title: Combination of three metals for the treatment of cancer: gallium, rhenium and platinum. 1. Determination of the optimal schedule of treatment.
abstract: Platinum is well known for its anticancer activity, firstly used as cis-diaminedichloroplatinum (II) (CDDP), with a wide range of activity. Its main mechanism of action involves its binding to DNA. Gallium, another metal, has also demonstrated apoptotic effects on malignant cells, but through interaction with targets other than DNA, such as the membrane, cytoskeleton and proteasome, and on enzyme activities. An antitumor synergism between CDDP and both gallium and rhenium compounds has been demonstrated. For these reasons, we proposed to combine these three metals and to determine at which doses each compound could be administered without major toxicity. CDDP, tetrakis(1-octanol) tris(5-aminosalicylate)gallium(III), and a diseleno-ether rhenium(I) complex were used in this experimental study in breast cancer MCF-7 tumor-bearing mice. CDDP was administered intraperitoneally (i.p.) twice a week at the dose of 3 mg/kg. Tetrakis(1-octanol) tris(5-aminosalicylate) gallium (III) and rhenium(I) diseleno-ether complexes were administered orally, daily, five days a week for three weeks, at doses ranging from 20 to 100 mg/kg for the gallium compound and from 10 to 50 mg/kg for the rhenium compound. Doses of 10 mg/kg of rhenium(I) diseleno-ether, and 100 mg/kg of the salicylate gallium compound, in combination with CDDP induced a significant decrease of 50% of the tumor volume, by comparison with the control group. In contrast, the decrease of the tumor volume in mice treated by CDDP alone was less than 25%. Changes in the sequence of administration of the three metals will be discussed to improve the therapeutic index.
authors: Oncology Department, Polyclinic Maymard, Bastia, France. philippe.collery@gmail.com
authors: Philippe
authors: P
authors: Collery
authors: Ahmed
authors: A
authors: Mohsen
authors: Anthony
authors: A
authors: Kermagoret
authors: Jean
authors: J
authors: D'Angelo
authors: Georges
authors: G
authors: Morgant
authors: Didier
authors: D
authors: Desmaele
authors: Alain
authors: A
authors: Tomas
authors: Thomas
authors: T
authors: Collery
authors: Ming
authors: M
authors: Wei
authors: Abdelfattah
authors: A
authors: Badawi
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D056831:Coordination Complexes / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D005708:Gallium / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012211:Rhenium / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays
chemical_list: D056831:Coordination Complexes; D012211:Rhenium; D005708:Gallium; D002945:Cisplatin