UM E-Theses Collection (澳門大學電子學位論文庫)
Title
Anti-cancer effects of Ganoderma lucidum triterpenoids
English Abstract
Ganoderma lucidum triterpenoids (GLTs), structurally a class of highly oxidized lanostanes, have been demonstrated to exhibit a board spectrum of anti-cancer properties, which include anti-proliferative, anti-metastatic, anti-oxidative, and antiinflammatory effects, etc. Recently, some purified compounds from these triterpenoids were tested for anti-cancer effect in vitro and in vivo, and several possible targets involved in this process were identified. However, the specific signal pathways and precise molecular mechanisms responsible for their anti-cancer properties remain unclear. In this study, three forms of G. luciudm triterpenoids, an ethanol-soluble acidic component (ESAC) from G. lucidum, several pure ganoderic acids (GA-DM, GA-A, GA-F) and a mixture mainly contain ganoderiol A and its analogues (GAEE), were used to systemically analyze their anti-cancer effects in vitro and in zebrafish model. So far the acquired achievements are summarized and listed as follows: (1) The anti-proliferative effects of ESAC and GA-DM against human breast cancer cells are confirmed. DNA damage, G1 cell cycle arrest and apoptosis are closely related to the growth inhibition. (2) To clarify the anti-angiogenic effects of G. lucidum triterpenoids, transgenic Tg (fli1: EGFP) zebrafish model is used to screen potential compounds. G. lucidum triterpenoids treatment does not inhibit angiogenesis in zebrafish, and ESAC exposure shows a slight promoter on angiogenesis. Moreover, ESAC truly protect blood vessel from zebrafish vascular damage, which suggests a vascular protective role of G. lucidum triterpenoids. (3) GAEE is shown to inhibit adhesion and migration abilities of highly metastatic breast cancer MDA-MB-231 cells. However, GAEE treatment does not alter the expression and enzyme activities of matrix metalloproteinase (MMP) and 4 urokinase plaminogen activator (uPA), and has no effect on transactivation of nuclear factor-kappa B (NF-κB), which is mainly responsible for cell invasion. The underlying mechanism revealed that GAEE decreases the expression of focal adhesion kinase (FAK) and attenuates the interaction of FAK and SRC, hence blocks paxillin activation, and results in inactivation of RhoA, CDC42, which are responsible for cell adhesion and migration. These results suggest that GAEE may be a potential anti-cancer agent targeting FAK-SRC-paxillin signaling. Based on the scientific work we carried out and the achievements mentioned above, we conclude that the anti-cancer profile of GLTs is promising and further studies are needed to potentiate these triterpenoids as anti-cancer agents.
Issue Date
2013
Author
Wu, Guo Sheng,
Faculty
Institute of Chinese Medical Sciences
Degree
Ph.D.
Subject
Ganodermataceae -- Therapeutic use
Cancer -- Alternative treatment
Medicinal plants -- China
Biomedical Sciences -- Institute of Chinese Medical Sciences

Supervisor
王一濤
Library URL
b3131974
Files In This Item:
TOC & Abstract
Full-text
Location
1/F Zone C
Supervisor
--