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Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin.
Biochim Biophys Acta. 2014 Jan; 1840(1):615-25.BB

Abstract

BACKGROUND

Multidrug resistance is a major problem in the treatment of breast cancer, and a number of studies have attempted to find an efficient strategy with which to overcome it. In this study, we investigate the synergistic anticancer effects of resveratrol (RSV) and doxorubicin (Dox) against human breast cancer cell lines.

METHODS

The synergistic effects of RSV on chemosensitivity were examined in Dox-resistant breast cancer (MCF-7/adr) and MDA-MB-231 cells. In vivo experiments were performed using a nude mouse xenograft model to investigate the combined sensitization effect of RSV and Dox.

RESULTS AND CONCLUSION

RSV markedly enhanced Dox-induced cytotoxicity in MCF-7/adr and MDA-MB-231 cells. Treatment with a combination of RSV and Dox significantly increased the cellular accumulation of Dox by down-regulating the expression levels of ATP-binding cassette (ABC) transporter genes, MDR1, and MRP1. Further in vivo experiments in the xenograft model revealed that treatment with a combination of RSV and Dox significantly inhibited tumor volume by 60%, relative to the control group.

GENERAL SIGNIFICANCE

These results suggest that treatment with a combination of RSV and Dox would be a helpful strategy for increasing the efficacy of Dox by promoting an intracellular accumulation of Dox and decreasing multi-drug resistance in human breast cancer cells.

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Authors+Show Affiliations

Kim TH
Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, Busan 609-735, Republic of Korea; Division of Toxicology, College of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
Shin YJ
No affiliation info available
Won AJ
No affiliation info available
Lee BM
No affiliation info available
Choi WS
No affiliation info available
Jung JH
No affiliation info available
Chung HY
No affiliation info available
Kim HS
No affiliation info available

MeSH

ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1AnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBlotting, WesternBreast NeoplasmsCell ProliferationDoxorubicinDrug Resistance, MultipleDrug Resistance, NeoplasmDrug SynergismFemaleHumansMiceMice, Inbred BALB CMultidrug Resistance-Associated ProteinsRNA, MessengerReal-Time Polymerase Chain ReactionResveratrolReverse Transcriptase Polymerase Chain ReactionStilbenesTissue DistributionTumor Cells, Cultured

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24161697

Citation

Kim, Tae Hyung, et al. "Resveratrol Enhances Chemosensitivity of Doxorubicin in Multidrug-resistant Human Breast Cancer Cells Via Increased Cellular Influx of Doxorubicin." Biochimica Et Biophysica Acta, vol. 1840, no. 1, 2014, pp. 615-25.
Kim TH, Shin YJ, Won AJ, et al. Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin. Biochim Biophys Acta. 2014;1840(1):615-25.
Kim, T. H., Shin, Y. J., Won, A. J., Lee, B. M., Choi, W. S., Jung, J. H., Chung, H. Y., & Kim, H. S. (2014). Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin. Biochimica Et Biophysica Acta, 1840(1), 615-25. https://doi.org/10.1016/j.bbagen.2013.10.023
Kim TH, et al. Resveratrol Enhances Chemosensitivity of Doxorubicin in Multidrug-resistant Human Breast Cancer Cells Via Increased Cellular Influx of Doxorubicin. Biochim Biophys Acta. 2014;1840(1):615-25. PubMed PMID: 24161697.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin. AU - Kim,Tae Hyung, AU - Shin,Yu Jin, AU - Won,A Jin, AU - Lee,Byung Mu, AU - Choi,Wahn Soo, AU - Jung,Jee H, AU - Chung,Hae Young, AU - Kim,Hyung Sik, Y1 - 2013/10/24/ PY - 2013/03/15/received PY - 2013/10/13/revised PY - 2013/10/15/accepted PY - 2013/10/29/entrez PY - 2013/10/29/pubmed PY - 2014/3/14/medline KW - ABC transporter KW - ATP-binding cassette transporter KW - Breast cancer KW - DMEM KW - DMSO KW - Dimethylsulfoxide KW - Dox KW - Doxorubicin KW - Doxorubicin-resistant MCF-7 KW - Drug-resistant KW - Dulbecco's Modified Eagle Medium KW - MCF-7/adr KW - MDR KW - MRP KW - Multi-drug resistance KW - Multi-drug resistance associated protein KW - P-glycoprotein KW - P-gp KW - RSV KW - RT-PCR KW - Resveratrol KW - Reverse transcription polymerase chain reaction KW - TUNEL KW - Terminal deoxynuclotidyl transferase dUTP nick end labeling SP - 615 EP - 25 JF - Biochimica et biophysica acta JO - Biochim. Biophys. Acta VL - 1840 IS - 1 N2 - BACKGROUND: Multidrug resistance is a major problem in the treatment of breast cancer, and a number of studies have attempted to find an efficient strategy with which to overcome it. In this study, we investigate the synergistic anticancer effects of resveratrol (RSV) and doxorubicin (Dox) against human breast cancer cell lines. METHODS: The synergistic effects of RSV on chemosensitivity were examined in Dox-resistant breast cancer (MCF-7/adr) and MDA-MB-231 cells. In vivo experiments were performed using a nude mouse xenograft model to investigate the combined sensitization effect of RSV and Dox. RESULTS AND CONCLUSION: RSV markedly enhanced Dox-induced cytotoxicity in MCF-7/adr and MDA-MB-231 cells. Treatment with a combination of RSV and Dox significantly increased the cellular accumulation of Dox by down-regulating the expression levels of ATP-binding cassette (ABC) transporter genes, MDR1, and MRP1. Further in vivo experiments in the xenograft model revealed that treatment with a combination of RSV and Dox significantly inhibited tumor volume by 60%, relative to the control group. GENERAL SIGNIFICANCE: These results suggest that treatment with a combination of RSV and Dox would be a helpful strategy for increasing the efficacy of Dox by promoting an intracellular accumulation of Dox and decreasing multi-drug resistance in human breast cancer cells. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/24161697/Resveratrol_enhances_chemosensitivity_of_doxorubicin_in_multidrug_resistant_human_breast_cancer_cells_via_increased_cellular_influx_of_doxorubicin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-4165(13)00463-7 DB - PRIME DP - Unbound Medicine ER -