title: Antitumor agents. 21. A proposed mechanism for inhibition of cancer growth by tenulin and helenalin and related cyclopentenones.
abstract: Evidence is presented that sesquiterpene lactones or ketones containing the O=CC=CH2 moiety, e.g., tenulin and helenalin, alkylate the thiol group of reduced glutathione and L-cysteine in vitro. A proposal is offered that this mechanism of action is responsible for the observed potent in vivo antitumor activity of these agents in the Ehrlich ascites and Walker 256 carcinosarcoma and to a lesser extent in the P388 leukemic screen. Inhibition of tumor growth is thought to occur due to the O=CC=CH2 system alkylating by rapid Michael addition the SH biological nucleophiles of key regulatory enzymes of nucleic acid and chromatin metabolism. This proposition is in accord with the ability of these agents to inhibit DNA synthesis and gene activity of Ehrlich ascites cells.
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001202:Ascitic Fluid / Q000378:metabolism; D002279:Carcinoma 256, Walker / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology; D003545:Cysteine; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005978:Glutathione; D006639:Histidine; D007783:Lactones / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000378:metabolism; D007945:Leukemia, Lymphoid / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009363:Neoplasm Proteins / Q000096:biosynthesis; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002843:Chromatin; D003517:Cyclopentanes; D004273:DNA, Neoplasm; D007783:Lactones; D009363:Neoplasm Proteins; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C011124:tenulin; C001329:helenalin; D006639:Histidine; D005978:Glutathione; D003545:Cysteine