Benzoyloxycinnamaldehyde Research Articles

Physicochemical properties of 2′-benzoyloxycinnamaldehyde

2′-Benzoyloxycinnamaldehyde (BCA), a derivative of 2-hydroxycinnamaldehyde demonstrated a potent antitumor effect against several human solid tumor cell lines. The physicochemical properties and degradation kinetics of BCA were investigated to support the drug-development effort. The aqueous solubility of BCA was low, and it was not considered to be hygroscopic. The degradation of BCA followed the first-order kinetics, and the pH-rate profile revealed that the degradation of BCA was governed by general acid- and specific base-catalysis as well as spontaneous hydrolysis. BCA was very unstable in basic conditions, in particular pH above 9, and found to be more stable in acidic conditions such as pH between 2 and 4. The degradation of BCA was accelerated in elevated temperature and high-ionic strength. Therefore, it was suggested that BCA should be stored in slightly acidic conditions with lowered temperature and ionic strength.

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.