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

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.

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

Advances in Pharmacological Sciences ◽

10.1155/2016/6702424 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 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.

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

Medical Journal of Indonesia ◽

10.13181/mji.v28i2.2687 ◽

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.

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Apigenin by targeting hnRNPA2 sensitizes triple-negative breast cancer spheroids to doxorubicin-induced apoptosis and regulates expression of ABCC4 and ABCG2 drug efflux transporters

Biochemical Pharmacology ◽

10.1016/j.bcp.2020.114259 ◽

2020 ◽

Vol 182 ◽

pp. 114259

Author(s):

Meenakshi Sudhakaran ◽

Michael Ramirez Parra ◽

Hayden Stoub ◽

Kathleen A. Gallo ◽

Andrea I. Doseff

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Efflux Transporters ◽

Drug Efflux ◽

Induced Apoptosis ◽

Cancer Spheroids ◽

Drug Efflux Transporters

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Faculty Opinions recommendation of Torin2 Exploits Replication and Checkpoint Vulnerabilities to Cause Death of PI3K-Activated Triple-Negative Breast Cancer Cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737060005.793568589 ◽

2019 ◽

Author(s):

Junjie Chen

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative

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MiRNAs-181a/b as Predictive biomarkers for olaparib sensitivity in triple-negative breast cancer cells.

Biochemistry Letters ◽

10.21608/blj.2017.47612 ◽

2017 ◽

Vol 12 (1) ◽

pp. 221-229

Author(s):

Abeer M. Ashmawy ◽

Mona A. Sheta ◽

Faten Zahran ◽

Abdel Hady A. Abdel Wahab

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Predictive Biomarkers

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

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018.v10s1.21 ◽

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.

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