Hinokiflavone induces apoptosis via activating mitochondrial ROS/JNK/caspase pathway and inhibiting NF-κB activity in hepatocellular carcinoma.

Journal of Cellular and Molecular Medicine
Wan MuXiaoyu Li

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common malignancy with limited treatment options. Hinokiflavone (HF), a natural biflavonoid, has shown to inhibit the proliferation of melanoma, whereas its antitumour effect against HCC and the underlying mechanisms remain elusive. Here, we aimed at evaluating its antitumour effect against HCC in both in vitro and in vivo. Cell counting kit 8, colony formation assay, PI/RNase staining and Western blotting revealed that HF inhibited the proliferation of HCC cells via G0/G1 cell cycle arrest with p21/p53 up-regulation. DAPI staining, Annexin V-FITC/PI staining and Western blotting confirmed that HF triggered caspase-dependent apoptosis. Moreover, HF increased the levels of mitochondrial reactive oxygen species (mtROS) and activated c-Jun N-terminal kinase (JNK) pathway, as measured by MitoSOX Red staining and Western blotting. After respectively inhibiting mtROS (Mito-TEMPO) and JNK (SP600125), HF-induced apoptosis was reversed. Additionally, Western blotting documented that HF suppressed nuclear factor kappa B (NF-κB) activity and the anti-apoptotic genes downstream, contributing to cell apoptosis. Finally, in vivo studies demonstrated that HF significantly impaired tumour growth...Continue Reading

References

May 12, 1994·Nature·J M KyriakisJ R Woodgett
Mar 21, 2001·Apoptosis : an International Journal on Programmed Cell Death·H U SimonF Levi-Schaffer
Sep 15, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·S KrickJ X Yuan
Nov 8, 2001·Current Opinion in Cell Biology·J Bartek, J Lukas
Dec 26, 2001·Pharmacology & Therapeutics·K C ZimmermannD R Green
Jan 1, 2003·Seminars in Cancer Biology·Sharon Amit, Yinon Ben-Neriah
Jun 20, 2003·Cell Proliferation·Katrien VermeulenZwi N Berneman
Nov 25, 2003·Oncogene·Alexei DegterevJunying Yuan
Oct 22, 2005·Nature Reviews. Cancer·Stephen W Fesik
Mar 17, 2006·Free Radical Biology & Medicine·Han-Ming Shen, Zheng-gang Liu
Oct 11, 2008·Cell Death and Differentiation·G KroemerUNKNOWN Nomenclature Committee on Cell Death 2009
Feb 5, 2011·Nature Reviews. Gastroenterology & Hepatology·Tom Luedde, Robert F Schwabe
May 21, 2013·Cancer Letters·Thippeswamy GulappaChendil Damodaran
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
Apr 15, 2015·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Ayman M SalehMohammad Azhar Aziz
Aug 19, 2015·Biotechnology Advances·Atanas G AtanasovHermann Stuppner
Nov 4, 2015·Antioxidants & Redox Signaling·Yeon Ju YangTong-Shin Chang
Mar 22, 2016·Oxidative Medicine and Cellular Longevity·Jixiang ZhangWeiguo Dong
Nov 9, 2016·Mini Reviews in Medicinal Chemistry·Vanessa Silva GontijoClaudio Viegas
Mar 17, 2018·Clinics and Research in Hepatology and Gastroenterology·Jose J G MarinRocio I R Macias
Apr 1, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jianguo WuLi Wang
Apr 11, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shuping YangYongmei Xie
Apr 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sun-Yup ShimMina Lee
Sep 22, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chien-Ying LeeYu-Hsiang Kuan
Mar 5, 2019·Journal of Pharmaceutical and Biomedical Analysis·Yuting ChenLantong Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
xenograft
fluorescence microscopy
flow
nuclear translocation
xenografts

Software Mentioned

FACS Calibur
GraphPad
ModFit LT
GraphPad Prism
Image
Pro Plus

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.