2. Academic Validation
  3. Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular Carcinoma

Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular Carcinoma

  • Int J Mol Sci. 2023 Jan 11;24(2):1416. doi: 10.3390/ijms24021416.
Kaifang Wang 1 2,  Xiaona Wang 3,  Minghuan Zhang 3,  Zhenguang Ying 1,  Zeyao Zhu 4,  Kin Yip Tam 5,  Chunman Li 6,  Guowei Zhou 3,  Feng Gao 1,  Meiqi Zeng 1,  Stephen Cho Wing Sze 2,  Xia Wang 3,  Ou Sha 1
Affiliations

Affiliations

  • 1 School of Dentistry, Shenzhen University Medical School, Shenzhen 518000, China.
  • 2 Department of Biology, Faculty of Science, Hong Kong Baptist University, Hongkong 999077, China.
  • 3 Department of Anatomy and Histology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen 518000, China.
  • 4 Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518000, China.
  • 5 Faculty of Health Sciences, University of Macau, Macau, China.
  • 6 Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515000, China.
PMID: 36674931 DOI: 10.3390/ijms24021416
Abstract

Trichosanthin (TCS) is a type I ribosome-inactivating protein extracted from the tuberous root of the plant Trichosanthes. TCS shows promising potential in clinical drug abortion, anti-tumor and immunological regulation. However, the molecular mechanisms of its anti-tumor and immune regulation properties are still not well discovered. In the present study, we investigated the anti-tumor activity of TCS in hepatocellular carcinoma (HCC), both in vitro and in vivo. Both HCC cell lines and xenograft tumor tissues showed considerable growth inhibition after they were treated with TCS. TCS provoked caspase-mediated Apoptosis in HCC cells and xenograft tumor tissues. The recruitment of CD8+ T cells to HCC tissues and the expression of chemokines, CCL2 and CCL22, were promoted upon TCS treatment. In addition, TCS induced an upregulation of Granzyme B (GrzB), TNF-α and IFN-γ in HCC tissues, which are the major cytotoxic mediators produced by T cells. Furthermore, TCS also resulted in an increase of mannose-6-phosphate receptor (M6PR), the major receptor of GrzB, in HCC tissues. In summary, these results suggest that TCS perhaps increases T-cell immunity via promoting the secretion of chemokines and accelerating the entry of GrzB to HCC cells, which highlights the potential role of TCS in anti-tumor immunotherapy.

Keywords

Granzyme B (GrzB); T cell; Trichosanthin (TCS); apoptosis; chemokine; hepatocellular carcinoma (HCC).

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