Effects of flavonoids on reactive oxygen species and metastasis-associated ability in highly invasive A431-III sub-line
Date Issued
2015
Date
2015
Author(s)
Zhang, Wei-Jun
Abstract
Tumor metastasis has always been the main factor that causes the death of cancer patients, thus it is important to realize the mechanism of cancer metastasis. It has been appreciated for a number of years that reactive oxygen species (ROS) production is increased in malignant cancer cells. During tumor progression, reactive oxygen species can activate MMP activity, cell-ECM adhesion, and subsequently promotes the capability of cell migration and cell invasion. The signaling pathway involved in these processes are thought to be achieved through redox modification of signaling molecules such as protein kinases and transcription factors. In the previous study from our laboratory, we have selected highly invasive tumor cell sub-line A43-1III from A431-P by using Boyden Chamber Assay (unpublished data). In this study, we take the advantage of this highly invasive sub-line to further explore the role of reactive oxygen species in cancer cells. We find that reactive oxygen species production is increased in A431-III sub-line compared to A431-P. This result may attribute to differential expression of antioxidants, which were important in balancing cellular ROS levels. We find that MnSOD expression is increased whereas catalase is decreased in A431III sub-line compared to A431P. The flavonoids are polyphenolic compounds that are ubiquitous constituents of flowering plants, particularly food plants. Plant flavonoids have been recognized as possessing antitumor effects. Two dietary flavonoid constituents, luteolin (Lu) and quercetin (Qu), generally appear to be the most potent among plant flavonoids in terms of their in vitro biological activities. ROS level was decreased in A431-III sub-line after treatment of luteolin or quercetin. Furthermore, luteolin or quercetin treatment in A431-IIII sub-line promoted catalase expression on protein level. These results suggest that luteolin and quercetin can influence ROS elimination in cells by regulating the expression of antioxidant enzymes. Then, we tested the effect of ROS level in A431 cells. We promoted ROS level in A431-P by direct H2O2 treatment, and suppressed ROS level in A431-III by treating antioxidant, NAC and DPI. The capability of migration was promoted in A431-P and suppressed in A431-III. Experimental results are shown that the ability of flavonoids scavenging reactive oxygen species is associated with their anti-tumor activity.
Subjects
flavonoid
tumor
cancer
reactive oxygen species
SDGs
Type
thesis