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Mol Carcinog. 2018 Jun;57(6):807-814. doi: 10.1002/mc.22795. Epub 2018 Mar 25.

Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition.

Author information

1
School of Medicine, Chengdu University, Chengdu, P.R China.
2
Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, P.R China.
3
Department of Urology, Chengdu University Hospital, Chengdu, P.R China.
4
Central Lab, Chengdu University Hospital, Chengdu, P.R China.
5
Department of Pathology, Shifang People's Hospital, Shifang, P.R China.
6
Department of Neurosurgery, Shifang People's Hospital, Shifang, P.R China.
7
School of Pharmacology and Bioengineering, Chengdu University, Chengdu, P.R China.

Abstract

Triptolide is an active component from a Chinese herb, Tripterygium wilfordii which has been applied for treating immune-related diseases over centuries. Recently, it was reported that a variety of cancer cell lines could be sensitized to DNA-damage based chemotherapy drugs in combination with Triptolide treatment. In the present study, we show that a short time exposure (3 h) to Triptolide, which did not trigger apoptosis, could specifically increase breast cancer cells sensitivity to Doxorubicin rather than other chemotherapy drugs including Paclitaxel, Fluorouracil, and Mitomycin C. Further studies revealed Triptolide downregulated ATM expression and inhibited DNA damage response to DNA double- strand breaks. Moreover, the chemosensitization effect to Doxorubicin from Triptolide was attenuated by overexpression of ATM in breast cancer cells. Our findings suggest that Triptolide specifically chemosensitizes breast cancer cells to Doxorubicin prior to apoptosis initiation through downregulating ATM expression and inhibiting DNA damage response.

KEYWORDS:

ATM; DNA damage response; Triptolide; chemosensitization

PMID:
29500880
DOI:
10.1002/mc.22795
[Indexed for MEDLINE]

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