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Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition
Author(s) -
Deng Yu,
Li Fulun,
He Pinglin,
Yang Yafei,
Yang Jin,
Zhang Yamei,
Liu Junying,
Tong Yongping,
Li Qingfeng,
Mei Xian,
Shu Zengyi,
Zhao Qi
Publication year - 2018
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22795
Subject(s) - triptolide , tripterygium wilfordii , doxorubicin , apoptosis , dna damage , biology , cancer research , paclitaxel , mcf 7 , chemotherapy , pharmacology , breast cancer , cancer cell , cancer , dna , medicine , pathology , biochemistry , human breast , genetics , alternative medicine
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.