Cucurbitacin E Inhibits Huh7 Hepatoma Carcinoma Cell Proliferation and Metastasis via Suppressing MAPKs and JAK/STAT3 Pathways.

Yang Liu,Kewu Zeng,Mingbo Zhao,Tingting Liu,Pengfei Tu,Heng Yang,Qiang Guo,Yong Jiang

doi:10.3390/molecules25030560

Abstract

Cucurbitacin E (CuE), a highly oxygenated tetracyclic triterpene from Cucurbitaceae, has shown to exhibit potent cytotoxic and anti-proliferative properties against several human cancer cells. However, the underlying effects and mechanisms of CuE regarding hepatocellular carcinoma (HCC) have not been well understood. In the current study, unbiased RNA-sequencing (RNA-seq) and bioinformatics analysis was applied to elucidate the underlying molecular mechanism. CuE could significantly inhibit cell proliferation and migration of Huh7 cells, meanwhile CuE exhibited potent anti-angiogenic activity. RNA-seq analysis revealed that CuE negatively regulated 241 differentially expressed genes (DEGs) involved in multiple processes including cytoskeleton formation, angiogenesis and focal adhesion. Further analysis revealed that CuE effectually regulated diversified pharmacological signaling pathways such as MAPKs and JAK-STAT3. Our findings demonstrated the role of CuE in inhibiting proliferation and migration, providing an insight into the regulation of multiple signaling pathways as a new paradigm for anti-cancer treatment strategy.

Highlights

Hepatocellular carcinoma (HCC) is reported to be the most common cancer and aggressive human malignancies worldwide [1,2,3]
We found that Cucurbitacin E (CuE) could significantly inhibit the proliferation and migration of
Our findings show that CuE is a promising drug candidate for inhibiting cancer cell proliferation and migration, which suggests a crucial therapeutic strategy by targeting multiple signaling pathways for HCC

Summary

Introduction

Hepatocellular carcinoma (HCC) is reported to be the most common cancer and aggressive human malignancies worldwide [1,2,3]. Cancer development is a multi-step process that arises from a series of genetic and epigenetic events leading to multiple alterations in signaling pathways, such as the growth factor pathway, VEGF pathway, MAPK, and JAK/STAT pathway [6,7]. Targeting these signaling pathways has been considered a promising strategy for cancer therapy. It is difficult to achieve the desired therapeutic effect by using single target therapy For these situations, discovery of molecules that target multiple proteins or signaling pathways involved in HCC may be a more effective therapeutic strategy [10,11,12]

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Conclusion