Eupatilin regulates proliferation and cell cycle of cervical cancer by regulating hedgehog signalling pathway

Abstract

Eupatilin (5,7-dihydroxy-3 0 ,4 0 ,6-trimethoxyflavone) is a natural active substance found in génépi group plants, and its pharmacological activities has been proven to be useful in the treatment of various cancers. However, whether eupatilin demonstrates anti-cancer activity in cervical cancer is still under evaluation. To clarify this, cancer cell lines and nude mouse model were used in this study. The results indicated that eupatilin could inhibit the occurrence of cervical cancer both in vivo and in vitro.Cervical cancer cell lines (C4-1, HeLa, Caski, and Siha) and Ect1/E6E7 cells were incubated with eupatilin (40μM) for 48 hours. Compared with the control group, the viability of cervical cancer cells decreased significantly, while the apoptotic cells increased significantly. Cell cycle analysis showed that eupatilin treatment of HeLa and Caski cells reduced the proliferation index. Eupatilin at 40 mg/kg also inhibited tumour growth in tumour-bearing mice. Interestingly, weakened hedgehog signalling was observed in cervical cancer cells and tumours from tumour-bearing mice after eupatilin treatment. Our results reveal the inhibitory effect of eupatilin on cervical cancer and shed new light on the molecular mechanism of its therapeutic effect.

Eupatilin Promotes Cell Death by Calcium Influx through ER-Mitochondria Axis with SERPINB11 Inhibition in Epithelial Ovarian Cancer

“…In this study, it was confirmed that the mechanism of action of eupatilin previously reported in other cancer cells can be applied to ovarian cancer cells, along with the discovery of newly identified physiological mechanisms and target proteins of eupatilin. Even recently, it has been suggested that eupatilin may have therapeutic effects in cancers derived from female reproductive organs, such as cervical cancer [29]. Furthermore, Jurkat T-cell immune suppression was induced by eupatilin-mediated calcium oscillation and NF-κB inhibition, which is a primary aspect of the pharmacological activity of eupatilin [30].…”

Tetramethylpyrazine inhibits the proliferation, invasiveness and migration of cervical cancer C33A cells by retarding the Hedgehog signaling pathway

“…A previous study demonstrated that TMP disrupted the Hh signaling pathway to reduce sinusoidal tubule angiogenesis, and to inhibit the angiogenic properties of liver sinusoidal endothelial cells (32). Another study reported that a compound extracted from Artemisia plants reduced the proliferative index of HeLa and Caski CC cells through the Hh signaling pathway, and inhibited tumor growth in tumor-bearing mice (33). Furthermore, sonic Hh gene silencing has been demonstrated to inhibit the epithelial-mesenchymal transition, as well as the proliferation, invasiveness and migration of CC cells by inhibiting the Hh signaling pathway (34).…”

Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer

“…Deregulation of the cell cycle represents an important trait of tumors ( Yu et al, 2020 ). Many anti-cancer drugs inhibit tumor cell proliferation via stalling the cell cycle ( Wu et al, 2020 ). Cos was found to induce G1/S phase arrest in human esophageal carcinoma Eca-109 cells ( Hua et al, 2016b ) and induce G2/M phase arrest in human liver cancer HepG2 cells and breast cancer MDA-MB-231 cells ( Mao et al, 2019 ).…”

“…One study reported that it suppresses gastric cancer by repressing AKT/GSK3β signaling to inhibit autophagy ( Dai et al, 2021 ). Another reported placenta-specific 8 inhibited oral squamous cell carcinogenesis via blocking AKT/GSK3β signaling pathways ( Wu et al, 2020 ). This study confirmed the inhibitory effects of Cos on the AKT/GSK3β pathway, which was reversed by SC79 (AKT activator) pretreatment.…”