2'-benzoyloxycinnamaldehyde induces apoptosis in human carcinoma via reactive oxygen species.
2'-hydroxycinnamaldehyde (HCA) has been shown to have inhibitory effects on farnesyl protein transferase in vitro, angiogenesis, and tumor cell growth. However, mechanism for these inhibitions remains unknown. As a derivative of HCA, BCA (2'-benzoyl-oxycinnamaldehyde) was synthesized by replacing hydroxyl group with benzoyl-oxyl group. When p53-mutated cancer cell lines (MDA-MB-231 breast cancer cell and SW620 colon cancer cell) were treated with 10 microM HCA or BCA, it induced growth arrest and apoptosis of tumor cells. Markers of apoptosis such as degradations of chromosomal DNA and poly(ADP-ribose) polymerase and activation of caspase-3 were detected after HCA or BCA treatment. BCA-induced apoptosis was blocked by pretreatment of cells with anti-oxidants, glutathione, or N-acetyl-cysteine. In addition, BCA-induced activation of caspase-3 and degradation of poly(ADP-ribose) polymerase were abolished by pretreatment of cells with the anti-oxidants. These results suggest that reactive oxygen species are major regulator of BCA-induced apoptosis. HCA or BCA-induced accumulation of reactive oxygen species was detected by using DCF-DA, an intracellular probe of oxidative stress. Furthermore, when BCA (100 mg/kg) was administrated intraperitoneally or orally into a nude mouse, it inhibited >88 or 41% of tumor growth, respectively, without any detectable weight change. These results suggest that BCA is a good drug candidate for cancer therapy.
Han
Dong Cho
DC
Korea Research Institute of Bioscience and Biotechnology, 52 Uendong Yoosunggu, Taejeon 305-600, Korea.
Lee
Mi-Young
MY
Shin
Ki Deok
KD
Jeon
Sun Bok
SB
Kim
Jung Min
JM
Son
Kwang-Hee
KH
Kim
Hyoung-Chin
HC
Kim
Hwan-Mook
HM
Kwon
Byoung-Mog
BM
D000111:Acetylcysteine / Q000737:chemistry; D000171:Acrolein / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D000447:Aldehydes / Q000494:pharmacology*; D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism; D051231:Farnesyltranstransferase; D005434:Flow Cytometry; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018384:Oxidative Stress; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011233:Precipitin Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species; D013997:Time Factors
C484327:2'-benzoyloxycinnamaldehyde; D000447:Aldehydes; D000970:Antineoplastic Agents; D000975:Antioxidants; D001565:Benzoates; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D000171:Acrolein; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D066246:ErbB Receptors; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D000111:Acetylcysteine