Trichosanthin cooperates with Granzyme B to restrain tumor formation in tongue squamous cell carcinoma

Abstract

Background Tongue squamous cell carcinoma (TSCC) is a common type of oral cancer, with a relatively poor prognosis and low post-treatment survival rate. Various strategies and novel drugs to treat TSCC are emerging and under investigation. Trichosanthin (TCS), extracted from the root tubers of Tian-Hua-Fen, has been found to have multiple biological and pharmacological functions, including inhibiting the growth of cancer cells. Granzyme B (GrzB) is a common toxic protein secreted by natural killer cells and cytotoxic T cells. Our group has reported that TCS combined with GrzB might be a superior approach to inhibit liver tumor progression, but data relating to the use of this combination to treat TSCC remain limited. The aim of this study was to examine the effectiveness of TCS on TSCC processes and underlying mechanisms. Methods First, we screened the potential antitumor activity of TCS using two types of SCC cell lines. Subsequently, a subcutaneous squamous cell carcinoma xenograft model in nude mice was established. These model mice were randomly divided into four groups and treated as follows: control group, TCS treatment group, GrzB treatment group, and TCS/GrzB combination treatment group. Various tumorigenesis parameters, such as Ki67, PCNA, caspase-3, Bcl-2 and VEGFA, et al., were performed to determine the effects of these treatments on tumor development. Results Screening confirmed that the SCC25 line exhibited greater sensitivity than the SCC15 line to TCS in vitro studies. TCS or GrzB treatment significantly inhibited tumor growth compared with the inhibition seen in the control group. The TCS/GrzB combination inhibited tumor growth more than either drug alone. TCS treatment inhibited tumor proliferation by downregulating Ki67 and Bcl2 protein expression while accelerating tumor apoptosis. In the TCS/GrzB-treated group, expression of Ki67 was further downregulated, while the level of activated caspase-3 was increased, compared with their expression in either of the single drug treatment groups. Conclusion These results suggest that the TCS/GrzB combination could represent an effective immunotherapy for TSCC.

Nodal Disease and Survival in Oral Cancer: Is Occult Metastasis a Burden Factor Compared to Preoperatively Nodal Positive Neck?

“…Sensitivities of 64% to 93% for presurgical magnetic resonance imaging (MRI) and of 66% to 85% for presurgical computed tomography (CT) have been reported in the detection of cervical lymph node metastasis [ 4 ]. Although, in a meta-analysis from Sun et al, 2022, better sensitivity and specificity was found for the MRI than the CT [ 5 ], other studies show similar sensitivity rates for both MRI and CT [ 6 ]. Relatively high sensitivity (75% to 90%) and specificity (94% to 99%) are reported in detecting lymph node metastases with 8F-fluorodeoxyglucose positron emission tomography (18FDG-PET) [ 7 ].…”

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

“…Apoptosis and autophagy are common modes of tumor cell death [ 25 , 26 ]. It has been reported that TCS can promote the death of Oral squamous cell carcinoma SCC25 by inducing cell apoptosis [ 9 ]. In order to better understand the mechanisms of TCS-induced cell death, HCC cells were treated with 25 μg/mL TCS, total protein was extracted and the expression levels of apoptosis- and autophagy-related proteins were detected by Western blot.…”

“…TCS is the major active ingredient of Trichosanthes Kirilowii [ 36 ]. Previous studies reported TCS alone showed an excellent inhibitory effect on cancer cell proliferation in vitro [ 9 , 23 , 37 ]. However, TCS alone had not significantly inhibited tumor growth in immunodeficient nude mice in vivo [ 23 ].…”

“…Trichosanthin (TCS), a single-chain ribosome-inactivating protein extracted from the tuberous root of the traditional Chinese herb Trichosanthes , exhibits prospective application in clinical drug abortion, anti-virus, anti-tumor and immune regulation [ 8 ]. Numerous studies have shown that TCS could directly inhibit the proliferation and apoptosis of cancer cells by regulating the expression of Bcl-2 [ 9 ], inducing S-phase cell cycle arrest in cancer cells [ 10 ], inhibiting tumor dysplasia-related signaling pathways [ 11 ], increasing the expression or activation of caspase family proteins [ 12 , 13 , 14 ], etc. In physiological conditions, TCS could regulate the immune status of the body by regulating the CD4 + /CD8 + T-cell ratio and producing related immune cytokines in peripheral blood [ 15 ].…”

Cocktail of Astragalus Membranaceus and Radix Trichosanthis Suppresses Melanoma Tumor Growth and Cell Migration Through Regulation of Akt-Related Signaling Pathway

“…Astragalus Membranaceus (AM) and Radix Trichosanthis (RT) are two herbs widely used in TCM to treat different cancers, which have been proven to inhibit tumor growth and metastasis ( Zhu et al, 2021 ; Bian et al, 2022 ). Chinese herbal compound formula is used most commonly in the clinic, and it is more effective when certain specific herbs and certain ratios are used together.…”