A team from the USA and Switzerland investigated the levels of ceramide, a candidate lipid mediator of apoptosis, in human metastatic colorectal cancer.
In addition, the in vitro and in vivo effects of various ceramide analogues in inducing apoptosis in colon cancer were tested.
Ceramide levels were measured in fresh human specimens of primary and metastatic colon cancer obtained from patients undergoing surgery. In each subject, ceramide levels in primary colon cancer were compared with normal colon mucosa.
The researchers found that human colon cancer showed more than a 50% decrease in the cellular content of ceramide when compared with normal colon mucosa.
Application of ceramide analogues and ceramidase inhibitors induced rapid cell death through activation of various proapoptotic molecules, such as caspases and release of cytochrome c.
Ceramidase inhibition increased the ceramide content of tumor cells, resulting in maximum activation of the apoptotic cascade.
|Ceramide analogues may be effective in treatment of colonic carcinoma.|
Normal liver cells were completely resistant to inhibitors of ceramidases.
The researchers found that treatment of nude mice with B13, the most potent ceramidase inhibitor, completely prevented tumor growth, using two different aggressive human colon cancer cell lines metastatic to the liver.
Dr Markus Selzner said on behalf of the group, "B13 and related analogues of ceramide and inhibitors of ceramidases offer a promising therapeutic strategy, with selective toxicity toward malignant - but not normal - cells."
"These studies also suggest that the ceramide content in cancer cells might be involved in the pathogenesis of tumor growth in vitro and in vivo," he concluded.