Bitter Orange Peel Extract Induces Autophagy In Human Hepatoma Cells
Date Issued
2015
Date
2015
Author(s)
Lee, Huey-Yin
Abstract
Liver cancer is the second major cancer related death in the world. There are only 16% of 5-year relative survival rate among liver cancer patients because of the poor prognosis and cancer therapy side effects. To relieve the uncomfortable symptoms, natural adjuvant has become an alternative trend instead of conventional treatment. Polymethoxyflavones (PMFs) are a group of flavones found in citrus fruits peel. Tangeretin and nobiletin are major compounds in PMFs which their potential biological activities have been reported, such as anti-inflammation, anti-diabetes and anti-cancer. The objectives of this study are to investigate the anti-liver cancer activity of bitter orange peel extract (BOPE) and its molecular mechanisms in human hepatoma Hep 3B cells. The results showed that BOPE effectively reduced Hep 3B cell viability with the IC50 of 48.95 μg/mL at 24 hours. In addition, BOPE induced LC3 aggregation and conversion of LC3-I to LC3-II, which required for autophagosome formation, without increasing hypodiploid proportion and plasma membrane leakage. These results demonstrated that BOPE induced cell death of Hep 3B cells by autophagy rather than apoptosis and necrosis. In this study, we also investigated the molecular mechanisms of BOPE-induced cell autophagy. Results showed that BOPE promoted ROS generation and ATP depletion in Hep 3B cells, leading to ER stress, following by elevatation of cytosolic calcium ion concentration and activation of AMPK/TSC2/mTOR and DAPK/Beclin-1 pathways. Furthermore, major components of BOPE, tangeretin and nobiletin, exhibited synergistic effect to inhibit cell viability in Hep 3B cells. In conclusion, tangeretin and nobiletin from BOPE can synergistically induce ER-stress mediated cell death by autophagy in human hepatoma Hep 3B cells and it could be used as a potential complementary agent for liver cancer therapy.
Subjects
liver cancer
bitter orange peel extract
polymethoxyflavones
autophagy
combination effect
SDGs
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-104-R02641043-1.pdf
Size
23.54 KB
Format
Adobe PDF
Checksum
(MD5):748db9faf1f04e71fd5c5035e55909fe