All-trans retinoic acids induce differentiation and sensitize a radioresistant breast cancer cells to chemotherapy

Yunwen Yan, Zhen Li, Xiang Xu, Clark Chen, Wei Wei, Ming Fan, Xufeng Chen, Jian-Jian Li, Yuan Wang, Jiaoti Huang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Radiotherapy is of critical importance in the treatment of breast cancer. However, not all patients derive therapeutic benefit and some breast cancers are resistant to the treatment, and are thus evidenced with prospective distant metastatic spread and local recurrence. In this study, we investigated the potential therapeutic effects of all-trans retinoic acid (ATRA) on radiation-resistant breast cancer cells and the associated invasiveness. Methods: The MCF7/C6 cells with gained radiation resistance after a long term treatment with fractionated ionizing radiation were derived from human breast cancer MCF7 cell line, and are enriched with cells expressing putative breast cancer stem cell biomarker CD44+/CD24-/low/ALDH+. The enhanced invasiveness and the acquired resistances to chemotherapeutic treatments of MCF7/C6 cells were measured, and potential effects of all-trans retinoic acid (ATRA) on the induction of differentiation, invasion and migration, and on the sensitivities to chemotherapies in MCF7/C6 cells were investigated. Results: MCF7/C6 cells are with enrichment of cancer stem-cell like cells with positive staining of CD44+/CD24-/low, OCT3/4 and NANOG. MCF7/C6 cells showed an increased tumoregensis potential and enhanced aggressiveness of invasion and migration. Treatment with ATRA induces the differentiation in MCF7/C6 cells, resulting in reduced invasiveness and migration, and increased sensitivity to Epirubincin treatment. Conclusion: Our study suggests a potential clinic impact for ATRA as a chemotherapeutic agent for treatment of therapy-resistant breast cancer especially for the metastatic lesions. The study also provides a rationale for ATRA as a sensitizer of Epirubincin, a first-line treatment option for breast cancer patients.

Original languageEnglish (US)
Article number113
JournalBMC Complementary and Alternative Medicine
Volume16
Issue number1
DOIs
StatePublished - 2016

Fingerprint

Tretinoin
MCF-7 Cells
Breast Neoplasms
Drug Therapy
Therapeutics
Neoplastic Stem Cells
Radiation
Therapeutic Uses
Ionizing Radiation
Radiotherapy
Biomarkers
Staining and Labeling
Recurrence
Cell Line

Keywords

  • ATRA
  • Breast cancer
  • Cancer stem cell
  • Radiation resistance

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

All-trans retinoic acids induce differentiation and sensitize a radioresistant breast cancer cells to chemotherapy. / Yan, Yunwen; Li, Zhen; Xu, Xiang; Chen, Clark; Wei, Wei; Fan, Ming; Chen, Xufeng; Li, Jian-Jian; Wang, Yuan; Huang, Jiaoti.

In: BMC Complementary and Alternative Medicine, Vol. 16, No. 1, 113, 2016.

Research output: Contribution to journalArticle

Yan, Yunwen ; Li, Zhen ; Xu, Xiang ; Chen, Clark ; Wei, Wei ; Fan, Ming ; Chen, Xufeng ; Li, Jian-Jian ; Wang, Yuan ; Huang, Jiaoti. / All-trans retinoic acids induce differentiation and sensitize a radioresistant breast cancer cells to chemotherapy. In: BMC Complementary and Alternative Medicine. 2016 ; Vol. 16, No. 1.
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AU - Yan, Yunwen

AU - Li, Zhen

AU - Xu, Xiang

AU - Chen, Clark

AU - Wei, Wei

AU - Fan, Ming

AU - Chen, Xufeng

AU - Li, Jian-Jian

AU - Wang, Yuan

AU - Huang, Jiaoti

PY - 2016

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N2 - Background: Radiotherapy is of critical importance in the treatment of breast cancer. However, not all patients derive therapeutic benefit and some breast cancers are resistant to the treatment, and are thus evidenced with prospective distant metastatic spread and local recurrence. In this study, we investigated the potential therapeutic effects of all-trans retinoic acid (ATRA) on radiation-resistant breast cancer cells and the associated invasiveness. Methods: The MCF7/C6 cells with gained radiation resistance after a long term treatment with fractionated ionizing radiation were derived from human breast cancer MCF7 cell line, and are enriched with cells expressing putative breast cancer stem cell biomarker CD44+/CD24-/low/ALDH+. The enhanced invasiveness and the acquired resistances to chemotherapeutic treatments of MCF7/C6 cells were measured, and potential effects of all-trans retinoic acid (ATRA) on the induction of differentiation, invasion and migration, and on the sensitivities to chemotherapies in MCF7/C6 cells were investigated. Results: MCF7/C6 cells are with enrichment of cancer stem-cell like cells with positive staining of CD44+/CD24-/low, OCT3/4 and NANOG. MCF7/C6 cells showed an increased tumoregensis potential and enhanced aggressiveness of invasion and migration. Treatment with ATRA induces the differentiation in MCF7/C6 cells, resulting in reduced invasiveness and migration, and increased sensitivity to Epirubincin treatment. Conclusion: Our study suggests a potential clinic impact for ATRA as a chemotherapeutic agent for treatment of therapy-resistant breast cancer especially for the metastatic lesions. The study also provides a rationale for ATRA as a sensitizer of Epirubincin, a first-line treatment option for breast cancer patients.

AB - Background: Radiotherapy is of critical importance in the treatment of breast cancer. However, not all patients derive therapeutic benefit and some breast cancers are resistant to the treatment, and are thus evidenced with prospective distant metastatic spread and local recurrence. In this study, we investigated the potential therapeutic effects of all-trans retinoic acid (ATRA) on radiation-resistant breast cancer cells and the associated invasiveness. Methods: The MCF7/C6 cells with gained radiation resistance after a long term treatment with fractionated ionizing radiation were derived from human breast cancer MCF7 cell line, and are enriched with cells expressing putative breast cancer stem cell biomarker CD44+/CD24-/low/ALDH+. The enhanced invasiveness and the acquired resistances to chemotherapeutic treatments of MCF7/C6 cells were measured, and potential effects of all-trans retinoic acid (ATRA) on the induction of differentiation, invasion and migration, and on the sensitivities to chemotherapies in MCF7/C6 cells were investigated. Results: MCF7/C6 cells are with enrichment of cancer stem-cell like cells with positive staining of CD44+/CD24-/low, OCT3/4 and NANOG. MCF7/C6 cells showed an increased tumoregensis potential and enhanced aggressiveness of invasion and migration. Treatment with ATRA induces the differentiation in MCF7/C6 cells, resulting in reduced invasiveness and migration, and increased sensitivity to Epirubincin treatment. Conclusion: Our study suggests a potential clinic impact for ATRA as a chemotherapeutic agent for treatment of therapy-resistant breast cancer especially for the metastatic lesions. The study also provides a rationale for ATRA as a sensitizer of Epirubincin, a first-line treatment option for breast cancer patients.

KW - ATRA

KW - Breast cancer

KW - Cancer stem cell

KW - Radiation resistance

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