Induction of apoptosis and caspase-3 activation by chemopreventive [6]-paradol and structurally related compounds in KB cells.

Abstract

[6]-paradol, a pungent phenolic substance found in ginger and other Zingiberaceae plants, has been demonstrated to be an effective inhibitor of tumor promotion in mouse skin carcinogenesis. In the present study, we found that [6]-paradol and other structurally related derivatives, [10]-paradol, [3]-dehydroparadol, [6]-dehydroparadol, and [10]-dehydroparadol, with the exception of [3]-paradol induce apoptosis in an oral squamous carcinoma cell line, KB, in a dose-dependent manner. [10]-paradol and [10]-dehydroparadol exhibited a similar extent of cytotoxicity to that of [6]-paradol. [6]-Dehydroparadol and [3]-dehydroparadol appeared to be more potent, with an IC50 less than 40 microM. Treatment of KB cells with an apoptosis-inducing concentration of [6]-dehydroparadol caused induction of proteolytic cleavage of pro-caspase-3. These results suggest that [6]-paradol and structurally related derivatives induce apoptosis through a caspase-3-dependent mechanism.

• Authors: Young Sam Keum, Jin Kim, Keun Hyung Lee, Kwang Kyun Park, Young Joon Surh, Jong Min Lee, Sang Sup Lee, Jung Hoon Yoon, So Yeon Joo, In Ho Cha, Jong In Yook
• Journal: Cancer letters (Cancer Lett) Vol. 177 Issue 1 Pg. 41-7 (Mar 08 2002) ISSN: 0304-3835 [Print] Ireland
• PMID: 11809529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Ketones
• Guaiacol
• 6-paradol
• CASP3 protein, human
• Casp3 protein, mouse
• Caspase 3
• Caspases

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Carcinoma, Squamous Cell (enzymology, prevention & control)
• Caspase 3
• Caspases (metabolism)
• Cell Survival (drug effects)
• DNA Fragmentation
• Enzyme Induction
• Flow Cytometry
• Guaiacol (analogs & derivatives, chemistry, pharmacology)
• Humans
• Ketones (chemistry, pharmacology)
• Mouth Neoplasms (enzymology, prevention & control)
• Tumor Cells, Cultured (cytology, drug effects)