Chemotherapeutic activity of Silymarin combined with doxorubicin liposomes in 4T1 breast cancer cells

Cancer is the second leading cause of death worldwide. Despite great efforts over many years, today cancer treatment is not very effective. The main reasons for cancer chemotherapy failure are high cytotoxicity, low response rates in solid tumors, and development of resistance. Different experimental studies have shown that drug combination using low toxicity natural compounds such as polyphenols can reduce the required dose of cytotoxic drugs for cancer treatment. The polyphenolic compound, Silymarin (SLM), is an active extract from the seeds of the plant milk thistle (Silybum Marianum). It is well known for its hepatoprotective, antioxidant and chemoprotective effects. In the present study, we investigated whether the combination of Silymarin with Caelyx° (commercial doxorubicin liposome (DXL)) could enhance the cytotoxicity on 4T1 breast cancer cells in vitro. For this, 4T1 breast cancer cells were exposed to Silymarin, DXL and their combination at different molar ratios, to elucidate if the two drugs could dictate synergistic effect in vitro. Results indicated that SLM-DXL combination at 100 and 300 molar ratios, exert synergistic growth-inhibitory effects. These synergistic effects were observed only at lower SLM-DXL concentrations. In conclusion, it is conceivable that in SLMDXL combination chemotherapy, drug ratios play a key role which determine the final response following treatment. Thus, using liposomes as targeted drug delivery systems, it would be possible to achieve appropriate combination of the two drugs at correct doses and correct administration intervals clinically