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A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
Published on: November 28, 2014
Trichosanthin increases Granzyme B penetration into tumor cells by upregulation of CI-MPR on the cell surface
Chunman Li1, Meiqi Zeng1, Huju Chi1
1Department of Anatomy, Histology and Developmental Biology, School of Basic Medical Sciences, Shenzhen University Health Science Centre, Shenzhen, Guangdong, China.
Abstract:
Trichosanthin is a plant toxin belonging to the family of ribosome-inactivating proteins. It has various biological and pharmacological activities, including anti-tumor and immunoregulatory effects. In this study, we explored the potential medicinal applications of trichosanthin in cancer immunotherapy. We found that trichosanthin and cation-independent mannose-6-phosphate receptor competitively bind to the Golgi-localized, γ-ear containing and Arf-binding proteins. It in turn promotes the translocation of cation-independent mannose-6-phosphate receptor from the cytosol to the plasma membrane, which is a receptor of Granzyme B. The upregulation of this receptor on the tumor cell surface increased the cell permeability to Granzyme B, and the latter is one of the major factors of cytotoxic T lymphocyte-mediated tumor cell apoptosis. These results suggest a novel potential application of trichosanthin and shed light on its anti-tumor immunotherapy.
Insights
Trichosanthin enhances cancer immunotherapy by promoting Granzyme B entry into tumor cells. This plant toxin upregulates a key receptor, increasing cancer cell apoptosis via cytotoxic T lymphocytes.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Trichosanthin, a ribosome-inactivating protein, exhibits anti-tumor and immunoregulatory properties.
- Its precise mechanisms in cancer immunotherapy remain largely unexplored.
Purpose of the Study:
- To investigate the potential of trichosanthin in cancer immunotherapy.
- To elucidate the molecular mechanisms underlying trichosanthin's anti-tumor effects.
Main Methods:
- Investigated the interaction between trichosanthin and cation-independent mannose-6-phosphate receptor (CI-M6PR).
- Analyzed the translocation of CI-M6PR from the cytosol to the plasma membrane.
- Assessed the impact on tumor cell permeability to Granzyme B.
Main Results:
- Trichosanthin competitively binds to Golgi-localized proteins with CI-M6PR.
- This binding promotes CI-M6PR translocation to the plasma membrane, a Granzyme B receptor.
- Upregulation of CI-M6PR enhances tumor cell permeability to Granzyme B, inducing apoptosis.
Conclusions:
- Trichosanthin shows potential as a novel agent in cancer immunotherapy.
- The findings reveal a new mechanism for trichosanthin's anti-tumor activity involving Granzyme B-mediated apoptosis.
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