title: A mixture of amino acids and other small molecules present in the serum suppresses the growth of murine and human tumors in vivo.
abstract: Previously we have hypothesized that the small molecules which are selectively accumulated in cancer cells might participate in a non-immunological antitumor surveillance mechanism. We demonstrated earlier that a mixture of experimentally selected substances ("active mixture", AM: L-arginine, L-histidine, L-methionine, L-phenylalanine, L-tyrosine, L-tryptophan, L-ascorbate, D-biotin, pyridoxine, riboflavin, adenine, L(-)malate) possesses a selective toxic effect in vitro on a variety of tumor cell lines, and we have shown that the AM selectively induces apoptosis of cancer cells in vitro. To explore the in vivo significance of our earlier findings we examined the antitumor effect of AM in Colon 26 murine colorectal adenocarcinoma, B16 murine melanoma, MXT murine mammary carcinoma, S180 murine sarcoma, P388 murine lymphoid leukemia, HL-60 human promyeloid leukemia, PC-3 human prostate carcinoma, and HT-29 human colon carcinoma tumor models. Treatment of tumor bearing mice with AM inhibited the growth of the tumors investigated, with an inhibitory effect ranging from 40 to 69%. The AM had a comparable antitumor effect with 5-fluorouracil and cisplatin in the Colon-26 tumor model, and combined treatment with AM and 5-fluorouracil or cisplatin resulted in an enhanced tumor growth inhibitory effect. The AM induced apoptosis through the mitochondrial pathway and induced G1 arrest in PC-3 cells and increased the number of apoptotic cells in PC-3 xenografts. These findings suggest that the AM might offer an interesting perspective in the treatment of cancer and in combination with other treatments may offer hope for a more effective cancer therapy.
authors.affiliation: Immunal Ltd., Cancer Research and Product Development Laboratory, H-7630 Pécs, Finn u. 1/1., Hungary. kulcsar@immunal.hu
authors.forename: Gyula
authors.initials: G
authors.lastname: Kulcsár
authors.forename: Dezső
authors.initials: D
authors.lastname: Gaál
authors.forename: Péter I
authors.initials: PI
authors.lastname: Kulcsár
authors.forename: Ákos
authors.initials: Á
authors.lastname: Schulcz
authors.forename: Tamás
authors.initials: T
authors.lastname: Czömpöly
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage; D016193:G1 Phase / Q000187:drug effects; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D007941:Leukemia P388; D008546:Melanoma, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000596:Amino Acids; D053453:Caspase 9; D002945:Cisplatin; D005472:Fluorouracil