UM E-Theses Collection (澳門大學電子學位論文庫)
Title
Anti-oxidative and pro-oxidative effects of curcuminoids on cellular senescence in aging and cancer
English Abstract
Curcuminoids, the major active components of Curcuma longa (薑黃), attract increasing interest due to their favourable therapeutic effects with low toxicity. Notably, curcuminoids exert a wide spectrum of benefits in disease conditions that are closely related to functional declines with age, such as cardiovascular diseases, neurodegenerative diseases and cancer. In addition, recent studies demonstrated that curcuminoids extend lifespan in model organisms. Hence, curcuminoids represent promising candidates for the promotion of healthy aging. In this study, the systematic beneficial effects of curcuminoids in regard to aging and aging-related disorders were explored. This study focused on the effects of curcuminoids on the regulation of redox homeostasis in different cell types including normal and cancer cells that might help to reflect comparable underlying mechanisms in aging, cardiovascular diseases and cancers. Major achievements of this study are summarized as follows: (1) The protective and anti-aging effects of curcuminoids against t-BHP-induced oxidative damage in human WI38 fibroblasts have been demonstrated for the first time. Curcuminoid prevented t-BHP-caused senescence-like phenomenon in fibroblasts and is thought to interfere with senescence-related pathways. (2) The action mechanism of curcuminoids might be related to the concept of hormesis, which proposes that mild stress could result in hormetic response with beneficial effects such as anti-aging. It is interesting to point out that while the t-BHP-stimulated ROS generation in WI38 fibroblasts could almost be prevented completely by longer pretreatment (48 h) of curcuminoids, a shorter pretreatment (90 min) had an opposite effect and increased the cellular ROS level rapidly. Thus, it is postulated that short duration of curcuminoid pretreatment might act as a hormetic stress which could enhance the rescue of oxidative damage later on. (3) The activation of SIRT1 by curcuminoids in WI38 fibroblasts has been reported for the first time in this study. SIRT1 has been proved to be the principal mediator of caloric restriction (CR) to extend lifespan. Curcuminoids could increase both the translational and transcriptional levels of SIRT1. Whereas, inhibition on SIRT1 by pharmacological or genetic approaches attenuated the benefit of curcuminoids. These observations might imply that curcuminoids could mediate improvements in disorders through regulatory systems related to CR such as maintaining glucose homeostasis and insulin sensitivity via the stimulation of SIRT1. (4) Pretreatments (48 h) of various concentrations of curcuminoids increased the cell viability of t-BHP-stimulated endothelial cells (HUVECs), and significantly prevented the morphological damages induced by t-BHP including the loss of cell attachment, cell shrinkage, nucleus pycnosis and apoptotic body formation. ERK1/2 and PI3K/Akt signaling pathways were shown to be involved in the protective mechanisms of curcuminoids against t-BHP-induced damage in HUVECs. (5) It is suggested that the pro-oxidant action played an important role in the mechanism of the anti-cancer properties of curcuminoids in MCF-7 cells. The results showed that oxidative stress stimulated by curcuminoids may induce cellular senescence in cancer cells, which may add a novel facet in the anti-cancer actions of curcuminoids. (6) The present study highlighted that curcuminoids could exert differential effects on the regulation of redox system in different cell types. In normal fibroblasts and endothelial cells, the pretreatments of curcuminoids protected them from oxidative insults, either by enhancing oxidative defense systems or by regulating relevant signaling pathways. On the other hand, in malignant MCF-7 breast cancer cells, curcuminoids suppressed cancer cell growth probably by increasing oxidative stress and subsequently enhancing cellular senescence. In summary, the present study has provided evidence for the systematic beneficial effects of curcuminoids in aging, disease states and cancer. The results added further evidence of the importance of free radicals in the process of aging and related-disorders. Therefore, the regulation of redox homeostasis might provide an efficienct approach to maintain healthy aging.
Issue Date
2011
Author
Li, Ying Bo
Faculty
Institute of Chinese Medical Sciences
Degree
Ph.D.
Subject
Herbs -- Therapeutic use -- China
Materia medica -- China -- Analysis
Medicinal plants -- China -- Analysis
Cells -- Aging
Cancer -- Treatment -- China
Biomedical Sciences -- Institute of Chinese Medical Sciences
Supervisor
王一濤
Library URL
b2492795
Files In This Item:
TOC & Abstract
Full-text
Location
1/F Zone C
Supervisor
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