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Walnut Phenolic Extract and Its Bioactive Compounds Suppress Colon Cancer Cell Growth by Regulating Colon Cancer
Jisoo Lee1, Yoo-Sun Kim2, JaeHwan Lee3
1Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea. dlwltn233@naver.com.
Abstract:
Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133⁺CD44⁺ cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE. As a result, survival of the CD133⁺CD44⁺ HCT116 cells was inhibited and cell differentiation was induced by WPE. In addition, WPE down-regulated the CSC markers, CD133, CD44, DLK1, and Notch1, as well as the β-catenin/p-GSK3β signaling pathway. WPE suppressed the self-renewal capacity of CSCs. Furthermore, the WPE exhibited stronger anti-CSC effects than its individual bioactive compounds. Finally, the WPE inhibited specific CSC markers in primary colon cancer cells isolated from primary colon tumor. These results suggest that WPE can suppress colon cancer by regulating the characteristics of colon CSCs.
Insights
Walnut phenolic extract (WPE) effectively targets colon cancer stem cells (CSCs), inhibiting their survival and self-renewal. WPE demonstrates potent anti-CSC activity, surpassing individual compounds and offering a promising natural approach for colon cancer therapy.
Area of Science:
- Nutritional biochemistry
- Cancer biology
- Pharmacology
Background:
- Walnuts possess known health benefits, including antioxidant and cardiovascular protective properties.
- Cancer stem cells (CSCs) are implicated in chemotherapy resistance and tumor recurrence.
- Limited research exists on the anti-CSC effects of walnut components.
Purpose of the Study:
- To investigate the anti-cancer stem cell (CSC) potential of walnut phenolic extract (WPE).
- To evaluate the effects of WPE and its bioactive compounds on colon CSCs.
- To elucidate the molecular mechanisms underlying WPE's anti-CSC activity.
Main Methods:
- Isolation of CD133+CD44+ colon CSCs from HCT116 cells using fluorescence-activated cell sorting (FACS).
- Treatment of isolated CSCs with WPE and its individual bioactive compounds ((+)-catechin, chlorogenic acid, ellagic acid, gallic acid).
- Assessment of CSC marker expression (CD133, CD44, DLK1, Notch1) and signaling pathways (β-catenin/p-GSK3β).
- Evaluation of WPE's effect on CSC self-renewal capacity and primary colon cancer cells.
Main Results:
- WPE significantly inhibited the survival of CD133+CD44+ HCT116 cells and induced cell differentiation.
- WPE downregulated key CSC markers (CD133, CD44, DLK1, Notch1) and the β-catenin/p-GSK3β signaling pathway.
- WPE demonstrated superior anti-CSC effects compared to its individual bioactive compounds.
- WPE suppressed the self-renewal capacity of colon CSCs and inhibited CSC markers in primary colon cancer cells.
Conclusions:
- Walnut phenolic extract (WPE) exhibits significant potential in suppressing colon cancer by targeting cancer stem cells.
- WPE effectively regulates colon CSC characteristics, including survival, differentiation, and self-renewal.
- The findings suggest WPE as a promising natural therapeutic agent for colon cancer, warranting further investigation.
