Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem cells and primary breast cancer cells

Li,Junjie; Liu,Ruilei; Yang,Ye; Huang,Yong; Li,Xi; Liu,Ruiming; Shen,Xiaoyan

doi:10.3892/or.2014.3115

May-2014 Volume 31 Issue 5

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May-2014 Volume 31 Issue 5

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Article

Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem cells and primary breast cancer cells

Authors:
- Junjie Li
- Ruilei Liu
- Ye Yang
- Yong Huang
- Xi Li
- Ruiming Liu
- Xiaoyan Shen
View Affiliations / Copyright

Affiliations: Department of Breast Surgery, Sichuan Cancer Hospital, Chengdu 610041, P.R. China, Department of Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China, Department of Pulmonary Tumor, Sichuan Cancer Hospital, Chengdu 610041, P.R. China, Laboratory of Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, P.R. China, Laboratory of Pharmacology and Toxicology, College of Pharmacy, Sun Yat-sen University, Guangzhou 510006, P.R. China
Pages: 2181-2186
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Published online on: March 27, 2014

https://doi.org/10.3892/or.2014.3115
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Abstract

We investigated the potential efficacy of the Chinese herbal extract triptolide for the treatment of human breast cancer by measuring the triptolide-induced cytotoxicity in cultures of human primary breast cancer cells (BCCs) and breast cancer stem cells (BCSCs) in vitro and in vivo. Human BCCs and BCSCs from invasive ductal carcinoma samples were cultured and treated with 0.1, 0.5 or 1.0 µM triptolide. Cell death and apoptosis were measured after 24, 48 and 72 h of treatment. Mammospheres were found to be highly tumorigenic when implanted subcutaneously in nude BALB/c mice. Triptolide was cytotoxic against both human primary BCCs and BCSCs in vitro (P<0.05), but the cytotoxicity was stronger against the BCCs. In response to 1 µM triptolide for 72 h, the apoptotic rates were approximately 60% for BCCs and 30% for BCSCs. The BCSCs exhibited a high formation rate of tumors when implanted subcutaneously in nude BALB/c mice. Triptolide treatment in vivo significantly inhibited tumor growth compared with mock treatment. In conclusion, the cytotoxicity of triptolide against BCCs and BCSCs in vitro and in vivo suggests that this natural diterpenoid triepoxide compound may have clinical applications for the suppression of breast tumor growth.

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1	Bonnet D and Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 3:730–737. 1997. View Article : Google Scholar : PubMed/NCBI
2	Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI
3	Liu J, Jiang Z, Xiao J, et al: Effects of triptolide from Tripterygium wilfordii on ERalpha and p53 expression in two human breast cancer cell lines. Phytomedicine. 16:1006–1013. 2009.
4	Lu L, Kanwar J, Schmitt S, et al: Inhibition of tumor cellular proteasome activity by triptolide extracted from the Chinese medicinal plant ‘thunder god vine’. Anticancer Res. 31:1–10. 2011.PubMed/NCBI
5	Yang S, Chen J, Guo Z, et al: Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther. 2:65–72. 2003.PubMed/NCBI
6	Pigneux A, Mahon FX, Uhalde M, et al: Triptolide cooperates with chemotherapy to induce apoptosis in acute myeloid leukemia cells. Exp Hematol. 36:1648–1659. 2008. View Article : Google Scholar : PubMed/NCBI
7	Zhou Y, Xu Q and Huang Y: An in vitro study of Triptolide inhibiting proliferation of vascular endothelial cells. Practical J China. 6:564–566. 2004.
8	Lou YJ, Jin J and Wang YG: Triptolide inhibits transcription factor NF-kappaB and induces apoptosis of multiple myeloma cells. Leuk Res. 29:99–105. 2005. View Article : Google Scholar : PubMed/NCBI
9	Alvi AJ, Clayton H, Joshi C, et al: Functional and molecular characterisation of mammary side population cells. Breast Cancer Res. 5:R1–R8. 2003. View Article : Google Scholar : PubMed/NCBI
10	Chen Y and Rittling SR: Novel murine mammary epithelial cell lines that form osteolytic bone metastases: effect of strain background on tumor homing. Clin Exp Metastasis. 20:111–120. 2003. View Article : Google Scholar : PubMed/NCBI
11	Moltzahn FR, Volkmer JP, Rottke D and Ackermann R: ‘Cancer stem cells’ - lessons from Hercules to fight the Hydra. Urol Oncol. 26:581–589. 2008.
12	Liu S, Dontu G and Wicha MS: Mammary stem cells, self-renewal pathways and carcinogenesis. Breast Cancer Res. 7:86–95. 2005. View Article : Google Scholar : PubMed/NCBI
13	Abraham BK, Fritz P, McClellan M, Hauptvogel P, Athelogou M and Brauch H: Prevalence of CD44⁺/CD24^−/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res. 11:1154–1159. 2005.PubMed/NCBI
14	Ling LJ, Wang S, Liu XA, et al: A novel mouse model of human breast cancer stem-like cells with high CD44⁺CD24^−/lower phenotype metastasis to human bone. Chin Med J. 121:1980–1986. 2008.PubMed/NCBI
15	Ponti D, Costa A, Zaffaroni N, et al: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65:5506–5511. 2005. View Article : Google Scholar : PubMed/NCBI
16	Ginestier C, Hur MH, Charafe-Jauffret E, et al: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 1:555–567. 2007. View Article : Google Scholar : PubMed/NCBI
17	Fan M, Yan PS, Hartman-Frey C, et al: Diverse gene expression and DNA methylation profiles correlate with differential adaptation of breast cancer cells to the antiestrogens tamoxifen and fulvestrant. Cancer Res. 66:11954–11966. 2006. View Article : Google Scholar : PubMed/NCBI
18	Eriksson M, Guse K, Bauerschmitz G, et al: Oncolytic adenoviruses kill breast cancer initiating CD44⁺CD24^−/low cells. Mol Ther. 15:2088–2093. 2007. View Article : Google Scholar : PubMed/NCBI
19	Qiu D and Kao PN: Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f. Drugs R D. 4:1–18. 2003. View Article : Google Scholar : PubMed/NCBI
20	Yang S, Chen J, Guo Z, et al: Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther. 2:65–72. 2003.PubMed/NCBI
21	Frese S, Pirnia F, Miescher D, et al: PG490-mediated sensitization of lung cancer cells to Apo2L/TRAIL-induced apoptosis requires activation of ERK2. Oncogene. 22:5427–5435. 2003. View Article : Google Scholar : PubMed/NCBI
22	Zhang P, Zhang R and Wang Y: Research progress on the antitumor molecular mechanism of triptolide. Acta Chin Med Pharmacol. 3:79–82. 2009.(In Chinese).

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem cells and primary breast cancer cells

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