Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation
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AbstractColorectal cancer is the second most common cause of cancer death in the world and about half of the patients with colorectal cancer require adjuvant therapy after surgical resection. Therefore, the eradication of cancer cells via chemotherapy constitutes a viable approach to treating patients with colorectal cancer. In this study, the effects of bufalin isolated from a traditional Chinese medicine were evaluated and characterized in HT-29 and Caco-2 human colon cancer cells. Contrary to its well-documented apoptosis-promoting activity in other cancer cells, bufalin did not cause caspase-dependent cell death in colon cancer cells, as indicated by the absence of significant early apoptosis as well as poly(ADP-ribose) polymerase and caspase-3 cleavage. Instead, bufalin activated an autophagy pathway, as characterized by the accumulation of LC3-II and the stimulation of autophagic flux. The induction of autophagy by bufalin was linked to the generation of reactive oxygen species (ROS). ROS activated autophagy via the c-Jun NH(2)-terminal kinase (JNK). JNK activation increased expression of ATG5 and Beclin-1. ROS antioxidants (N-acetylcysteine and vitamin C), the JNK-specific inhibitor SP600125, and JNK2 siRNA attenuated bufalin-induced autophagy. Our findings unveil a novel mechanism of drug action by bufalin in colon cancer cells and open up the possibility of treating colorectal cancer through a ROS-dependent autophagy pathway. (C) 2011 Elsevier Inc. All rights reserved.
All Author(s) ListXie CM, Chan WY, Yu S, Zhao J, Cheng CHK
Journal nameFree Radical Biology and Medicine
Year2011
Month10
Day1
Volume Number51
Issue Number7
PublisherElsevier
Pages1365 - 1375
ISSN0891-5849
eISSN1873-4596
LanguagesEnglish-United Kingdom
KeywordsApoptosis; Autophagy; Bufalin; Cancer therapy; Cell death; Colon cancer; JNK; LC3; ROS
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Endocrinology & Metabolism; ENDOCRINOLOGY & METABOLISM

Last updated on 2020-04-07 at 01:57