Abstract
Melanoma is a malignancy with a high mortality rate. STAT3, a transcription factor
that plays an important role in melanoma development, is a well-established target for treating melanoma. Ranunculi Ternati Radix (RTR), the dried root of Ranunculus ternatus Thunb., is commonly prescribed to treat cancer in China. However, pharmacological effects of RTR on melanoma, and mechanisms of its actions are unclear. Some constituents of RTR, such as ursolic acid, oleanolic acid, and betulinic acid have anti-melanoma effects, and have been shown to inhibit STAT3 signaling. In this study, we investigated the anti-melanoma effects of RTR and explored the involvement of STAT3 signaling in the effects.
We found that the ethyl acetate fraction of the 70% ethanol extract of RTR (EA-RTR) dose-dependently reduces cell viabilities in A375 and A2058 human melanoma cells and inhibits tumor growth in a B16 melanoma allograft mouse model without obvious toxicity. Mechanistic studies showed that EA-RTR lowers mRNA levels of STAT3 and STAT3-targeted genes MCL-1 and BCL-XL in melanoma cells. Overexpression of STAT3 in melanoma cells significantly diminishes the effects of EA-RTR in reducing cell viability, suggesting the contribution of inhibiting STAT3 in the anti-melanoma effects of EA-RTR. To further understand the mechanisms of inhibiting STAT3 by EA-RTR, we performed microRNA array analysis and found that the levels of miR-125 family members, miR-125a, miR-125b and miR-351, are upregulated by EA-RTR in the B16 tumor tissues.
miR-125 family microRNAs have been reported to act as tumor suppressors by targeting STAT3.
Taken together, our data demonstrate that EA-RTR has anti-melanoma effects, and upregulating miR-125 family microRNAs and inhibiting STAT3 signaling are associated with the effects of EA-RTR. This study lays the groundwork for developing EA-RTR as an effective and safe modality for treating melanoma.
that plays an important role in melanoma development, is a well-established target for treating melanoma. Ranunculi Ternati Radix (RTR), the dried root of Ranunculus ternatus Thunb., is commonly prescribed to treat cancer in China. However, pharmacological effects of RTR on melanoma, and mechanisms of its actions are unclear. Some constituents of RTR, such as ursolic acid, oleanolic acid, and betulinic acid have anti-melanoma effects, and have been shown to inhibit STAT3 signaling. In this study, we investigated the anti-melanoma effects of RTR and explored the involvement of STAT3 signaling in the effects.
We found that the ethyl acetate fraction of the 70% ethanol extract of RTR (EA-RTR) dose-dependently reduces cell viabilities in A375 and A2058 human melanoma cells and inhibits tumor growth in a B16 melanoma allograft mouse model without obvious toxicity. Mechanistic studies showed that EA-RTR lowers mRNA levels of STAT3 and STAT3-targeted genes MCL-1 and BCL-XL in melanoma cells. Overexpression of STAT3 in melanoma cells significantly diminishes the effects of EA-RTR in reducing cell viability, suggesting the contribution of inhibiting STAT3 in the anti-melanoma effects of EA-RTR. To further understand the mechanisms of inhibiting STAT3 by EA-RTR, we performed microRNA array analysis and found that the levels of miR-125 family members, miR-125a, miR-125b and miR-351, are upregulated by EA-RTR in the B16 tumor tissues.
miR-125 family microRNAs have been reported to act as tumor suppressors by targeting STAT3.
Taken together, our data demonstrate that EA-RTR has anti-melanoma effects, and upregulating miR-125 family microRNAs and inhibiting STAT3 signaling are associated with the effects of EA-RTR. This study lays the groundwork for developing EA-RTR as an effective and safe modality for treating melanoma.
| Original language | English |
|---|---|
| Pages | 79 |
| Number of pages | 1 |
| Publication status | Published - 19 Nov 2022 |
| Event | 第七届可食和药用植物资源及功能成分国际学术研讨会 = 7th International Symposium on Edible & Medical Plant Resources and the Bioactive Ingredients, ISEPR 2022 - Urumqi, China Duration: 19 Nov 2022 → 19 Nov 2022 http://www.xjipc.cas.cn/tzggnew/202211/t20221116_6549481.html |
Symposium
| Symposium | 第七届可食和药用植物资源及功能成分国际学术研讨会 = 7th International Symposium on Edible & Medical Plant Resources and the Bioactive Ingredients, ISEPR 2022 |
|---|---|
| Country/Territory | China |
| City | Urumqi |
| Period | 19/11/22 → 19/11/22 |
| Internet address |
User-Defined Keywords
- Ranunculi Ternati Radix
- STAT3
- miR-125
- miR-351
- Melanoma