TY - JOUR
T1 - Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular Carcinoma
AU - Wang, Kaifang
AU - Wang, Xiaona
AU - Zhang, Minghuan
AU - Ying, Zhenguang
AU - Zhu, Zeyao
AU - Tam, Kin Yip
AU - Li, Chunman
AU - Zhou, Guowei
AU - Gao, Feng
AU - Zeng, Meiqi
AU - Sze, Stephen Cho Wing
AU - Wang, Xia
AU - Sha, Ou
N1 - This study was financially supported by the National Natural Science Foundation of China (81773939) and the Technology Foundation of Shenzhen City (JCYJ20210324094005015).
Sonal Mishra is thankful to University Grants Commission (UGC), New Delhi, India, for the financial assistance in the form of a fellowship as Senior Research Fellow (Joint CSIR-UGC, NTA Ref. No.: 191620046790). Amit Gupta (09/013(0912)/2019-EMR-I) is thankful to the Council of Scientific & Industrial Research (CSIR), New Delhi, India, for the Senior Research Fellowship (SRF).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/1/11
Y1 - 2023/1/11
N2 - 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.
AB - 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.
KW - apoptosis
KW - chemokine
KW - Granzyme B (GrzB)
KW - hepatocellular carcinoma (HCC)
KW - T cell
KW - Trichosanthin (TCS)
UR - http://www.scopus.com/inward/record.url?scp=85146515307&partnerID=8YFLogxK
U2 - 10.3390/ijms24021416
DO - 10.3390/ijms24021416
M3 - Journal article
C2 - 36674931
AN - SCOPUS:85146515307
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 2
M1 - 1416
ER -