression was correlated with the advancement of disease, progression of disease, and overall reduced patient survival. Cell-free cIAP-1 and cIAP-2 mRNA expression could be the predictive indicator of the disease.

Dual inhibitors of the human blood-brain barrier drug efflux transporters P-glycoprotein and ABCG2 based on the antiviral azidothymidine

2017 ◽  
Vol 25 (19) ◽  
pp. 5128-5132 ◽  
Author(s):  
Hilda A. Namanja-Magliano ◽  
Kelsey Bohn ◽  
Neha Agrawal ◽  
Meghan E. Willoughby ◽  
Christine A. Hrycyna ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Human Blood ◽  
Brain Barrier ◽  
Efflux Transporters ◽  
Drug Efflux ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Dual Inhibitors ◽  
Drug Efflux Transporters

scholarly journals P-glycoprotein Mediated Efflux Modulators of Plant Origin: A Short Review

2016 ◽  
Vol 11 (5) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Nuno Silva ◽  
Lígia Salgueiro ◽  
Ana Fortuna ◽  
Carlos Cavaleiro
Keyword(s):  
Short Review ◽  
Efflux Transporters ◽  
Drug Efflux ◽  
Plant Origin ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Plant Compounds ◽  
Drug Efflux Transporters

Drug efflux transporters such as P-glycoprotein (P-gp) help maintain cellular homeostasis but are also major contributors to the development of multidrug resistance (MDR) phenomena. Since P-gp was associated with MDR, several compounds showing potential to inhibit this transporter have been identified. Particular attention has been given to natural products, namely those of plant origin, looking for highly effective and safe P-gp inhibitors with little to no interaction with other cellular or metabolic processes. Here we abridge several examples of plant compounds from distinct classes, polyketides, lignans, anthraquinones, coumarins, alkaloids, mono- and sesqui-terpenes, steroids and limonoids, which have shown the ability to modulate in vitro or in vivo the P-gp activity.

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