Sanguinarine Induces Apoptosis of Human Oral Squamous Cell Carcinoma KB Cells via Inactivation of the PI3K/Akt Signaling Pathway.

Abstract

Preclinical Research Sanguinarine, an alkaloid isolated from the root of Sanguinaria canadensis and other plants of the Papaveraceae family, selectively induces apoptotic cell death in a variety of human cancer cells, but its mechanism of action requires further elaboration. The present study investigated the pro-apoptotic effects of sanguinarine in human oral squamous cell carcinoma KB cells. Sanguinarine treatment increased DR5/TRAILR2 (death receptor 5/TRAIL receptor 2) expression and enhanced the activation of caspase-8 and cleavage of its substrate, Bid. Sanguinarine also induced the mitochondrial translocation of pro-apoptotic Bax, mitochondrial dysfunction, cytochrome c release to the cytosol, and activation of caspase-9 and -3. However, a pan-caspase inhibitor, z-VAD-fmk, reversed the growth inhibition and apoptosis induced by sanguinarine. Sanguinarine also suppressed the phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt in KB cells, while co-treatment of cells with sanguinarine and a PI3K inhibitor revealed synergistic apoptotic effects. However, pharmacological inhibition of AMP-activated protein kinase and mitogen-activated protein kinases did not reduce or enhance sanguinarine-induced growth inhibition and apoptosis. Collectively, these findings indicate that the pro-apoptotic effects of sanguinarine in KB cells may be regulated by a caspase-dependent cascade via activation of both intrinsic and extrinsic signaling pathways and inactivation of PI3K/Akt signaling. Drug Dev Res 77 : 227-240, 2016.   © 2016 Wiley Periodicals, Inc.

• Authors: Tae Kyung Lee, Cheol Park, Soon-Jeong Jeong, Moon-Jin Jeong, Gi-Young Kim, Wun-Jae Kim, Yung Hyun Choi
• Journal: Drug development research (Drug Dev Res) Vol. 77 Issue 5 Pg. 227-40 (08 2016) ISSN: 1098-2299 [Electronic] United States
• PMID: 27363951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents, Phytogenic
• Benzophenanthridines
• Isoquinolines
• sanguinarine
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• Caspases

Topics

• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Benzophenanthridines (isolation & purification, pharmacology)
• Carcinoma, Squamous Cell (drug therapy, pathology)
• Caspases (metabolism)
• Humans
• Isoquinolines (isolation & purification, pharmacology)
• KB Cells
• Mouth Neoplasms (drug therapy, pathology)
• Phosphatidylinositol 3-Kinase (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Sanguinaria (chemistry)
• Signal Transduction (drug effects)