Open AccessNovel sesquiterpene lactone analogues as potent anti‐breast cancer agents
Author(s) -
Nakagawa-Goto Kyoko,
Chen Jo-Yu,
Cheng Yu-Ting,
Lee Wai-Leng,
Takeya Munehisa,
Saito Yohei,
Lee Kuo-Hsiung,
Shyur Lie-Fen
Publication year - 2016
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2016.03.002
Subject(s) - cancer research , paclitaxel , in vivo , triple negative breast cancer , apoptosis , breast cancer , in vitro , chemotherapy , cancer , medicine , biology , biochemistry , microbiology and biotechnology
Triple‐negative breast cancer (TNBC) is associated with high grade, metastatic phenotype, younger patient age, and poor prognosis. The discovery of an effective anti‐TNBC agent has been a challenge in oncology. In this study, fifty‐eight ester derivatives (DETDs) with a novel sesquiterpene dilactone skeleton were organically synthesized from a bioactive natural product deoxyelephantopin (DET). Among them, DETD‐35 showed potent antiproliferative activities against a panel of breast cancer cell lines including TNBC cell line MDA‐MB‐231, without inhibiting normal mammary cells M10. DETD‐35 exhibited a better effect than parental DET on inhibiting migration, invasion, and motility of MDA‐MB‐231 cells in a concentration‐dependent manner. Comparative study of DETD‐35, DET and chemotherapeutic drug paclitaxel (PTX) showed that PTX mainly caused a typical time‐dependent G2/M cell‐cycle arrest, while DETD‐35 or DET treatment induced cell apoptosis. In vivo efficacy of DETD‐35 was evaluated using a lung metastatic MDA‐MB‐231 xenograft mouse model. DETD‐35 significantly suppressed metastatic pulmonary foci information along with the expression level of VEGF and COX‐2 in SCID mice. DETD‐35 also showed a synergistic antitumor effect with PTX in vitro and in vivo. This study suggests that the novel compound DETD‐35 may have a potential to be further developed into a therapeutic or adjuvant agent for chemotherapy against metastatic TNBC.