Antitumor effects of two novel naturally occurring terpene quinones isolated from the Mediterranean ascidian Aplidium conicum.
ABSTRACT The ascidian Aplidium conicum collected along Sardinia coasts (Italy) contained two novel prenylated benzoquinones, designated thiaplidiaquinone A (1) and thiaplidiaquinone B (2). These compounds showed an unprecedented tetracyclic structure. We have studied the pro-apototic mechanisms of both prenylated benzoquinones in the Jurkat cell line that is derived from a human T lymphoma, and we show that both compounds induce a strong production of intracellular reactive oxygen species (ROS) in this cell line. Moreover, kinetic experiments, comparing the timing of ROS induction with the collapse of the mitochondria potential (DeltaPsi(m)), clearly showed that ROS preceded the disruption of the mitochondrial potential, and the later one paralleled the appearance of apoptotic cells. Thus, thiaplidiaquinones A and B can enter into the cells and induce cell death by apoptosis.
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ABSTRACT: We have studied aspects of the regulatory interrelationship between the plasma membrane oxidoreductase (PMOR) system and the mitochondrial respiratory capacity of human Namalwa cells. Although the role of mitochondria in the maintenance of cellular redox and energetic states is well established, the PMOR system in comparison is a poorly characterized enzyme system whose functions, particularly in relation to cellular metabolism, have not been clearly elucidated. Therefore we compared the PMOR and mitochondrial respiratory activities of human Namalwa cells during the induction by ethidium bromide treatment of rho 0 cells, which lack a functional mitochondrial respiratory system. The plasma membrane NADH-ferricyanide reductase activity of the PMOR system was found to increase in a stepwise manner concomitant with a decline in cellular mitochondrial respiratory activity. Addition of p-chloromercuriphenylsulfonic acid to the culture medium, at a concentration totally inhibiting the plasma membrane NADH-ferricyanide reductase in vitro, leads to cell death of rho 0 but not of rho + cells. Thus, the up-regulation of a functional PMOR system is a necessary phenomenon in maintaining the viability of mammalian rho 0 cells.Journal of Biological Chemistry 01/1995; 269(48):30097-100. · 4.65 Impact Factor
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ABSTRACT: Some varieties of sweet pepper accumulate non-pungent isosters of capsaicin, a type of compounds exemplified by capsiate. The only structural difference between capsaicin and capsiate is the link between the vanillyl and the acyl moieties, via an amide bond in the former and via an ester bond in the latter. By flow cytometry analyses we have determined that nor-dihydrocapsiate, a simplified analogue of capsiate, is a pro-oxidant compound that induces apoptosis in the Jurkat tumor cell line. The nuclear DNA fragmentation induced by nor-dihydrocapsiate is preceded by an increase in the production of reactive oxygen species and by a subsequent disruption of mitochondria transmembrane potential. Capsiate-induced apoptosis is initiated at the S phase of the cell cycle and is mediated by a caspase-3-dependent pathway. The accumulation of intracellular reactive oxygen species in capsiate-treated cells is greatly prevented by the presence of ferricyanide, suggesting that capsiates target a cellular redox system distinct from the one involved in the mitochondrial electron-chain transport. Methylation of the phenolic hydroxyl of nor-dihydrocapsiate completely abrogated the ability to induce reactive oxygen species and apoptosis, highlighting the relevance of the presence of a free phenolic hydroxyl for the pro-oxidant properties of capsaicinoids.Free Radical Research 07/2003; 37(6):611-9. · 3.28 Impact Factor
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ABSTRACT: The notion of transmembrane electron transport is usually associated with mitochondria and chloroplasts. However, since the early 1970s, it has been known that this phenomenon also occurs at the level of the plasma membrane. Ever since, evidence has accumulated for the existence of a plethora of transplasma membrane electron transport enzymes. In this review, we discuss the various enzymes known, their molecular characteristics and their biological functions.Redox Report 02/2003; 8(1):3-21. · 1.66 Impact Factor