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.

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“…The signal was visualized by incubation with liquid diaminobenzidine tetrahydrochloride. TUNEL staining was used to measure DNA fragmentation in deparaffinized, fixed sections according to the manufacturer's protocol (FragEL DNA Fragmentation kit, Calbiochem), and the resulting sections were visualized by fluorescence microscopy [ 53 ]. For quantification, TUNEL-positive nuclei were counted in 5 randomly selected high-power (400EL fields, and an average was determined for each section.…”

Correction: Yao, C.A., et al. Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide. Nutrients 2016, 8, 192

“…The authors wish to make the following correction to their published paper [ 1 ]. The second from the left panel (D 0.5) in Figure 5 B is overlayed with the leftmost image (D 0.0).…”