Antineoplastic activity, synergism, and antagonism of triarylalkylphosphonium salts and their combinations

Previously, some of us demonstrated that monocationic phosphonium salt [4-(formylphenyl)methyl]triphenylphosphonium chloride (A) and [4-(hydrazinocarboxy)-1-butyl]tris(4-dimethylaminophenyl)phosph oni um chloride (B) in combination, exhibit inhibitory synergism against ELA mammary carcinoma. Here we...

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Bibliographic Details
Published inAnticancer research Vol. 14; no. 1A; p. 21
Main Authors Patel, J, Rideout, D, McCarthy, M R, Calogeropoulou, T, Wadwa, K S, Oseroff, A R
Format Journal Article
LanguageEnglish
Published Greece 01.01.1994
Subjects
Animals
Antineoplastic Combined Chemotherapy Protocols - antagonists & inhibitors
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Cell Division - drug effects
Cercopithecus aethiops
Dose-Response Relationship, Drug
Drug Interactions
Drug Screening Assays, Antitumor
Drug Synergism
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Organophosphorus Compounds - antagonists & inhibitors
Organophosphorus Compounds - pharmacology
Rats
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Summary:Previously, some of us demonstrated that monocationic phosphonium salt [4-(formylphenyl)methyl]triphenylphosphonium chloride (A) and [4-(hydrazinocarboxy)-1-butyl]tris(4-dimethylaminophenyl)phosph oni um chloride (B) in combination, exhibit inhibitory synergism against ELA mammary carcinoma. Here we show that A + B also exhibits synergism against cultured MB49 murine bladder carcinoma, but antagonism against HT-29 human colon carcinoma. This is probably due to assembly of the hydrazone (C) in situ: synthetic C is a more potent growth inhibitor than either A or B for MB49 and ELA, yet inferior to B for HT-29 cells. A, B, C, [4-(hydrazinocarboxy)-1-butyl]tris(3-tolyl)phosphonium chloride (D) and [4-(methylcarboxy)butyl]triphenylphosphonium chloride (F) selectively inhibit carcinoma growth relative to untransformed cells, most likely due to high carcinoma transmembrane potentials. D and F are tolerated in mice at 100 mg/kg. Intraperitoneal administration of D slows subcutaneous HT-29 xenograft growth by 41 to 59% versus controls in nu/nu mice, and intraperitoneal administration of B slows MB49 xenograft growth by 46 to 57% versus controls and extends the median lifespan of mice bearing ELA breast carcinoma allografts by 86%. Triarylalkylphosphonium salts represent a promising class of antineoplastic cations exhibiting unusual selectivity and synergism.
ISSN:0250-7005