Wu, X., Yue, G. L., Qiu, M. H., Lau, B. S., & Wong, C. K. Investigation on the anti-metastatic activities of a triterpenoid actein in breast cancer. International Conference of the Modernization of Chinese Medicine & Health Products, Hong Kong, 12 August 2016.

Abstract

Breast cancer is currently the second leading cause of cancer-related death among women in USA, and a continuous increase in incidence has also been observed in Hong Kong in recent decades. To date, the standard therapies could not diminish the rate of metastasis which leads to an especially low life span. Hence, anti-metastatic agents are still urgently needed. In this study, we investigated the potential anti-metastatic activities of actein, a cycloartane triterpene isolated from black cohosh and other Cimicifuga species, which has previously been reported to inhibit the growth of human breast cancer cells in vitro.

In this study, human breast cancer cells MDA-MB-231 were used. MTT assay was conducted to evaluate the cell viability, while effects of actein on cell motility and migration were assessed by scratch wound healing assay and transwell migration assay, respectively. For in vivo study, MDA-MB-231 cells were stained with a fluorescent dye prior to microinjection into the zebrafish embryos. Cancer cell dissemination was observed under fluorescent microscopy after 5 days treatment with different concentrations of actein. The extent of metastasis was reflected as different percentages of cancer cells dissemination from the xenograft site and thus the anti-metastatic effect of actein could be evaluated.

Our results showed that actein inhibited the growth of breast cancer cells in vitro, with IC50 value of 62 µM in MDA-MB-231 cells. Actein (10-40 µM) significantly inhibited the motility of MDA-MB-231 cells. Besides, the inhibitory activities of actein on migration of MDA-MB-231 cells were also significant at the dose of 20-40 µM. In vivo study also showed that actein at 40 and 60 µM decreased the injected cancer cells migration by 7.8% and 83.0%, respectively, at 5 days post injection.

In conclusion, actein could induce anti-metastasis effects in breast cancer cells in vitro and decreased cancer cell migration in zebrafish embryos. Further studies in xenograft-bearing mouse model will be used to confirm the anti-metastatic activity of actein.

Jiao, D., Wong, C. K., Qiu, H., & Lam, C. W. K. TLR2 and NOD2 mediated activation of basophils and eosinophils interacting with dermal fibroblasts: a link between concurrent Staphylococcus aureus infection and atopic dermatitis. The Hong Kong Allergy Convention 2014, Hong Kong, 4-5 October 2014.

 

Abstract

Patients with atopic dermatitis (AD) have a unique predisposition to colonization or infection by Staphylococcus aureus (S. aureus), which is believed to exacerbate or contribute to persistent skin inflammation by the activation of nucleotide-binding oligomerization domain 2 (NOD2) and Toll like receptor 2 (TLR2) in AD. To better understand the role of S. aureus involved in AD, the effects of heat-killed S. aureus (HKSA) and S. aureus-associated NOD2 and TLR2 ligands on the interaction of basophils/eosinophils and human dermal fibroblasts (HDF) were investigated. We found that HKSA could significantly up-regulate cell surface expression of intercellular adhesion molecule (ICAM-1) on eosinophils and HDF, as well as induce AD-related cytokines/chemokines in co-culture of basophils/eosinophils and HDF. By using flow cytometric analysis, both NOD2 and TLR2 protein were constitutively expressed of basophils/eosinophils and HDF. The increased cell surface expression of ICAM-1 and cytokines/chemokines secretion in co-culture were observed under the stimulation of NOD2 ligand MDP, TLR2 ligand peptidylglycan (PGN), lipoteichoic acid (LTA) and Pam3Cys (Pam3CKs) as well as HKSA. Intracellular nuclear factor (NF)-кB, p38-mitogen activated protein kinase (MAPK) and extracellular regulated protein kinases (ERK)-MAPK play regulatory roles for the expression of adhesion molecules and cytokines/chemokines in co-culture. Moreover, in vivo studies also showed that topical application of NOD2/TLR2 ligands exacerbate AD-like symptoms in an AD mice model induced by MC903. These results indicate the important role of NOD2 and TLR2 involved in the innate immune responses for S. aureus infection in AD and the immunopathological mechanisms by which S. aureus infection can exaggerate the inflammation in AD.