Soy-based multiple amino acid oral supplementation increases the anti-sarcoma effect of cyclophosphamide
Journal
Nutrients
Journal Volume
8
Journal Issue
4
Date Issued
2016
Author(s)
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. ? 2016 by the authors; licensee MDPI, Basel, Switzerland.
Subjects
Apoptosis; Atg5; Autophagy; Chemotherapy; Mice; Soy-based amino acids
SDGs
Other Subjects
3 methyladenine; alanine; amino acid; arginine; aspartic acid; autophagy protein 5; caspase 3; cyclophosphamide; cystine; glutamic acid; glycine; histidine; isoleucine; leucine; lysine; methionine; phenylalanine; proline; protein Bax; protein bcl 2; serine; soy derived multiple amino acid; threonine; tyrosine; unclassified drug; valine; alkylating agent; amino acid; cyclophosphamide; animal cell; animal model; animal tissue; antineoplastic activity; apoptosis; Article; autophagy; controlled study; diet supplementation; DNA sequence; gene silencing; growth inhibition; immune deficiency; immunohistochemistry; low drug dose; male; mouse; nonhuman; protein expression; sarcoma; soybean; tumor growth; tumor volume; TUNEL assay; Western blotting; animal; chemistry; dietary supplement; dose response; drug effects; drug potentiation; gene expression regulation; human; mitochondrion; Neoplasms, Experimental; oral drug administration; sarcoma; SCID mouse; Administration, Oral; Amino Acids; Animals; Antineoplastic Agents, Alkylating; Cyclophosphamide; Dietary Supplements; Dose-Response Relationship, Drug; Drug Synergism; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, SCID; Mitochondria; Neoplasms, Experimental; Sarcoma; Soybeans
Publisher
MDPI AG
Type
journal article