Systems Pharmacology-Based Dissection of Anti-Cancer Mechanism of Traditional Chinese Herb Saussurea involucrata.

Qian Zhang,Xue Ying,Dehua Kong,Hongqing Zhu,Lanyu He,Qingqing Jiang,Hua Zhang,Zhiqiang Cheng,Yaxin Zheng,Hongtao Deng

doi:10.3389/fphar.2021.678203

Abstract

Cancer has the highest mortality in humans worldwide, and the development of effective drugs remains a key issue. Traditional Chinese medicine Saussurea involucrata (SI) exhibits a series of effects, such as anti-cancer, but the action mechanisms are still unclear. Here, systems pharmacology was applied to reveal its anti-cancer mechanism. First, we screened the active compounds of SI. Then, the compound–target network, target–disease network, and target–pathway network were constructed. DAVID was applied for GOBP analysis and KEGG pathway enrichment analysis on cancer-related targets. Seven potential compounds and 187 targets were identified. The target–disease classification network showed that compounds mainly regulated proteins related to cancer, nervous system diseases, and cardiovascular system diseases. Also, SI anti-tumor effect mainly associated with the regulation of NO production, angiogenesis, MAPK, and PKB from GOBP enrichment. Additionally, KEGG pathway enrichment indicated that targets involved in anti-inflammatory action, inhibiting angiogenesis and anti-proliferation or inducing apoptosis. Experimental validation showed that four active compounds could inhibit cell proliferation and promote apoptosis in A549 (except for kaempferol), PC-3, and C6 cells. This study not only provides experimental evidence for further research on SI in cancer treatment but also promotes the development of potential drugs of SI in modern medicine.

Highlights

Cancer has become one of the major diseases that threaten human health globally (Siegel et al, 2020) and brought a huge economic burden to the world until now
Compounds’ targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and UniProt was used to query target information (Supplementary Table S1)
Seven active compounds and 187 related targets were obtained under the conditions of drug likeness and oral bioavailability based on systems pharmacology

Summary

Introduction

Cancer has become one of the major diseases that threaten human health globally (Siegel et al, 2020) and brought a huge economic burden to the world until now. As one of the main methods, chemotherapy is indispensable in cancer treatment, but the serious adverse effects of chemotherapeutic drugs limit its further development and application (Zhai et al, 2019). Facing such situations, it is urgently necessary to explore effective drugs and study new therapies. Traditional Chinese medicine (TCM) is rich in various chemical components and can regulate multiple cancer-related signaling pathways and targets. It has the advantages of alleviating side effects, providing high safety, and prolonging the survival time of patients It is increasingly beneficial to apply TCM for cancer treatment

Methods

Results

Discussion

Conclusion