The development of cancer cell resistance to conventional treatments continues to be a major obstacle in the successful treatment of tumors of many types.The discovery of a highly efficient direct and indirect free ra...The development of cancer cell resistance to conventional treatments continues to be a major obstacle in the successful treatment of tumors of many types.The discovery of a highly efficient direct and indirect free radical scavenger,melatonin,in the mitochondrial matrix may be a factor in determining both the occurrence of cancer cell drug insensitivity as well as radioresistance.This relates to two of the known hallmarks of cancer,i.e.,exaggerated free radical generation in the mitochondria and the development ofWarburg type metabolism(glycolysis).The hypothesis elaborated in this report assumes that the high oxidative environment in the mitochondria contributes to a depression of local melatonin levels because of its overuse in neutralizing the massive amount of free radial produced.Moreover,Warburg typemetabolism and chemoresistance are functionally linked and supplementalmelatonin has been shown to reverse glycolysis and convert glucose processing to the type that occurs in normal cells.Since thismetabolic type is a key factor in determining chemoresistance,melatonin would predictably also negate cancer drug insensitivity.The possible mechanisms by which melatonin may interfere either directly or indirectly with drug resistance are summarized in the current review.展开更多
文摘The development of cancer cell resistance to conventional treatments continues to be a major obstacle in the successful treatment of tumors of many types.The discovery of a highly efficient direct and indirect free radical scavenger,melatonin,in the mitochondrial matrix may be a factor in determining both the occurrence of cancer cell drug insensitivity as well as radioresistance.This relates to two of the known hallmarks of cancer,i.e.,exaggerated free radical generation in the mitochondria and the development ofWarburg type metabolism(glycolysis).The hypothesis elaborated in this report assumes that the high oxidative environment in the mitochondria contributes to a depression of local melatonin levels because of its overuse in neutralizing the massive amount of free radial produced.Moreover,Warburg typemetabolism and chemoresistance are functionally linked and supplementalmelatonin has been shown to reverse glycolysis and convert glucose processing to the type that occurs in normal cells.Since thismetabolic type is a key factor in determining chemoresistance,melatonin would predictably also negate cancer drug insensitivity.The possible mechanisms by which melatonin may interfere either directly or indirectly with drug resistance are summarized in the current review.
