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Dandelion root extracts and taraxasterol inhibit LPS‑induced colorectal cancer cell viability by blocking
Kerry Yang1, Yuehong Wang2,3
1Faculty of Health Sciences, McMaster University, Hamilton, Ontario L8S 4L8, Canada.
Abstract:
Colorectal cancer is the fourth leading cause of cancer-related death worldwide. Notably, abnormalities in intestinal bacteria may contribute to the initiation or progression of colorectal cancer. Lipopolysaccharide (LPS), a bacterial endotoxin, is elevated in patients with colorectal cancer. The present study investigated the protective effects of dandelion root extracts and taraxasterol (TS; a major pharmacologically active compound in dandelion root extracts) on LPS-induced colorectal cancer cell viability, as well as the underlying mechanisms. Cell viability was assessed by MTT assay, and protein and gene expression levels were determined by western blotting and quantitative PCR. It was revealed that LPS at a low dose (0.5 µg/ml) significantly promoted the viability of human colorectal cancer cells but did not affect normal colon epithelial cells. The addition of dandelion root extracts (0.1-1 mg/ml) or TS (0.05-1 µg/ml) was able to reverse the LPS-induced increase in colorectal cancer cell viability and colony formation. Mechanistically, dandelion root extracts or TS may inhibit the LPS-promoted toll-like receptor 4 (TLR4)/NFκB-p65 pathway and transcription levels of pro-inflammatory genes (TNFα, IL4 and IL6). Compared with normal colon epithelial cells, human colorectal cancer cells had higher expression levels of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), which could be further enhanced by LPS treatment but this was reversed by co-incubation with dandelion root extracts or TS. In addition, suppression of the TLR4/NFκB-p65 pathway with CLI095 significantly reversed the stimulatory effect of LPS on the expression levels of ACE2 and TMPRSS2, whereas TNFα (10 ng/ml) markedly induced the expression levels of ACE2 and TMPRSS2. In conclusion, the present study suggested that dandelion root extracts and TS could be used as prevention strategies for reversing bacteria-driven colorectal cancer cell viability.
Insights
Dandelion root extracts and taraxasterol (TS) show protective effects against colorectal cancer. These compounds reverse lipopolysaccharide (LPS)-induced cell viability by inhibiting key inflammatory pathways.
Area of Science:
- Gastroenterology
- Oncology
- Microbiology
Background:
- Colorectal cancer (CRC) is a leading cause of cancer death globally.
- Intestinal bacteria and their products, like lipopolysaccharide (LPS), are implicated in CRC development.
- Elevated LPS levels are observed in CRC patients, suggesting a role for bacterial endotoxins.
Purpose of the Study:
- To investigate the protective effects of dandelion root extracts and taraxasterol (TS) on LPS-induced CRC cell viability.
- To elucidate the underlying molecular mechanisms of action for dandelion extracts and TS.
- To explore the role of TLR4/NFκB-p65 and ACE2/TMPRSS2 pathways in LPS-mediated CRC cell proliferation.
Main Methods:
- Cell viability was assessed using MTT assays.
- Protein and gene expression levels were determined via western blotting and quantitative PCR.
- Specific pathway inhibitors (CLI095) and inflammatory cytokines (TNFα) were used to probe molecular mechanisms.
Main Results:
- LPS (0.5 µg/ml) significantly promoted human colorectal cancer cell viability.
- Dandelion root extracts (0.1-1 mg/ml) and TS (0.05-1 µg/ml) reversed LPS-induced increases in cell viability and colony formation.
- Dandelion extracts/TS inhibited the LPS-promoted TLR4/NFκB-p65 pathway and pro-inflammatory gene expression, while reversing LPS-induced ACE2 and TMPRSS2 upregulation.
Conclusions:
- Dandelion root extracts and TS demonstrate potential as preventative agents against bacteria-driven colorectal cancer.
- These natural compounds may exert their effects by modulating the TLR4/NFκB-p65 signaling pathway and influencing ACE2/TMPRSS2 expression.
- The findings suggest a therapeutic strategy involving dandelion-derived compounds for colorectal cancer prevention.
