BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo

Shujie Cheng, Victor Castillo, Matt Welty, Mark Alvarado, Isaac Eliaz, Constance J. Temm, George Sandusky, Daniel Sliva

Research output: Contribution to journalArticle

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Abstract

Background: Tamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer. Methods: Cell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively. The molecular mechanism was identified using RNA microarray analysis and western blotting. Tumor tissues from xenograft mouse model were analyzed by immunohistochemistry. Results: Our data clearly demonstrate that a combination of 4-hydroxytamoxifen (4-OHT) with BD lead to profound inhibition of cell proliferation and induction of apoptosis in MCF-7 cells. This effect is consistent with the regulation of apoptotic and TAM resistant genes at the transcription and translation levels. Importantly, TAM and BD co-treatment significantly enhanced apoptosis, suppressed tumor growth and reduced tumor weight in a xenograft model of human ER-positive breast cancer. Conclusion: BD sensitized ER-positive human breast cancer cells to 4-OHT/TAM treatment in vitro and in vivo. BreastDefend can be used in an adjuvant therapy to increase the therapeutic effect of tamoxifen in patients with ER-positive breast cancer.

Original languageEnglish (US)
Article number115
JournalBMC Complementary and Alternative Medicine
Volume17
Issue number1
DOIs
StatePublished - Feb 16 2017

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Tamoxifen
Estrogen Receptors
Breast Neoplasms
MCF-7 Cells
Apoptosis
Heterografts
Therapeutics
Cell Proliferation
Therapeutic Uses
Microarray Analysis
Dietary Supplements
In Vitro Techniques
Tumor Burden
Histones
Neoplasms
Western Blotting
Immunohistochemistry
RNA
DNA
Growth

Keywords

  • Apoptosis
  • BreastDefend
  • Estrogen receptor
  • MCF-7
  • Polybotanical supplement
  • Tamoxifen
  • Xenograft model

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo. / Cheng, Shujie; Castillo, Victor; Welty, Matt; Alvarado, Mark; Eliaz, Isaac; Temm, Constance J.; Sandusky, George; Sliva, Daniel.

In: BMC Complementary and Alternative Medicine, Vol. 17, No. 1, 115, 16.02.2017.

Research output: Contribution to journalArticle

Cheng, Shujie ; Castillo, Victor ; Welty, Matt ; Alvarado, Mark ; Eliaz, Isaac ; Temm, Constance J. ; Sandusky, George ; Sliva, Daniel. / BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo. In: BMC Complementary and Alternative Medicine. 2017 ; Vol. 17, No. 1.
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abstract = "Background: Tamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer. Methods: Cell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively. The molecular mechanism was identified using RNA microarray analysis and western blotting. Tumor tissues from xenograft mouse model were analyzed by immunohistochemistry. Results: Our data clearly demonstrate that a combination of 4-hydroxytamoxifen (4-OHT) with BD lead to profound inhibition of cell proliferation and induction of apoptosis in MCF-7 cells. This effect is consistent with the regulation of apoptotic and TAM resistant genes at the transcription and translation levels. Importantly, TAM and BD co-treatment significantly enhanced apoptosis, suppressed tumor growth and reduced tumor weight in a xenograft model of human ER-positive breast cancer. Conclusion: BD sensitized ER-positive human breast cancer cells to 4-OHT/TAM treatment in vitro and in vivo. BreastDefend can be used in an adjuvant therapy to increase the therapeutic effect of tamoxifen in patients with ER-positive breast cancer.",
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