title: Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide.
abstract: The use of a mixture of amino acids caused a selective apoptosis induction against a variety of tumor cell lines, reduced the adverse effects of anti-cancer drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects and underlying mechanisms of soy-derived multiple amino acids' oral supplementation on the therapeutic efficacy of low-dose cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180) cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived multiple amino acid supplement indicated that the soy-derived multiple amino acid supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl-2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar responses as CTX plus soy-derived multiple amino acid in downregulating autophagy and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived multiple amino acid supplement had a potent anti-tumor effect mediated through downregulation of autophagy and upregulation of apoptosis.
authors.affiliation: Department of Life Science, No. 88, Sec. 4, Tingzhou Road, National Taiwan Normal University, Taipei 11677, Taiwan. yaoc1589@ntuh.gov.tw.|Department of Family Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. yaoc1589@ntuh.gov.tw.
authors.forename: Chien-An
authors.initials: CA
authors.lastname: Yao
authors.affiliation: Biotechnology Center, Grape King Inc., Chung-Li 320, Taiwan. nchinchu@gmail.com.
authors.forename: Chin-Chu
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Orthopedic, Kuang-Tien General Hospital, Taichung 433, Taiwan. npwang@ktgh.com.tw.
authors.forename: Nai-Phog
authors.initials: NP
authors.lastname: Wang
authors.affiliation: Department of Life Science, No. 88, Sec. 4, Tingzhou Road, National Taiwan Normal University, Taipei 11677, Taiwan. ctchien@ntnu.edu.tw.
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
mesh_terms: D000284:Administration, Oral; D000596:Amino Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008928:Mitochondria / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D012509:Sarcoma / Q000188:drug therapy*; D013025:Glycine max / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide
keywords: Atg5; apoptosis; autophagy; chemotherapy; mice; soy-based amino acids