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Inhibition of cyclooxygenase-2 and induction of apoptosis in estrogen-nonresponsive breast cancer cells by Antrodia camphorata
You-Cheng Hseua, Ssu-Ching Chenb, Pei-Chuan Tsaie, Chee-Shan Chenc, Fung-Jou Lud, Nai-Wen Change and Hsin-Ling Yangf, ,
aDepartment of Cosmeceutics, China Medical University, Taichung, Taiwan
bDepartment of Biotechnology, National Kaohsiung Normal University, Kaohsiung, Taiwan
cDepartment of Applied Chemistry, Chao Yang University of Technology, Taichung, Taiwan
dDepartment of Applied Chemistry, Chun Shan Medical University, Taichung, Taiwan
eDepartment of Biochemistry, China Medical University, Taichung, Taiwan
fInstitute of Nutrition, China Medical University, 91 Hsueh Shih Road, 40421 Taichung, Taiwan
Abstract
The objective of this study was to investigate the fermented culture broth of Antrodia camphorata (A. camphorata) to induce apoptosis and inhibit cyclooxygenase-2 (COX-2) in estrogen-nonresponsive (MDA-MB-231) human breast cancer cells.
Treatment of the highly invasive MDA-MB-231 cells with A. camphorata (40–240 ìg/ml) resulted in dose and time-dependent sequences of events marked by apoptosis, as evidenced by loss of cell viability, chromatin condensation, and internucleosomal DNA fragmentation.
Apoptosis in the MDA-MB-231 cells was accompanied by release of cytochrome c, activation of caspase-3, -8, and -9, and specific proteolytic cleavage of poly (ADP-ribose) polymerase (PARP). Although the A. camphorata-induced apoptosis was associated with a reduction in Bcl-2 protein levels, negligible Bax increase was observed.
Furthermore, A. camphorata treatment inhibited COX-2 protein expression and prostaglandin E2 (PGE2) production in MDA-MB-231 cells. Analysis of the study data suggests that A. camphorata exerts growth inhibition on (highly invasive) estrogen-nonresponsive human breast cancer cells through apoptosis induction associated with COX-2 inhibition, and that it may possess anticancer properties potentially valuable for application in drug products.
Food and Chemical Toxicology
Volume 45, Issue 7, July 2007, Pages 1107-1115
doi:10.1016/j.fct.2006.12.012
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