2′-Benzoyloxycinnamaldehyde Induces Apoptosis in Human Carcinoma via Reactive Oxygen Species

Abstract

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 M 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.

Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells

“…The DNA damage signaling for apoptosis can also be attributed to a higher expression of p52, a TFIIH transcription factor having a death domain that is involved in transcription of proapoptotic proteins and in activation of cell death. 46,47 The higher level of NF-kB2 transcripts and proteins in Cbl cos cells than in Cbl-treated cells may have a significant role in activating apoptosis.…”

2-Hydroxycinnamaldehyde Inhibits SW620 Colon Cancer Cell Growth Through AP-1 Inactivation

“…Direct activation of caspase-3 by MAP kinase activation could be possible. In this point, it is noteworthy that 2'-bezoyloxyxinnamaldehyde induces apoptosis of human breast and colon cancer cells via activation of caspase-3 in a p53-independent manner (29). Possible mechanisms are proposed in Fig.…”

Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death

“…Cinnamaldehyde contains active Michael acceptor pharmacophore and is given the Generally Recognized as Safe status with approval for use in food in the United States 22 . Cinnamaldehyde has been reported to induce ROS generation mainly in the mitochondria and inhibit growth of human cancer cells, but minimal cytotoxicity to normal cells 21,23,24 . However, the clinical applications of cinnamaldehyde have been limited by its poor bioavailability (a short half-life in blood) due to rapid oxidation of aldehyde group and lower drug efficacy than common anticancer drugs 21,25,26 .…”