Quercetin Synergistically Enhances the Anticancer Efficacy of Docetaxel through Induction of Apoptosis and Modulation of PI3K/AKT, MAPK/ERK, and JAK/STAT3 Signaling Pathways in MDA-MB-231 Breast Cancer Cell Line

Authors

  • Amir Safi Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
  • Esfandiar Heidarian Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
  • Reza Ahmadi Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Abstract:

Docetaxel is widely used in the treatment of metastatic breast cancer. However, its effectiveness is limited due to chemoresistance and its undesirable side effects. The combination of chemotherapeutic agents and natural compounds is an effective strategy to overcome drug resistance and the ensuing inevitable toxicities. Quercetin is a natural flavonoid with strong antioxidant and anticancer activities. This study aimed to evaluate the cytotoxic and modulatory effects of combined docetaxel and quercetin on the MDA-MB-231 human breast cancer cell line. The cell viability was assessed by MTT assay. The induction of apoptosis was examined using flow cytometry. The role of p53 in the apoptotic process was evaluated via qRT-PCR. The levels of BAX, BCL2, ERK1/2, AKT, and STAT3 proteins were measured by Western blot analysis. The results showed that the single-agent treatment with docetaxel or quercetin leads to a decrease in the viability of the MDA-MB-231 cells at 48 h. Furthermore, the combination of docetaxel (7 nM) and quercetin (95 μM) displayed the greatest synergistic effects with a combination index value of 0.76 accompanied by up regulation of p53 and a significant increase in BAX level, as well as decreases in the levels of BCL2, pERK1/2, AKT, and STAT3 proteins (P < 0.05). The concomitant use of docetaxel and quercetin leads to the cell growth inhibition associated with the induction of apoptosis and inhibition of cell survival. Therefore, this study provides a promising therapeutic approach to enhance the efficacy of docetaxel in a less-toxic manner.

Upgrade to premium to download articles

Sign up to access the full text

Already have an account?login

similar resources

the study of aaag repeat polymorphism in promoter of errg gene and its association with the risk of breast cancer in isfahan region

چکیده: سرطان پستان دومین عامل مرگ مرتبط با سرطان در خانم ها است. از آنجا که سرطان پستان یک تومور وابسته به هورمون است، می تواند توسط وضعیت هورمون های استروئیدی شامل استروژن و پروژسترون تنظیم شود. استروژن نقش مهمی در توسعه و پیشرفت سرطان پستان ایفا می کند و تاثیر خود را روی بیان ژن های هدف از طریق گیرنده های استروژن اعمال می کند. اما گروه دیگری از گیرنده های هسته ای به نام گیرنده های مرتبط به ا...

15 صفحه اول

Intermittent low dose irradiation enhances the effectiveness of radio-therapy for human breast adenocarcinoma cell line MDA–MB–231

Introduction: Hormesis and adaptive responses are two important biological effects of low-dose ionizing radiation (LDIR) in organism and mammalian cell lines. Notably, LDIR generates distinct biological effects in cancer cells from normal cells, e.g., it may affect the growth of cancer cells via the activation of certain cell signaling pathway, which does not exist in normal ...

full text

Transcriptional effects of metal ions on the bovine oxytocin and the thymidine kinase-ERE promoter through the estrogen receptor a in MDA-MB 231 breast cancer cell line

BACKGROUND: Some of metal ions as environmental pollutants show estrogenic activity. This xenostrogenic compounds can be caused carcinogenicity in organs. The mechanism of carcinogenicity of metal ions is not clarified. OBJECTIVES: In this study, we investigated the Transcriptional effects of variety of metal ions on the bovine oxytocin and the thymidine kinase-ERE promoter by estrogen receptor...

full text

THE EFFECT OF QUINACRINE ON THE EXPRESSION OF WNT3A GENE IN MDA-MB 231 AND MCF7 BREAST CANCER CELL LINES

Background & Aims: Triple-negative breast cancer cells refer to any breast cancer that does not express the genes for the estrogen, progesterone, and HER2 receptors. The Wnt signaling pathway is important in the development and progression of various types of cancers. Quinacrine, a derivative of 9-aminoacridine, has been shown to inhibit the growth of several types of cancer cells. In this stud...

full text

Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin

Objective(s):The colorectal cancer stem cells (CSCs) with the CD133+ phenotype are a rare fraction of cancer cells with the ability of self-renewal, unlimited proliferation and resistance to treatment. Quercetin has anticancer effects with the advantage of exhibiting low side effects. Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT29 cancer cells and its ...

full text

Apoptosis Induced by 13-S-hydroxyoctadecadienoic acid in the Breast Cancer Cell Lines, MCF-7 and MDA-MB-231

full text

My Resources

Save resource for easier access later

Save to my library Already added to my library

{@ msg_add @}


Journal title

volume 10  issue 1

pages  0- 0

publication date 2021-01

{@ msg @}

By following a journal you will be notified via email when a new issue of this journal is published.

Keywords

Hosted on Doprax cloud platform doprax.com

copyright © 2015-2023