UCP2-related mitochondrial pathway participates in oroxylin A-induced apoptosis in human colon cancer cells.

Abstract

Oroxylin A is a flavonoid extracted from the root of Scutellaria baicalensis Georgi. Our previous research demonstrated that oroxylin A have various anti-tumor effects including apoptosis, cell cycle arrest, drug-resistant reversion, and others. This paper explores the mechanism how oroxylin A induce apoptosis by regulating uncoupling protein 2 (UCP2) in human colon cancer cells. We found that the inhibition of UCP2 by UCP2 siRNA significantly increased the sensitivity of cells to drugs, reactive oxygen species (ROS) generation and the opening of mitochondrial permeability transition pore (MPTP) of CaCo-2 cells. We also found that UCP2 inhibition could lead to ROS-mediated MPTP activation. Furthermore, we demonstrated that oroxylin A triggered MPTP-dependent pro-apoptotic protein release from mitochondria to matrix and then induced apoptotic cascade by inhibiting UCP2. Intriguingly, the inhibition of UCP2 by oroxylin A was able to block Bcl-2 translocation to the mitochondria, keeping MPTP at open-state. In conclusion, we have demonstrated that UCP2 plays a key role in mitochondrial apoptotic pathway; UCP2s inhibition by oroxylin A triggers the MPTP opening, and promotes the apoptosis in CaCo-2 cells.

• Authors: Chen Qiao, Libin Wei, Qinsheng Dai, Yuxin Zhou, Qian Yin, Zhiyu Li, Yuanming Xiao, Qinglong Guo, Na Lu
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 230 Issue 5 Pg. 1054-63 (May 2015) ISSN: 1097-4652 [Electronic] United States
• PMID: 25251374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Flavonoids
• Ion Channels
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Mitochondrial Proteins
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• UCP2 protein, human
• Uncoupling Protein 2
• 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
• Doxorubicin

Topics

• Apoptosis (drug effects)
• Caco-2 Cells
• Colonic Neoplasms (metabolism, pathology)
• Doxorubicin (pharmacology)
• Drug Screening Assays, Antitumor
• Flavonoids (chemistry, pharmacology)
• HCT116 Cells
• Humans
• Ion Channels (antagonists & inhibitors, drug effects, metabolism)
• Mitochondria (drug effects, metabolism)
• Mitochondrial Membrane Transport Proteins (metabolism)
• Mitochondrial Permeability Transition Pore
• Mitochondrial Proteins (antagonists & inhibitors, drug effects, metabolism)
• Protein Transport (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Uncoupling Protein 2