Medicinal & Aromatic Plants
Open Access
ISSN: 2167-0412
+44 1300 500008
ISSN: 2167-0412
+44 1300 500008
Yi-Shiou Chiou
National Taiwan University of Food Science,Taiwan
Posters & Accepted Abstracts: Med Aromat Plants
Breast cancer is a significant threat to women's health and has high incidence and mortality. Metastasis in breast cancer patients is a major cause of cancer deaths among women worldwide. Clinical experience suggests that patients with metastatic Triple-Negative Breast Cancer (TNBC) relapse quickly and often have chemotherapy resistance. Taxol (paclitaxel) is an effective chemotherapeutic agent for treating metastatic breast cancer, but Taxol at high doses can cause adverse effects and recurrent resistance. Thus, select synergistic combination therapy is recommended, which is safer and has a more significant response rate than monotherapy. In this study, our strategy is to combine a low dose of Taxol (5 mg/kg, i.p.) and garcinol (1 mg/kg,i.g.) to investigate the synergistic antitumor and anti-metastasis effects and to determine the underlying mechanisms of these effects in vivo. For the in vivo study, metastasis-specific mouse mammary carcinoma 4T1 cells were inoculated in Balb/c mice to establish an orthotopic primary tumor and spontaneous metastasis model. Tumor growth and metastases were monitored. The mechanisms of synergistic efficacies were evaluated at different signaling, including proliferation, survival, and Epithelial-Mesenchymal Transition (EMT)-regulated metastatic propensity. We demonstrated that garcinol combined with Taxol significantly increased therapeutic efficacy when compared with either treatment alone. The synergistic antitumor and anti-metastasis effects were enhanced primarily through induction of Taxol-stimulated G2/M phase arrest and inhibition of caspase-3/cytosolic Ca2+-independent phospholipae A2 (iPLA2) and nuclear factor-kB (NF- B)/Twist-related protein 1 (Twist1) drive downstream events including tumor cell repopulation, survival, inflammation, angiogenesis, invasion, and EMT. Our current findings provide the first experimental evidence that a combination of a low dose of Taxol and garcinol is a promising therapeutic strategy for controlling advanced or metastatic breast cancer. Finally, our results also point to the role of NF- B/Twist1 and caspase-3/iPLA2 signaling pathways might be as a biomarker to predict tumor response to treatment.
Yi-Shiou Chiou has completed her PhD at the age of 34 years from National Cheng Kung University and postdoctoral studies from National Taiwan University of Food Science and Technology. She has been working with various in vitro and in vivo models realizing basic theories and mechanisms underlining relationship between bioactive nutraceuticals and chemoprevention. She is very active to participate in various national and international academic conferences. She has also published more than 20 papers in reputed journals and receive many positive comments from experts in related field.