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Nutrients 2016, 8(4), 192; doi:10.3390/nu8040192

Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide

1
Department of Life Science, No. 88, Sec. 4, Tingzhou Road, National Taiwan Normal University, Taipei 11677, Taiwan
2
Department of Family Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
3
Biotechnology Center, Grape King Inc., Chung-Li 320, Taiwan
4
Department of Orthopedic, Kuang-Tien General Hospital, Taichung 433, Taiwan
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 10 February 2016 / Revised: 8 March 2016 / Accepted: 22 March 2016 / Published: 1 April 2016
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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. View Full-Text
Keywords: apoptosis; autophagy; Atg5; soy-based amino acids; chemotherapy; mice apoptosis; autophagy; Atg5; soy-based amino acids; chemotherapy; mice
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Yao, C.-A.; Chen, C.-C.; Wang, N.-P.; Chien, C.-T. Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide. Nutrients 2016, 8, 192.

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