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Flavonoids of Korean Citrus aurantium L. Induce Apoptosis via Intrinsic Pathway in Human Hepatoblastoma HepG2 Cells.

Authors
  • Lee, Seung Hwan1
  • Yumnam, Silvia1
  • Hong, Gyeong Eun1
  • Raha, Suchismita1
  • Saralamma, Venu Venkatarame Gowda1
  • Lee, Ho Jeong1
  • Heo, Jeong Doo2
  • Lee, Sang Joon2
  • Lee, Won-Sup3
  • Kim, Eun-Hee4
  • Park, Hyeon Soo1
  • Kim, Gon Sup1
  • 1 Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, 660-701, Korea. , (North Korea)
  • 2 Gyeongnam Department of Environment Toxicology and Chemistry, Toxicity Screening Research Center, Korea Institute of Toxicology, Jinju, Korea. , (North Korea)
  • 3 Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongnam Regional Cancer Center, Gyeongsang National University Hospital, Jinju, 660-702, Korea. , (North Korea)
  • 4 Department of Nursing Science, International University of Korea, Jinju, 660-759, Korea. , (North Korea)
Type
Published Article
Journal
Phytotherapy Research
Publisher
Wiley (John Wiley & Sons)
Publication Date
Dec 01, 2015
Volume
29
Issue
12
Pages
1940–1949
Identifiers
DOI: 10.1002/ptr.5488
PMID: 26439681
Source
Medline
Keywords
License
Unknown

Abstract

Korean Citrus aurantium L. has long been used as a medicinal herb for its anti-inflammatory, antioxidant, and anticancer properties. The present study investigates the anticancer role of flavonoids extracted from C. aurantium on human hepatoblastoma cell, HepG2. The Citrus flavonoids inhibit the proliferation of HepG2 cells in a dose-dependent manner. This result was consistent with the in vivo xenograft results. Apoptosis was detected by cell morphology, cell cycle analysis, and immunoblot. Flavonoids decreased the level of pAkt and other downstream targets of phosphoinositide-3-kinase/Akt pathway - P-4EBP1 and P-p70S6K. The expressions of cleaved caspase 3, Bax, and Bak were increased, while those of Bcl-2 and Bcl-xL were decreased with an increase in the expression of Bax/Bcl-xL ratio in treated cells. Loss of mitochondrial membrane potential was also observed in flavonoid-treated HepG2 cells. It was also observed that the P-p38 protein level was increased both dose and time dependently in flavonoid-treated cells. Collectively, these results suggest that flavonoid extracted from Citrus inhibits HepG2 cell proliferation by inducing apoptosis via an intrinsic pathway. These findings suggest that flavonoids extracted from C. aurantium L. are potential chemotherapeutic agents against liver cancer.

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