Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0267964 (PAA)
 2,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro cytotoxic activity profile of nine novel phenylarsonic acid (CAS 98-05-5, PAA) compounds against 17 human cancer cell lines including (a) ovarian cancer cell lines ES-2, PA-1, CAOV-3, OVCAR-3, (b) testicular cancer cell lines Ntera-2, Tera-2, N2NICP, 833K, and 64CP, (c) multiple myeloma cell lines ARH77, HS-Sultan, RPMI-8226, and U266, and (d) acute lymphoblastic leukemia (ALL) cell lines NALM-6, MOLT-3, ALL-1, and RS4; 11, was determined by the MTT assay. The lead compounds, 2-methylthio-4-[(4'-aminophenylazo)-phenylarsonic acid] pyrimidine (PHI-370) and 2-methylthio-4-(4'-phenylarsonic acid)-aminopyrimidine (PHI-380) caused apoptotic death in all 17 cancer cell lines at low micromolar concentrations, as documented by TUNEL assays and confocal laser scanning microscopy. PHI-380 was also tested and found to be very active against primary tumor cells isolated from surgical biopsy specimens of 14 patients with therapy-refractory non-small cell lung cancer, breast cancer, colon cancer, lymphoma, hepatoblastoma, or Wilm's tumor as well. Because of their broad-spectrum and potent anticancer activity and ability to induce apoptosis in primary tumor cells from therapy-refractory cancer patients, PAA compounds such as PHI-370 and PHI-380 may provide the basis for effective salvage regimens for patients with recurrent cancer.
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PMID:Phenylarsonic acid compounds with broad-spectrum and potent cytotoxic activity against human cancer cells. 1287 14

Diphenylarsinic acid [DPAA(V)] was detected in ground water used as drinking water after a poisonous incident in Kamisu, Japan. An approach to define the target molecules of DPAA(V) with a high throughput analysis of proteins from cultured human cells demonstrated down-regulation of glutaminase C (GAC). GAC is a splicing variant of the kidney-type glutaminase (KGA) gene and has the enzyme activity of phosphate-activated glutaminase (PAG). To gain some insights into the mechanism of arsenic intoxication in Kamisu, the effects of various arsenic compounds, including arsenicals that were detected in ground water ([DPAA(V)], phenylarsonic acid [PAA(V)] and bis(diphenylarsine)oxide [BDPAO(III)]) and rice (phenylmethylarsinic acid [PMAA(V)]), were investigated for the expression of GAC and PAG activity. When cultured human HepG2 cells were incubated with arsenicals for 24h, the pentavalent phenylarsenic form of PAA(V) and PMAA(V) as well as DPAA(V) suppressed the expression of GAC protein and PAG activity in a concentration-dependent manner. On the other hand, the trivalent phenylarsenic form of BDPAO(III) had no suppressive effect on GAC and PAG. In addition, trivalent phenylarsenic compounds, such as the glutathione (GSH) conjugate of DPAA(V) [DPA-GS (III)] and triphenylarsine [TPA(III)], and the inorganic arsenics, iAs(V) and iAs(III), and methylated metabolites of inorganic arsenics, dimethylarsinic acid [DMA(V)] and dimethylarsinous acid [DMA(III)], had no suppressive effect on glutaminase. Likewise, methyl substituents of the hydroxyl groups of DPAA(V), PAA(V) and PMAA(V), diphenylmethylarsine oxide [DPMAO(V)] and phenyldimethylarsine oxide [PDMAO(V)], did not have any suppressive effects. These results suggest that pentavalent arsenic compounds with both phenyl groups and hydroxyl groups are effective in the suppression of glutaminase. In addition, the fact that it was only the arsenicals detected in Kamisu that were effective in suppressing glutaminase provides insights into the cause of the arsenic intoxication at Kamisu.
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PMID:Structure-effect relationship in the down-regulation of glutaminase in cultured human cells by phenylarsenic compounds. 1942 35