| 摘要 |
A method to improve the effectiveness of cancer treatments by increasing the production of specific ACYL-chain dihydroceramide(s). Increase of native chain-length dihydroceramides is directly cytotoxic to human acute lymphoblastic leukemia cell line MOLT-4 ALL cells with a cytotoxic potency that is dependent upon the specific fatty acid acyl-chain length and saturation of the dihydroceramides. The combination of sphinganine and GT-11 lead to cell death in the absence of an increase of reactive oxygen species, suggesting that the ability of fenretinide to increase cytotoxic ROS is mechanistically independent of dihydroceramides increase and related cytotoxicity. Most unexpectedly, supplementing the exposure of cancer cells to a dihydroceramide-increasing anti-hyperproliferative agent(s), such as fenretinide, with specifically-chosen fatty acids can increase the cytotoxicity of the anti-hyperproliferative agent to the cancer cells to a beneficial effect.
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