Induction of apoptosis and caspase-3 activation by chemopreventive [6]-paradol and structurally related compounds in KB cells.
[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.
Keum
Young Sam
YS
Oral Cancer Research Institute, Department of Oral Pathology and Oral Biology, College of Dentistry, Yonsei University, Seoul 120-752, South Korea.
Kim
Jin
J
Lee
Keun Hyung
KH
Park
Kwang Kyun
KK
Surh
Young Joon
YJ
Lee
Jong Min
JM
Lee
Sang Sup
SS
Yoon
Jung Hoon
JH
Joo
So Yeon
SY
Cha
In Ho
IH
Yook
Jong In
JI
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000517:prevention & control; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004790:Enzyme Induction; D005434:Flow Cytometry; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology*; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000517:prevention & control; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D000970:Antineoplastic Agents; D007659:Ketones; D006139:Guaiacol; C421614:6-paradol; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases