Reduction of breast tumor drug resistance by 2,3,5,4’-tetrahydroxystilbene for exhibition synergic chemotherapeutic effect

Chemotherapy drugs have limited efficacy in breast cancer due to multidrug resistance generated by cancer cells against anticancer drugs. In this study, we developed a novel derivative, 2, 3, 5, 4‘-tetrahydroxystilbene (TG1) by modifying 2, 3, 5, 4‘-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG). In-vivo zebrafish embryo tests revealed that TG1 showed low toxicity. The equitoxic combination of DOX or DTX with TG1 in MCF-7/Adr reduced the IC50 of DOX or DTX, and the combination index (CI) showed strong synergistic effects in the 1:3 molar ratio of DTX: TG1 and 1:5 molar ratio of DOX: TG1. Moreover, fluorescence images confirmed the cellular uptake of DOX when combined with TG1 in MCF-7/Adr. Western blotting analysis indicated downregulation of p-glycoprotein (P-gp) after MCF-7/Adr treated with TG1. In conclusion, the combined therapy of DTX or DOX and TG1 increases drug efficacy via suppressing the p-glycoprotein efflux pump. These results suggest that TG1 may have potential use for breast cancer patients, especially those with multidrug resistance.

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Synergistic Effects of Lauryl Gallate and Tamoxifen on Human Breast Cancer Cell

Iranian Journal of Public Health ◽

10.18502/ijph.v49i7.3586 ◽

2020 ◽

Author(s):

Keihan GHATREH SAMANI ◽

Effat FARROKHI ◽

Aliye TABATABAEE ◽

Narges JALILIAN ◽

Mahbube JAFARI

Keyword(s):

Breast Cancer ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cell Apoptosis ◽

Synergistic Effects ◽

Medical Science ◽

Breast Cancer Patients ◽

Chemotherapy Drugs ◽

Lauryl Gallate ◽

Mcf 7

Background: Tamoxifen (TAM) is widely used for adjuvant therapy in breast cancer patients. Tamoxifen therapy may lead to serious side effects. Anti-apoptotic substances in combination with chemotherapy drugs can result in additive or synergistic effects. Lauryl gallate (LG), a Gallic acid derivative, has been proven to inhibit tumor growth, without affecting normal cells. This study aimed to investigate the synergistic effect of TAM and LG in breast cancer cell line (MCF-7). Methods: In this experimental study, performed in ShahreKord University of Medical Science, Iran in 2017, the MCF-7 cells were treated by final concentrations of 10 μM TAM alone, and in combination with 200 μM of LG. We also used EX-527, as SIRT-1 inhibitor to examine the role of SIRT1 in cell apoptosis. BCL-2 and SIRT1 gene expression were measured by real-time PCR method, and cell apoptosis was investigated by flow cytometry. Results: Tamoxifen alone and in combination with LG decreased BCL-2 expression 2.64±0.75 and 6.38±1.9 fold, respectively, after 48 h (P<0.05). SIRT1 expression was increased 1.67±0.22 and 2.47±0.34 - fold by TAM alone and in combination with LG, respectively (P<0.05). TAM alone and in combination with LG increased the percentage of apoptotic cells 15.79±2.81 and 60.67±6.23 percent, respectively after 48 h (P<0.001). Conclusion: The combination of LG and TAM is more effective for induction of apoptosis of breast cancer cells, compared to individual use of each. Thus, our data pave the way for new therapeutic options for suppressing breast cancer growth.

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Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells

Endocrine Related Cancer ◽

10.1677/erc-06-0016 ◽

2007 ◽

Vol 14 (2) ◽

pp. 293-303 ◽

Cited By ~ 50

Author(s):

Hoo Kyun Choi ◽

Jin Won Yang ◽

Sang Hee Roh ◽

Chang Yeob Han ◽

Keon Wook Kang

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

Cancer Cells ◽

Transcriptional Activation ◽

Breast Cancer Cells ◽

Pregnane X Receptor ◽

Pi3 Kinase ◽

Gene Promoters ◽

Breast Cancer Patients ◽

Mcf 7

Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. The transition from chemotherapy-responsive breast cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multidrug resistance-associated proteins (MRPs). In this study, it was found that TAM-resistant MCF-7 (TAMR-MCF-7) cells expressed higher levels of MRP2 than control MCF-7 cells. Molecular analyses using MRP2 gene promoters supported the involvement of the pregnane X receptor (PXR) in MRP2 overexpression in TAMR-MCF-7 cells. Although CCAAT/enhancer-binding protein β was overexpressed continuously in TAMR-MCF-7 cells, this might not be responsible for the transcriptional activation of the MRP2 gene. In addition, the basal activities of phosphatidylinositol 3-kinase (PI3-kinase) were higher in the TAMR-MCF-7 cells than in the control cells. The inhibition of PI3-kinase significantly reduced both the PXR activity and MRP2 expression in TAMR-MCF-7 cells. Overall, MRP2 induction plays a role in the additional acquisition of chemotherapy resistance in TAM-resistant breast cancer.

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Psoralen reverses the P-glycoprotein-mediated multidrug resistance in human breast cancer MCF-7/ADR cells

Molecular Medicine Reports ◽

10.3892/mmr.2016.5098 ◽

2016 ◽

Vol 13 (6) ◽

pp. 4745-4750 ◽

Cited By ~ 18

Author(s):

JINGRU JIANG ◽

XIAOHONG WANG ◽

KAI CHENG ◽

WANZHONG ZHAO ◽

YITONG HUA ◽

...

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

Human Breast Cancer ◽

Human Breast ◽

P Glycoprotein ◽

Mcf 7

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Reversal of P-glycoprotein-mediated multidrug resistance is induced by saikosaponin D in breast cancer MCF-7/adriamycin cells

Pathology - Research and Practice ◽

10.1016/j.prp.2017.01.022 ◽

2017 ◽

Vol 213 (7) ◽

pp. 848-853 ◽

Cited By ~ 9

Author(s):

Chun Li ◽

Xingang Guan ◽

Haogang Xue ◽

Peng Wang ◽

Manli Wang ◽

...

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

P Glycoprotein ◽

Mcf 7

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Survivin transcription is associated with P-glycoprotein/MDR1 overexpression in the multidrug resistance of MCF-7 breast cancer cells

Oncology Reports ◽

10.3892/or_00000786 ◽

2010 ◽

Vol 23 (5) ◽

Cited By ~ 12

Author(s):

Jiang

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

Cancer Cells ◽

Breast Cancer Cells ◽

P Glycoprotein ◽

Mcf 7

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Diltiazem potentiation of doxorubicin cytotoxicity and cellular uptake in human breast cancer cells

Breast Cancer Management ◽

10.2217/bmt-2019-0018 ◽

2019 ◽

Vol 8 (4) ◽

pp. BMT31

Author(s):

Hamdan S Al-malky ◽

Zoheir A Damanhouri ◽

Jumana Y Al Aama ◽

Ali A Al Qahtani ◽

Wafaa S Ramadan ◽

...

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

Cytotoxic Activity ◽

Cellular Uptake ◽

Breast Cancer Cells ◽

Limiting Factors ◽

Human Breast ◽

Common Cancer ◽

P Glycoprotein ◽

Mcf 7

Aim: Breast cancer is the most common cancer among Arab women and also around the world. Chronic cardiotoxicity and multidrug resistance are potential limiting factors of doxorubicin (DOX), a known anthracycline antibiotic. Materials & methods: DOX cytotoxicity was evaluated by the sulforhodamine method. DOX cellular uptake, detection of P-glycoprotein activity and the photomicrograph of MCF-7 cells were also determined. Results: Diltiazem (DIL) treatment improved DOX cytotoxic activity and increased the cellular uptake of DOX significantly and aggregation of rhodamine 123, reflecting inhibition of P-glycoprotein pump. Cytopathological investigation of MCF-7 cells revealed marked cytotoxic activity of DOX in the presence of DIL. Conclusion: DIL treatment enhanced DOX cytotoxic effect and reduced multidrug resistance, which increased the drug accumulation intracellularly.

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Hesperidin and Chlorogenic Acid Synergistically Inhibit the Growth of Breast Cancer Cells via Estrogen Receptor/Mitochondrial Pathway

Life ◽

10.3390/life11090950 ◽

2021 ◽

Vol 11 (9) ◽

pp. 950

Author(s):

Pang-Hung Hsu ◽

Wei-Hsuan Chen ◽

Chen JuanLu ◽

Shu-Chen Hsieh ◽

Shih-Chao Lin ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Chlorogenic Acid ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Breast Cancer Patients ◽

Atp Production ◽

Chemotherapy Drugs ◽

Mitochondrial Functions ◽

Mcf 7

Breast cancer is the most common cancer in women worldwide. Hesperidin (Hes) and chlorogenic acid (CA) are traditional medicinal molecules that abundantly exist in natural plants or foods. These compounds have been shown to prevent and suppress various cancers and therefore can be utilized as adjunctive therapies to aid cancer treatment. Here, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays show a greater synergistic inhibitory effect on the growth of breast cancer cells, MCF-7, but not normal breast cells, MCF-10A, than hesperidin or chlorogenic acid alone. We present the possible molecular signaling pathways in MCF-7 cells with or without herbal molecule treatments via proteomic approaches. The data were further analyzed by Ingenuity Pathway Analysis (IPA) and confirmed by quantifying mRNA associated with the estrogen-receptor signaling pathway and mitochondrial functions. We demonstrated that the expression of CYC1, TFAM, ATP5PB, mtATP6, mtDNA, and NRF-1 were decreased upon 12 h treatment, and subsequent ATP production was also significantly decreased at 24 h. These results identified a synergistic effect induced by combinational treatment with hesperidin and chlorogenic acid, which can regulate mitochondria and ATP production through the estrogen receptor pathway in MCF-7 cells. However, none of the treatments induced the generation of reactive oxygen species (ROS), suggesting that ROS likely plays no role in the observed pharmacological activities. Overall, our study sheds light on the adequacy of hesperidin and chlorogenic acid to serve as an adjunctive therapy when co-administrated with chemotherapy drugs in breast cancer patients.

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Co-delivery of doxorubicin and the traditional Chinese medicine quercetin using biotin–PEG2000–DSPE modified liposomes for the treatment of multidrug resistant breast cancer

RSC Advances ◽

10.1039/c6ra24173e ◽

2016 ◽

Vol 6 (114) ◽

pp. 113173-113184 ◽

Cited By ~ 9

Author(s):

Jiulong Zhang ◽

Yue Luo ◽

Xiufeng Zhao ◽

Xiaowei Li ◽

Kexin Li ◽

...

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

Chinese Medicine ◽

Cancer Therapy ◽

Traditional Chinese Medicine ◽

Efflux Pump ◽

Multidrug Resistant ◽

Glycoprotein P ◽

P Glycoprotein

At present, multidrug resistance (MDR) in cancer therapy is an international problem, which is caused mostly by the overexpressed P-glycoprotein (P-gp) efflux pump.

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