We report isolation of a novel tumor-reversing gene, tentatively named SVS-1, encoding a protein of 820 amino acids with localization on the plasma membrane as a type I transmembrane protein.

The effect of the benzylic structure of lignan on antioxidant activity was evaluated. Secoisolariciresinol (1) and 3,4-bis(4-hydroxy-3-methoxybenzyl)tetrahydrofuran (2), which have two secondary benzylic positions without oxygen, showed the highest antioxidant activity. Optically active verrucosin (4) was synthesized for the first time in this experiment.

(1-4) Class I enzymes (topo I, EC 5.99.1.2) act by making a transient break in one DNA strand, allowing the DNA to swivel and release torsional strain, changing the linking number by steps of one.(2,4) Class II enzymes (topo II, EC 5.99.1.3) make transient breaks in both strands of one DNA molecule, allowing the passage of another DNA duplex through the gap, changing the linking number by steps of two.(1-3) These enzymes are crucial for cellular genetic processes such as DNA replication, transcription, recombination, and chromosome segregation at mitosis.It has long been accepted that topos are valuable targets of cancer chemotherapeutics.(2-5) Several classes of topo inhibitors have been introduced into cancer clinics as potent anticancer drugs, including camptothecin (CPT) derivatives (e.g. irinotecan and topotecan) inhibiting topo I (4) and anthracyclines (e.g. doxorubicin and mitoxantorone), epipodophyllotoxins (e.g. etoposide , aminoacridines (e.g. m-AMSA) and ellipticines targeting topo II.(4,5) These agents are active in both hematological and solid malignancies. The activity of these agents is thought to result from stabilization of the DNA /topo cleavable complex (CC), an intermediate in the catalytic cycle of the enzymes, (2,5,6) resulting ultimately in apoptosis. A number of new topo inhibitors have recently been reported that do not stabilize CC. Thus, two general mechanistic classes of topo inhibitors, especially for topo II, have recently been described: (7) (1) classical topo 'poisons' that stabilize CC and stimulate single-or double-strand cleavage of DNA, such as CPT and its derivatives, indolocarbazoles for topo I, and for topos I and II; and (2) catalytic inhibitors that prevent the catalytic cycle of the enzymes at steps other than cleavage intermediates, such as dioxopiperazines, (7,9,10) aclarubicin, (11) intoplicin, (12) and F11782.(13) Some of these compounds are dual inhibitors of topos I and II. The catalytic inhibitors of topo II, merbarone (14,15) and dioxopiperazines, (9,10) have been extensively studied and have been shown to inhibit the reopening of the closed clamp formed by the enzyme around DNA by inhibiting the ATPase activity of the enzyme, thus sequestering the enzyme within the cell. (7,16,17)

No abstract

No abstract