Abstract
Colorectal cancer (CRC) is one of the common tumors of the digestive system.
Fluorouracil (5-FU) is the sole first line drug for CRC. However, it has limitations
including severe toxicities. Huai-Hua-San (HHS), composed of two edible herbs
Sophorae Flos and Gardeniae Fructus, is one of the Chinese medicine formulas for
treating colorectal cancer. However, pharmacological basis of the formula’s application in treating CRC is lacking. In this study, our MTT assays showed that an extract of HHS (HHSE) dose-dependently reduced viability of HCT116, HCT8 and HT-29 CRC cells. Flow cytometry assays showed that HHSE induced apoptosis in these CRC cell lines in a dose-dependent manner. Importantly, HHSE dose-dependently restrained subcutaneous CT26 CRC growth in mice without overt toxicities. To understand the mechanisms of action of the extract, we performed network pharmacology analysis. KEGG pathway enrichment highlighted the involvement of PI3K/AKT signaling pathway in the anti-CRC effects of HHSE. Western blot analyses demonstrated that HHSE significantly lowered the protein levels of PI3K, AKT, phospho-AKT (Ser 473), indicating that inhibition of the PI3K/AKT pathway is associated with the anti-CRC effects of the extract. Our
findings provide pharmacological justifications for the use of HHS in treating CRC and suggest that HHSE can be developed into an effective and safe anti-CRC drug.
Fluorouracil (5-FU) is the sole first line drug for CRC. However, it has limitations
including severe toxicities. Huai-Hua-San (HHS), composed of two edible herbs
Sophorae Flos and Gardeniae Fructus, is one of the Chinese medicine formulas for
treating colorectal cancer. However, pharmacological basis of the formula’s application in treating CRC is lacking. In this study, our MTT assays showed that an extract of HHS (HHSE) dose-dependently reduced viability of HCT116, HCT8 and HT-29 CRC cells. Flow cytometry assays showed that HHSE induced apoptosis in these CRC cell lines in a dose-dependent manner. Importantly, HHSE dose-dependently restrained subcutaneous CT26 CRC growth in mice without overt toxicities. To understand the mechanisms of action of the extract, we performed network pharmacology analysis. KEGG pathway enrichment highlighted the involvement of PI3K/AKT signaling pathway in the anti-CRC effects of HHSE. Western blot analyses demonstrated that HHSE significantly lowered the protein levels of PI3K, AKT, phospho-AKT (Ser 473), indicating that inhibition of the PI3K/AKT pathway is associated with the anti-CRC effects of the extract. Our
findings provide pharmacological justifications for the use of HHS in treating CRC and suggest that HHSE can be developed into an effective and safe anti-CRC drug.
| Original language | English |
|---|---|
| Pages | 34 |
| 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
- Huai-Hua-San (HHS)
- Sophorae Flos
- Gardeniae Fructus
- Colorectal cancer (CRC)
- PI3K/AKT signaling pathway
