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Article

Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway

  • Authors:
    • Siying Li
    • Guang Yang
    • Xiaosong Zhu
    • Lin Cheng
    • Yueyue Sun
    • Zhongxi Zhao
  • View Affiliations / Copyright

    Affiliations: School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Endocrinology, Heze Municipal Hospital, Heze, Shandong 274000, P.R. China
  • Pages: 1637-1644
    |
    Published online on: July 24, 2017
       https://doi.org/10.3892/or.2017.5849
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Abstract

The natural plant-derived product S-allylmercapto­cysteine (SAMC) has been studied in cancer therapy as a single and combination chemotherapeutic agent. The present study was employed to verify the combination use of SAMC and rapamycin that is the mTOR inhibitor with anticancer ability but has limited efficacy due to drug resistance, and to explore the underlying mechanisms. We combined rapamycin and SAMC for colorectal cancer treatment in the HCT‑116 cancer cells and a xenograft murine model. The in vivo study was established by xenografting HCT‑116 cells in BALB/c nude mice. It was found that the combination therapy had enhanced tumor-suppressing ability with the upregulation of the Bax/Bcl-2 ratio as a consequence of activated apoptosis, inhibition of autophagic activity and prevention of Akt phosphorylation. The rapamycin and SAMC combination activated antioxidant transcription expressions of Nrf2 and downstream gene NQO1. Concomitantly, autophagosome cargo p62 was downregulated, indicating that the p62 played a negative-regulatory role between Nrf2 and autophagy. Our results show that the combination of SAMC and rapamycin enhanced the anticancer ability, which could be used for the treatment of colorectal cancer. The underling mechanism of autophagy/p62/Nrf2 pathway discovered may provide a new direction for drug development, especially for traditional Chinese medicines.
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Copy and paste a formatted citation
Spandidos Publications style
Li S, Yang G, Zhu X, Cheng L, Sun Y and Zhao Z: Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway. Oncol Rep 38: 1637-1644, 2017.
APA
Li, S., Yang, G., Zhu, X., Cheng, L., Sun, Y., & Zhao, Z. (2017). Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway. Oncology Reports, 38, 1637-1644. https://doi.org/10.3892/or.2017.5849
MLA
Li, S., Yang, G., Zhu, X., Cheng, L., Sun, Y., Zhao, Z."Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway". Oncology Reports 38.3 (2017): 1637-1644.
Chicago
Li, S., Yang, G., Zhu, X., Cheng, L., Sun, Y., Zhao, Z."Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway". Oncology Reports 38, no. 3 (2017): 1637-1644. https://doi.org/10.3892/or.2017.5849
Copy and paste a formatted citation
x
Spandidos Publications style
Li S, Yang G, Zhu X, Cheng L, Sun Y and Zhao Z: Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway. Oncol Rep 38: 1637-1644, 2017.
APA
Li, S., Yang, G., Zhu, X., Cheng, L., Sun, Y., & Zhao, Z. (2017). Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway. Oncology Reports, 38, 1637-1644. https://doi.org/10.3892/or.2017.5849
MLA
Li, S., Yang, G., Zhu, X., Cheng, L., Sun, Y., Zhao, Z."Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway". Oncology Reports 38.3 (2017): 1637-1644.
Chicago
Li, S., Yang, G., Zhu, X., Cheng, L., Sun, Y., Zhao, Z."Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway". Oncology Reports 38, no. 3 (2017): 1637-1644. https://doi.org/10.3892/or.2017.5849
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