An example of toxic medicine used in Traditional Chinese Medicine for cancer treatment

An interesting paper “Toxicmedicine used in Traditional Chinese Medicine for cancer treatment: are ion channels involved?”¹ was published in the Journal of Traditional Chinese Medicine on August 17 this year. This paper proposed a unique view of the potential role of ion channels in the pharmacological effects of toxic Traditional Chinese Medicine (TCM) for cancer. However, the paper generally introduced the topic without a specific example. This letter provided an example of toxic medicine used in TCM for cancer treatment and conducted a TCM network analysis of scorpion medicine for glioma treatment.

Scorpion or extract from scorpion has been frequently used for clinical cancer treatment. For glioma, the scorpion is one of the most frequently used TCM in cancer medications and it is thought to affect tumors via ion channels. However, the exact targets of scorpion medications for glioma have not been studied systematically. Bioinformatic analysis has been wildly used for cancer biomarker and targets studies.^2,⇓,⇓-5 The study in this letter identified ion channel-related targets of the scorpion by an intersection analysis between the ion channel gene list (downloaded from the Genecards with the search term “ion channel”), scorpion target gene list (predicted by the BATMAN-TCM), and glioma related gene list (downloaded from the Genecards with the search term “glioma”). The chemical constituents of scorpion used to predict scorpion targets by BATMAN-TCM included Trimethylamine Oxide, Cholesteryl Ferulate, Cholesterol, Taurine, Stearin, 20-Hexadecanoylingenol, and Trimethylamine. Using data from the TCGA LGG + GBM cohort, this study then analyzed the survival association and expression of these targets in glioma. Based on these analyses, this study identified glioma-critical ion channel-related targets of the scorpion to construct a protein-protein interaction network.

The intersection analysis between the ion channel-related gene list and the scorpion target gene list identified 51 genes as the ion channel-related targets of the scorpion for glioma (Figure 1A). The expression analysis revealed that 50 of the 51 genes were significantly expressed aberrantly in glioma compared to normal brain tissues (Figure 1B). The survival analysis revealed that 44 genes were associated with the survival of glioma and were defined as critical ion channel-related targets of the scorpion in glioma. Among these genes, 18 genes were associated with better survival (Figure 1C) and 26 genes were associated with worse survival (Figure 1D). Based on these genes, this study constructed a geneontology and Kyoto ency-clopedia of genes and genomes enrichment analysis (Figure 2A) and protein-protein interaction network (Figure 2B) of critical ion channel-related targets of the scorpion in glioma for future reference.

Figure 1. Identification of ion channel related scorpion targets for glioma treatment.

A: intersection analysis; B: expression of the targets in glioma and normal brain tissues; C: protective targets (better survival); D: risky targets (worse survival). Only the top 20 genes were listed in the forest plot.

Figure 2. The enrichment and network analysis of scorpion for glioma treatment.

A: geneontology (GO) and Kyoto ency-clopedia of genes and genomes (KEGG) enrichment; B: protein-protein interaction network of critical ion channel-related targets of the scorpion in glioma.

Therefore, this study concluded that the critical ion channel-related targets of the scorpion in glioma are potential therapeutic targets of toxic TCM scorpion toward glioma. However, this study is a pilot study for the effects of scorpion medicine on glioma, more experimental-based evidence is required to further validate the targets identified by this study in the future. Nevertheless, this letter provides a classical example of toxic medicine used in TCM for cancer treatment and as an instrumental supplementary for the previously published paper.