Reviewed by Sophia Coveney

In a recent study published in Scientific Reports, researchers evaluated the anti-metastatic and anti-proliferative properties of all-trans retinoic acid (ATRA) and dandelion extract in breast cancer cells.

Study: Combined dandelion extract and all-trans retinoic acid induces cytotoxicity in human breast cancer cells. Image Credit: vetre/Shutterstock.com

Background

Breast cancer is one of the most common and deadly cancers worldwide. Age, diet, genetics, physical activity, sex hormones, obesity, and environmental carcinogens are implicated in breast cancer etiology.

Metastasis is the leading cause of death for breast cancer patients. Several drugs developed to treat breast cancer have adverse effects, including neurotoxicity, nephrotoxicity, and cardiac toxicity.

Natural health products have been increasingly explored as therapeutic agents for different diseases. They have fewer side effects and exert potent therapeutic effects. ATRA, a vitamin A derivative, is an anti-cancer agent that causes growth inhibition and induces apoptosis in numerous cancers.

Dandelion, a member of the Asteraceae family, has drawn immense attention in recent years. Dandelion organs contain flavonoids and L-chicoric acid that exhibit anti-cancer, anti-inflammatory, and antioxidant properties.

Dandelion has been used as a traditional medicine across Asia, North America, and Europe to improve disease outcomes, and studies have demonstrated the inhibitory and anti-metastatic effects of dandelion extract on cancer cells.

The study and findings

In the present study, researchers evaluated the effects of ATRA and dandelion extract on MDA-MB-231 and MCF-7 breast cancer cell lines. Cells were treated with different concentrations of ATRA, dandelion extract, or both and tested for viability. Dose-dependent inhibition of cell survival was observed 48 hours after treatments.

For further investigations, the team considered 40 μM ATRA for both cell lines and 1.5 mg/ml and 4 mg/ml dandelion extract for MCF-7 and MDA-MB-231 cells, respectively. Next, the gene expression of cells treated with ATRA, dandelion extract, or both at specified concentrations was evaluated.

The researchers noted significantly elevated matrix metalloproteinase 2 (MMP-2) expression in treated MCF-7 cells relative to untreated controls, with the highest expression with dandelion extract.

MMP-2 expression in MCF-7 cells co-treated with ATRA and dandelion extract was higher than in ATRA-treated cells. On the contrary, MMP-2 expression in MDA-MB-231 cells was significantly reduced in all treated groups relative to untreated controls, with no significant differences in expression among treatment groups.

By contrast, MMP-9 expression significantly declined in both cell lines across treatment groups relative to untreated controls.

MMP-9 expression was lower in co-treated MCF-7 cells relative to dandelion extract-treated cells. However, in MDA-MB-231 cells, MMP-9 expression did not significantly differ across treatment groups. All treated cells had lower interleukin (IL)-1β expression than controls. Nevertheless, this reduction in MCF-7 cells was much greater in dandelion and co-treatment groups than in ATRA-treated cells.

Likewise, IL-1β expression was significantly lower with co-treatment in MDA-MB-231 cells. Both cell lines exhibited significantly elevated p53 expression across treatment regimens compared to untreated cells. Co-treatment in both cell lines and dandelion extract treatment in MDA-MB-231 cells yielded significantly higher p53 expression than other treatments.

NM23 expression was significantly reduced in MCF-7 cells with all treatments and in MDA-MB-231 cells with ATRA and co-treatment relative to untreated cells. By contrast, dandelion extract treatment in MDA-MB-231 cells caused a significant increase in NM23 expression.

In MCF-7 cells, the dandelion and co-treatment groups had significantly lower NM23 levels than the ATRA group. All treated cells showed significantly increased Kangai 1 (KAI1) expression relative to untreated cells, which was significantly increased in dandelion extract-treated MCF-7 cells and ATRA-treated MDA-MB-231 cells.

Conclusions

To summarize, co-treatment with ATRA and dandelion extract was cytotoxic to both cancer cell lines, which resulted in p53 overexpression. In addition, IL-1β expression was reduced with all treatments in both cell lines. Dandelion extract and co-treatment decreased the expression of MMP-2 in MDA-MB-231 cells but increased it in MCF-7 cells while reducing MMP-9 expression in both cell lines.

Further, KAI1 expression increased in both cell lines with all treatments. However, NM23 expression increased with dandelion extract only in MDA-MB-231 cells, whereas other treatments reduced its expression.

Overall, the study demonstrated the potential impact of dandelion extract alone and with ATRA on the expression of genes involved in breast cancer cell proliferation and invasion.

Journal reference:

  • Rezaie H, Alipanah-Moghadam R, Jeddi F, et al. (2023). Combined dandelion extract and all-trans retinoic acid induces cytotoxicity in human breast cancer cells. Sci Rep. doi:10.1038/s41598-023-42177-z. https://www.nature.com/articles/s41598-023-42177-z