Mistletoe extract Fraxini inhibits the proliferation of liver cancer by down-regulating c-Myc expression
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Published on: March 1, 2022
Peiying Yang1, Yan Jiang2, Yong Pan2
1Departments of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. pyang@mdanderson.org.
Abstract:
Mistletoe (Viscum album) is a type of parasitic plant reported to have anticancer activity including in hepatocellular carcinoma (HCC). However, the mechanism of mistletoe's anticancer activity, and its effectiveness in treating HCC are not fully understood. We report here that mistletoe extracts, including Fraxini (grown on ash trees) and Iscador Q and M (grown on oak and maple trees), exert strong antiproliferative activity in Hep3B cells, with median inhibitory concentrations (IC50) of 0.5 µg/mL, 7.49 µg/mL, and 7.51 µg/mL, respectively. Results of Reversed Phase Proteomic Array analysis (RPPA) suggests that Fraxini substantially down-regulates c-Myc expression in Hep3B cells. Fraxini-induced growth inhibition (at a concentration of 1.25 μg/ml) was less pronounced in c-Myc knockdown Hep3B cells than in control cells. Furthermore, in the Hep3B xenograft model, Fraxini-treated (8 mg/kg body weight) mice had significantly smaller tumors (34.6 ± 11.9 mm3) than control mice (161.6 ± 79.4 mm3, p < 0.036). Similarly, c-Myc protein expression was reduced in Fraxini treated Hep3B cell xenografts compared to that of control mice. The reduction of c-Myc protein levels in vitro Hep3B cells appears to be mediated by the ubiquitin-proteasome system. Our results suggest the importance of c-Myc in Fraxini's antiproliferative activity, which warrants further investigation.
Insights
Mistletoe extract Fraxini shows anticancer effects against hepatocellular carcinoma (HCC) by reducing c-Myc expression. This parasitic plant extract significantly inhibited tumor growth in mice, highlighting its therapeutic potential.
Area of Science:
- Phytochemistry
- Oncology
- Molecular Biology
Background:
- Mistletoe (Viscum album) is recognized for potential anticancer properties, particularly in hepatocellular carcinoma (HCC).
- The precise mechanisms and efficacy of mistletoe in HCC treatment remain incompletely understood.
- Specific mistletoe extracts, including Fraxini, Iscador Q, and Iscador M, are investigated for their biological activities.
Purpose of the Study:
- To investigate the antiproliferative effects of mistletoe extracts on hepatocellular carcinoma (HCC) cells.
- To elucidate the role of c-Myc in the anticancer activity of mistletoe extract Fraxini.
- To evaluate the in vivo efficacy of Fraxini in a HCC xenograft model.
Main Methods:
- In vitro antiproliferative assays using Hep3B cells treated with mistletoe extracts (Fraxini, Iscador Q, Iscador M).
- Reversed Phase Proteomic Array (RPPA) analysis to assess c-Myc expression.
- c-Myc knockdown experiments in Hep3B cells.
- In vivo studies using a Hep3B xenograft mouse model treated with Fraxini.
- Analysis of c-Myc protein levels in xenograft tumors.
Main Results:
- Mistletoe extracts Fraxini, Iscador Q, and Iscador M demonstrated significant antiproliferative activity against Hep3B cells.
- Fraxini extract markedly down-regulated c-Myc expression in Hep3B cells, as indicated by RPPA.
- Fraxini's growth-inhibitory effect was diminished in c-Myc knockdown cells, suggesting c-Myc's involvement.
- In vivo, Fraxini treatment significantly reduced tumor volume in the Hep3B xenograft model compared to controls.
- Reduced c-Myc protein expression was observed in Fraxini-treated xenografts, correlating with tumor growth inhibition.
Conclusions:
- Mistletoe extract Fraxini exhibits potent antiproliferative activity against HCC cells, partly mediated by the down-regulation of c-Myc.
- The ubiquitin-proteasome system appears to be involved in the reduction of c-Myc protein levels by Fraxini in vitro.
- Fraxini demonstrates therapeutic potential for HCC treatment, warranting further investigation into its mechanisms and clinical application.
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