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Morusin exerts anti-cancer activity in renal cell carcinoma by disturbing MAPK signaling pathways
Chengfei Yang1, Jing Luo1, Xing Luo1
1Department of Urology, Second Affiliated Hospital, Army Military Medical University, Chongqing 400037, China.
Background:
Renal cell carcinoma (RCC) has gradually become a severe type of kidney malignant tumor, which warrants an urgent need for highly efficacious therapeutic agents. Morusin, a typical prenylated flavonoid, has been revealed to possess anticarcinogenic effects against several cancers by inhibiting cell proliferation and tumorigenesis.
Methods:
Cells proliferation was examined by CCK-8. Migration assays were performed using a 24-well transwell chamber. Apoptotic cells were detected using the Annexin V PE/7-AAD apoptosis detection kit. Cell cycle analysis was carried out by flow cytometry. Western blotting and quantitative real time (qRT) PCR were used to exam the change of target gene in mRNA and protein level. Nude mouse xenograft experiments were performed to identify vivo function of morusin.
Results:
Here, we evaluated the effect of morusin against RCC. We treated three RCC cell lines, 769-P, 786-O, and OSRC-2, with morusin to study its effects on cell growth, migration, apoptosis, cell cycle and cancer-related pathways. Additionally, we assessed the effects of morusin on tumor growth using a nude mouse model. Morusin could inhibit cell growth and migration, induce cell apoptosis and downregulate apoptosis-related proteins, and disturb the cell cycle arrest in the G1 phase. Additionally, morusin could suppress RCC tumorigenesis in vivo. Moreover, mitogen-activated protein kinase (MAPK) signal pathways were found to be involved in morusin-induced anti-cancer activity. P-p38 and P-JNK levels were up-regulated by morusin, while the ERK phosphorylation level was down-regulated.
Conclusions:
Our results show that morusin could inhibit the growth of RCC cells in vitro and in vivo through MAPK signal pathways. Thus, morusin could be a potential anti-cancer agent for RCC.
Insights
Morusin effectively inhibits renal cell carcinoma (RCC) growth and migration by inducing apoptosis and cell cycle arrest. This natural compound shows potential as an anti-cancer agent for RCC, impacting MAPK signaling pathways.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Renal cell carcinoma (RCC) is a significant kidney malignancy requiring novel therapeutic strategies.
- Morusin, a prenylated flavonoid, exhibits known anticancer properties by inhibiting cancer cell proliferation and tumorigenesis.
Purpose of the Study:
- To investigate the efficacy of morusin as a potential therapeutic agent against renal cell carcinoma (RCC).
- To elucidate the mechanisms underlying morusin's anti-cancer effects in RCC cells and in vivo.
Main Methods:
- Cell proliferation, migration, apoptosis, and cell cycle were assessed using CCK-8, transwell assays, Annexin V/7-AAD staining, and flow cytometry, respectively.
- Quantitative real-time PCR and Western blotting were employed to analyze target gene expression at mRNA and protein levels.
- In vivo efficacy was evaluated using a nude mouse xenograft model.
Main Results:
- Morusin significantly inhibited the growth and migration of three RCC cell lines (769-P, 786-O, OSRC-2).
- Morusin induced apoptosis, caused cell cycle arrest in the G1 phase, and suppressed RCC tumorigenesis in vivo.
- Morusin modulated the mitogen-activated protein kinase (MAPK) pathway, up-regulating p-p38 and p-JNK while down-regulating ERK phosphorylation.
Conclusions:
- Morusin demonstrates potent anti-cancer activity against renal cell carcinoma (RCC) both in vitro and in vivo.
- The observed anti-cancer effects are mediated through the modulation of MAPK signaling pathways.
- Morusin represents a promising candidate for the development of novel therapeutic agents for RCC.
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