Ovatodiolide sensitizes aggressive breast cancer cells to doxorubicin, eliminates their cancer stem cell-like phenotype, and reduces doxorubicin-associated toxicity

Oluwaseun Adebayo Bamodu, Wen Chien Huang, David T W Tzeng, Alexander Wu, Liang Shun Wang, Chi-Tai Yeh, Tsu Yi Chao

研究成果: 雜誌貢獻文章

19 引文 (Scopus)

摘要

Triple-negative breast cancer (TNBC) is chemotherapy-refractory and associated with poor clinical prognosis. Doxorubicin (Doxo), a class I anthracycline and first-line anticancer agent, effective against a wide spectrum of neoplasms including breast carcinoma, is associated with several cumulative dose-dependent adverse effects, including cardiomyopathy, typhilitis, and acute myelotoxicity. This study evaluated the usability of Ovatodiolide (Ova) in sensitizing TNBC cells to Doxo cytotoxicity, so as to reduce Doxo effective dose and consequently its adverse effects. TNBC cell lines MDA-MB-231 and HS578T were used. Pre-treatment of the TNBC cells with 10 μM Ova 24 h before Doxo administration increased the Doxo anticancer effect (IC50 1.4 μM) compared to simultaneous treatment with Doxo ( IC50 1.8 μM), or Doxo alone (IC50 9.2 μM). Intracellular accumulation of Doxo was lowest in Ova pre-treated cells at all Doxo concentrations, when compared with Doxo or simultaneously treated cells. In comparison to the Doxo-only group, cell cycle analysis of MDA-MB-231 cells treated concurrently with 2.5 μM Ova and 1.25 μM Doxo showed increased percentage of cells arrested at G0/G1; however, pre-treatment with the same concentration of Ova 24 h before Doxo showed greater tumor growth inhibition, with a 2.4-fold increased percentage of cells in G0/G1 arrest, greater Doxo-induced apoptosis, and significantly reduced intracellular Doxo accumulation. Additionally, Ova-sensitized TNBC cells also lost their cancer stem cell-like phenotype evidenced by significant dissolution, necrosis of formed mammospheres. Taken together, these findings indicate that Ova sensitizes TNBC cells to Doxo and potentiates doxorubicin-induced elimination of the TNBC cancer stem cell-like phenotype.
原文英語
頁(從 - 到)125-134
頁數10
期刊Cancer Letters
364
發行號2
DOIs
出版狀態已發佈 - 八月 10 2015

指紋

Neoplastic Stem Cells
Doxorubicin
Breast Neoplasms
Phenotype
Triple Negative Breast Neoplasms
Inhibitory Concentration 50
ovatodiolide
Anthracyclines
Cardiomyopathies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

引用此文

@article{ed19a9f9054e4807aefd83da6cf1fb5d,
title = "Ovatodiolide sensitizes aggressive breast cancer cells to doxorubicin, eliminates their cancer stem cell-like phenotype, and reduces doxorubicin-associated toxicity",
abstract = "Triple-negative breast cancer (TNBC) is chemotherapy-refractory and associated with poor clinical prognosis. Doxorubicin (Doxo), a class I anthracycline and first-line anticancer agent, effective against a wide spectrum of neoplasms including breast carcinoma, is associated with several cumulative dose-dependent adverse effects, including cardiomyopathy, typhilitis, and acute myelotoxicity. This study evaluated the usability of Ovatodiolide (Ova) in sensitizing TNBC cells to Doxo cytotoxicity, so as to reduce Doxo effective dose and consequently its adverse effects. TNBC cell lines MDA-MB-231 and HS578T were used. Pre-treatment of the TNBC cells with 10 μM Ova 24 h before Doxo administration increased the Doxo anticancer effect (IC50 1.4 μM) compared to simultaneous treatment with Doxo ( IC50 1.8 μM), or Doxo alone (IC50 9.2 μM). Intracellular accumulation of Doxo was lowest in Ova pre-treated cells at all Doxo concentrations, when compared with Doxo or simultaneously treated cells. In comparison to the Doxo-only group, cell cycle analysis of MDA-MB-231 cells treated concurrently with 2.5 μM Ova and 1.25 μM Doxo showed increased percentage of cells arrested at G0/G1; however, pre-treatment with the same concentration of Ova 24 h before Doxo showed greater tumor growth inhibition, with a 2.4-fold increased percentage of cells in G0/G1 arrest, greater Doxo-induced apoptosis, and significantly reduced intracellular Doxo accumulation. Additionally, Ova-sensitized TNBC cells also lost their cancer stem cell-like phenotype evidenced by significant dissolution, necrosis of formed mammospheres. Taken together, these findings indicate that Ova sensitizes TNBC cells to Doxo and potentiates doxorubicin-induced elimination of the TNBC cancer stem cell-like phenotype.",
keywords = "Breast cancer, Cancer stem cell, Doxorubicin, Drug toxicity, Ovatodiolide, TNBC",
author = "Bamodu, {Oluwaseun Adebayo} and Huang, {Wen Chien} and Tzeng, {David T W} and Alexander Wu and Wang, {Liang Shun} and Chi-Tai Yeh and Chao, {Tsu Yi}",
year = "2015",
month = "8",
day = "10",
doi = "10.1016/j.canlet.2015.05.006",
language = "English",
volume = "364",
pages = "125--134",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
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TY - JOUR

T1 - Ovatodiolide sensitizes aggressive breast cancer cells to doxorubicin, eliminates their cancer stem cell-like phenotype, and reduces doxorubicin-associated toxicity

AU - Bamodu, Oluwaseun Adebayo

AU - Huang, Wen Chien

AU - Tzeng, David T W

AU - Wu, Alexander

AU - Wang, Liang Shun

AU - Yeh, Chi-Tai

AU - Chao, Tsu Yi

PY - 2015/8/10

Y1 - 2015/8/10

N2 - Triple-negative breast cancer (TNBC) is chemotherapy-refractory and associated with poor clinical prognosis. Doxorubicin (Doxo), a class I anthracycline and first-line anticancer agent, effective against a wide spectrum of neoplasms including breast carcinoma, is associated with several cumulative dose-dependent adverse effects, including cardiomyopathy, typhilitis, and acute myelotoxicity. This study evaluated the usability of Ovatodiolide (Ova) in sensitizing TNBC cells to Doxo cytotoxicity, so as to reduce Doxo effective dose and consequently its adverse effects. TNBC cell lines MDA-MB-231 and HS578T were used. Pre-treatment of the TNBC cells with 10 μM Ova 24 h before Doxo administration increased the Doxo anticancer effect (IC50 1.4 μM) compared to simultaneous treatment with Doxo ( IC50 1.8 μM), or Doxo alone (IC50 9.2 μM). Intracellular accumulation of Doxo was lowest in Ova pre-treated cells at all Doxo concentrations, when compared with Doxo or simultaneously treated cells. In comparison to the Doxo-only group, cell cycle analysis of MDA-MB-231 cells treated concurrently with 2.5 μM Ova and 1.25 μM Doxo showed increased percentage of cells arrested at G0/G1; however, pre-treatment with the same concentration of Ova 24 h before Doxo showed greater tumor growth inhibition, with a 2.4-fold increased percentage of cells in G0/G1 arrest, greater Doxo-induced apoptosis, and significantly reduced intracellular Doxo accumulation. Additionally, Ova-sensitized TNBC cells also lost their cancer stem cell-like phenotype evidenced by significant dissolution, necrosis of formed mammospheres. Taken together, these findings indicate that Ova sensitizes TNBC cells to Doxo and potentiates doxorubicin-induced elimination of the TNBC cancer stem cell-like phenotype.

AB - Triple-negative breast cancer (TNBC) is chemotherapy-refractory and associated with poor clinical prognosis. Doxorubicin (Doxo), a class I anthracycline and first-line anticancer agent, effective against a wide spectrum of neoplasms including breast carcinoma, is associated with several cumulative dose-dependent adverse effects, including cardiomyopathy, typhilitis, and acute myelotoxicity. This study evaluated the usability of Ovatodiolide (Ova) in sensitizing TNBC cells to Doxo cytotoxicity, so as to reduce Doxo effective dose and consequently its adverse effects. TNBC cell lines MDA-MB-231 and HS578T were used. Pre-treatment of the TNBC cells with 10 μM Ova 24 h before Doxo administration increased the Doxo anticancer effect (IC50 1.4 μM) compared to simultaneous treatment with Doxo ( IC50 1.8 μM), or Doxo alone (IC50 9.2 μM). Intracellular accumulation of Doxo was lowest in Ova pre-treated cells at all Doxo concentrations, when compared with Doxo or simultaneously treated cells. In comparison to the Doxo-only group, cell cycle analysis of MDA-MB-231 cells treated concurrently with 2.5 μM Ova and 1.25 μM Doxo showed increased percentage of cells arrested at G0/G1; however, pre-treatment with the same concentration of Ova 24 h before Doxo showed greater tumor growth inhibition, with a 2.4-fold increased percentage of cells in G0/G1 arrest, greater Doxo-induced apoptosis, and significantly reduced intracellular Doxo accumulation. Additionally, Ova-sensitized TNBC cells also lost their cancer stem cell-like phenotype evidenced by significant dissolution, necrosis of formed mammospheres. Taken together, these findings indicate that Ova sensitizes TNBC cells to Doxo and potentiates doxorubicin-induced elimination of the TNBC cancer stem cell-like phenotype.

KW - Breast cancer

KW - Cancer stem cell

KW - Doxorubicin

KW - Drug toxicity

KW - Ovatodiolide

KW - TNBC

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JO - Cancer Letters

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