The natural product Oleuropein shows enhanced anticancer and cardioprotective activity when co-administered in vivo with Doxorubicin

Oleuropein (OLEU) is a phenolic compound widely consumed as part of the Mediterranean diet and found in large amounts in olive fruit and leaves of Olea europaea L. OLEU has pleiotropic pharmacological properties, such as antioxidant, anti-inflammatory, anti-atherogenic and anti-cancer. Doxorubicin (DXR) is an anthracycline broadly used as chemotherapeutic for the treatment of solid tumors, although it presents significant side effects. We investigated the in vivo anticancer and cardioprotective effect of OLEU when given together with DXR in mice with melanoma and colon cancer. We designed chronic cardiotoxicity models [1] in C57/BL6 and Balb/c mice that were injected (day-0) subcutaneously with syngeneic B16.F1 (10⁵/mouse) and CT-26 (10⁶/mouse) cells, respectively. When tumors were palpable (day-11 post-inoculation), we administered intraperitoneally OLEU and/or DXR (total 2100 mg/Kg and 18 mg/Kg, respectively; divided in 6 doses given every other day) and monitored tumor growth (tumor dimensions measured by a caliper) and cardiotoxicity (with echosonography performed before cancer cell inoculation and prior sacrifice) for 23 days. The concomitant administration of OLEU and DXR significantly retarded tumor growth, particularly of melanoma. Additionally, the DXR-induced chronic cardiotoxicity was reduced (ΔFS ~4%) in mice treated with the OLEU/DXR combination compared to animals treated only with DXR (ΔFS ~10%). Further experiments concerning the impact of this co-treatment protocol are needed to acquire more holistic and solid conclusions.

• References

• 1 Andreadou I, Mikros E, Ioannidis K, Sigala Fr, Naka K, Kostidis S. etal. Oleuropein prevents doxorubicin-induced cardiomyopathy interfering with signaling molecules and cardiomyocyte metabolism, J Mol and Cell Cardiol 2014; 69: 4-16