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WESTPORT, Jun 29 (Reuters Health) - Two agents have been identified that induce cytochrome C release and caspase 8-dependent apoptosis in human leukemia and melanoma cells. These findings may lead to the development of new chemotherapeutic agents, according to a paper published in the June 15th issue of Blood.
Dr. Shazib Pervaiz and colleagues, from the National University of Singapore, explain that results of their previous studies showed that "...photoactivation of lipophilic agent merocyanine 540 generates a mixture of photoproducts...that selectively induce cell death in human leukemia, lymphoma, and a variety of other tumor cell types."
The researchers' aim in the current study was to isolate the biologically active products in the photoactivated merocyanine 540 mixture. They purified two photoproducts, designated C1 and C2, that "...effectively induced apoptosis in HL60 [leukemic] and M14 [melanoma] cells."
According to the paper, "...C1 and C2 induced non-receptor-dependent activation of caspase 8, which was responsible for the downstream activation of caspase 3 and cell death."
The investigators also found that C1 and C2 induced the release of cytochrome C from mitochondria of HL60, M14 and purified rat liver cells,"...which suggests that both anticancer agents directly or indirectly induce mitochondrial events associated with apoptotic cell death."
Dr. Pervaiz's team observed that "C1-induced cytochrome C release was mediated by the mitochondrial permeability transition (MPT) pore and accompanied by a decrease in mitochondrial transmembrane potential." In contrast, the group found that C2-medited cytochrome C release "...was independent of MPT pore opening."
These findings, the authors say, "...do not exclude the possibility that changes in mitochondrial [transmembrane potentials] are critical for apoptosis in some instances, but support the notion that this may not be a universal step in the apoptotic process." New antitumor strategies based on direct activation of the apoptotic pathway may therefore be possible.
Blood 1999;93:4096-4108
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