Multiple Drug Resistance in Breast Cancer Cells: Mirnaome Dysregulation can Facilitate Expression of Genes Encoding the ATP Binding Cassette (ABC) Transporters

Paclitaxel (Tx) is a widely used therapeutic chemical for breast cancer treatment; however, cancer recurrence remains an obstacle for improved prognosis of cancer patients. In this study, cold atmospheric plasma (CAP) was tested for its potential to overcome the drug resistance. After developing Tx-resistant MCF-7 (MCF-7/TxR) breast cancer cells, CAP was applied to the cells, and its effect on the recovery of drug sensitivity was assessed in both cellular and molecular aspects. Sensitivity to Tx in the MCF-7/TxR cells was restored up to 73% by CAP. A comparison of genome-wide expression profiles between the TxR cells and the CAP-treated cells identified 49 genes that commonly appeared with significant changes. Notably, 20 genes, such as KIF13B, GOLM1, and TLE4, showed opposite expression profiles. The protein expression levels of selected genes, DAGLA and CEACAM1, were recovered to those of their parental cells by CAP. Taken together, CAP inhibited the growth of MCF-7/TxR cancer cells and recovered Tx sensitivity by resetting the expression of multiple drug resistance–related genes. These findings may contribute to extending the application of CAP to the treatment of TxR cancer.

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Nelfinavir targets multiple drug resistance mechanisms to increase the efficacy of doxorubicin in MCF-7/Dox breast cancer cells

Biochimie ◽

10.1016/j.biochi.2016.01.014 ◽

2016 ◽

Vol 124 ◽

pp. 53-64 ◽

Cited By ~ 22

Author(s):

Geetika Chakravarty ◽

Aditi Mathur ◽

Pallavi Mallade ◽

Samantha Gerlach ◽

Joniece Willis ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Multiple Drug Resistance ◽

Resistance Mechanisms ◽

Multiple Drug ◽

Mcf 7

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Flavonoids overcome drug resistance to cancer chemotherapy by epigenetically modulating multiple mechanisms

Current Cancer Drug Targets ◽

10.2174/1568009621666210203111220 ◽

2021 ◽

Vol 21 ◽

Author(s):

Kenneth K.W. To ◽

William C.S. Cho

Keyword(s):

Drug Resistance ◽

Cancer Cells ◽

Cancer Chemotherapy ◽

Animal Studies ◽

Multiple Drug Resistance ◽

Resistance Mechanisms ◽

Multiple Drug ◽

Full Potential ◽

Cancer Proliferation ◽

Genes Encoding

Drug resistance is the major reason accounting for the treatment failure in cancer chemotherapy. Dysregulation of the epigenetic machineries is known to induce chemoresistance. It was reported that numerous genes encoding the key mediators in cancer proliferation, apoptosis, DNA repair, and drug efflux are dysregulated in resistant cancer cells by aberrant DNA methylation. The imbalance of various enzymes catalyzing histone post-translational modifications is also known to alter chromatin configuration and regulate multiple drug resistance genes. Alteration in miRNA signature in cancer cells also gives rise to chemoresistance. Flavonoids are a large group of naturally occurring polyphenolic compounds ubiquitously found in plants, fruits, vegetables and traditional herbs. There has been an increasing research interest in the health-promoting effects of flavonoids. Flavonoids were shown to directly kill or re-sensitize resistant cancer cells to conventional anticancer drugs by epigenetic mechanisms. In this review, we summarize the current findings about the circumvention of drug resistance by flavonoids through correcting the aberrant epigenetic regulation of multiple resistance mechanisms. More investigations including the evaluation of synergistic anticancer activity, dosing sequence effect, toxicity in normal cells, and animal studies, are warranted to establish the full potential of the combination of flavonoids with conventional chemotherapeutic drugs in the treatment of cancer with drug resistance.

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Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells

International Journal of Oncology ◽

10.3892/ijo.2014.2389 ◽

2014 ◽

Vol 45 (1) ◽

pp. 448-458 ◽

Cited By ~ 11

Author(s):

SIYING CHEN ◽

JIANGXIA CAI ◽

WEIPENG ZHANG ◽

XIAOWEI ZHENG ◽

SASA HU ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Multiple Drug Resistance ◽

Multiple Drug ◽

Differentially Expressed Proteins ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Proteomic Identification

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The Long-Term DEHP Exposure Confers Multidrug Resistance of Triple-Negative Breast Cancer Cells through ABC Transporters and Intracellular ROS

Antioxidants ◽

10.3390/antiox10060949 ◽

2021 ◽

Vol 10 (6) ◽

pp. 949

Author(s):

Mahendra Jadhao ◽

Eing-Mei Tsai ◽

Ho-Chun Yang ◽

Yih-Fung Chen ◽

Shih-Shin Liang ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Multidrug Resistance ◽

Cancer Cells ◽

Abc Transporters ◽

Breast Cancer Cells ◽

Acquired Drug Resistance ◽

Intracellular Ros ◽

Dehp Exposure

The characteristics of phthalates had been thought to be similar to endocrine disruptors, which increases cancer risk. The role of phthalates in acquired drug resistance remains unclear. In this study, we investigated the effect of di-(2-ethylhexyl) phthalate (DEHP) on acquired drug resistance in breast cancer. MCF7 and MDA-MB-231 breast cancer cells were exposed to long-term physiological concentration of DEHP for more than three months. Long-exposure DEHP permanently attenuated the anti-proliferative effect of doxorubicin with estrogen receptor-independent activity even after withdrawal of DEHP. Long term DEHP exposure significantly reduced ROS (O2−) level in MDA-MB-231 cells while increased in MCF7 cells. ATP-binding cassette (ABC) transporters possess a widely recognized mechanism of drug resistance and are considered a target for drug therapy. Upregulation of ABC family proteins, ABCB-1 and ABCC-1 observed in DEHP-exposed clones compared to doxorubicin-resistant (DoxR) and parental MDA-MB-231 cells. A viability assay showed enhanced multidrug resistance in DEHP-exposed clones against Dox, topotecan, and irinotecan. Inhibition of ABC transporters with tariquidar, enhanced drug cytotoxicity through increased drug accumulation reversing acquired multidrug resistance in MDA-MB-231 breast cancer cells. Tariquidar enhanced Dox cytotoxicity by increasing intracellular ROS production leading to caspase-3 mediated apoptosis. Activation of PI3K/Akt signaling enhanced proliferation and growth of DEHP-exposed MDA-MB-231 cells. Overall, long-term DEHP exposure resulted in acquired multidrug resistance by upregulating ABCB-1 and ABCC1; apart from proliferation PI3K/Akt may be responsible for acquired drug resistance through ABC transporter upregulation. Targeting ABCB1 and ABCC1 with tariquidar may be a promising strategy for reversing the acquired multidrug resistance of triple-negative breast cancer cells.

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Clinically-Relevant ABC Transporter for Anti-Cancer Drug Resistance

Frontiers in Pharmacology ◽

10.3389/fphar.2021.648407 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huan Xiao ◽

Yongcheng Zheng ◽

Lingling Ma ◽

Lili Tian ◽

Qiu Sun

Keyword(s):

Drug Resistance ◽

Cancer Cells ◽

Abc Transporter ◽

Abc Transporters ◽

Multiple Drug Resistance ◽

Cancer Drug ◽

Multiple Drug ◽

Cancer Drug Resistance ◽

Response To Chemotherapy ◽

New Compounds

Multiple drug resistance (MDR), referring to the resistance of cancer cells to a broad spectrum of structurally and mechanistically unrelated drugs across membranes, severely impairs the response to chemotherapy and leads to chemotherapy failure. Overexpression of ATP binding cassette (ABC) transporters is a major contributing factor resulting in MDR, which can recognize and mediate the efflux of diverse drugs from cancer cells, thereby decreasing intracellular drug concentration. Therefore, modulators of ABC transporter could be used in combination with standard chemotherapeutic anticancer drugs to augment the therapeutic efficacy. This review summarizes the recent advances of important cancer-related ABC transporters, focusing on their physiological functions, structures, and the development of new compounds as ABC transporter inhibitors.

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