Kyoko Nakagawa-Goto*, Jo-Yu Chen, Yu-Ting Cheng, Wai-Leng Lee, Munehisa Takeya, Yohei Saito, Kuo-Hsiung Lee*, and Lie-Fen Shyur* (2016) Novel sesquiterpene lactone analogues as potent anti-breast cancer agents. Molecular Oncology, 2016, 10(6):921-937
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.
2017/08/21 10:30 AM
Dr. Chia-Lin Chung (Associate Professor, Department of Plant Pathology and Microbiology, National Taiwan University)
Bakanae of rice: new insights into an emerging old disease
Dr. Chung uses quantitative genetics approaches such as linkage mapping and genome-wide association mapping, in combined with molecular markers or whole-genome sequencing analysis, to dissect defense mechanisms against blast and bakanae disease in rice.
Auditorium A134, Agricultural Technology Building, Agricultural Biotechnology Research Center 2017/08/28 10:30 AM
Dr. Ho-Ming Chen (Assistant Research Fellow, Agricultural Biotechnology Research Center, Academia Sinica)
Toward RNA interference 2.0: new insights into the biogenesis, action, and movement of plant small RNA
Auditorium A134, Agricultural Technology Building, Agricultural Biotechnology Research Center