Cytotoxicity of a Quinone-containing Cockroach Sex Pheromone in Human Lung Adenocarcinoma Cells.
The cytotoxic effects of blattellaquinone (BTQ), a sex pheromone produced by adult female German cockroaches, have been studied using human lung adenocarcinoma A549 cells. 1,4-Benzoquinone (BQ), a toxic chemical implicated in benzene toxicity, was used as a reference compound. Both BQ and BTQ showed comparable toxicity toward A549 cells, with LD50 values estimated to be 14 and 19 microM, respectively. These two compounds increased the formation of an oxidized fluorescent probe, 2',7'-dichlorofluorescein, but had no effect on the cellular GSSG level. Interestingly, BTQ increased the level of 8-epi-prostaglandin F2alpha and was 4-fold more efficient in depleting cellular GSH content than BQ. Of the five GSH adducts of BTQ isolated, three were identified as mono-GSH conjugates, and the other two were di-conjugates. Mass spectrometric and NMR analyses of the di-conjugates showed that the second GSH molecule displaced the isovaleric acid moiety, potentially via a nucleophilic substitution reaction. The ability of BTQ to conjugate a second GSH molecule without quinone regeneration indicated that it may be a more effective cross-linking agent than BQ. Future experiments may be needed to evaluate the overall safety of BTQ before the commercialization of the compound as a cockroach attractant.
Ma
Bennett
B
Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. bennett_ma@merck.com
Carr
Brian A
BA
Krolikowski
Paul
P
Chang
Frank N
FN
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D003058:Cockroaches / Q000737:chemistry*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D011809:Quinones / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012724:Sex Attractants / Q000737:chemistry / Q000633:toxicity*
D011809:Quinones; D017382:Reactive Oxygen Species; D012724:Sex Attractants; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D019803:Glutathione Disulfide