Keywords
How to Cite
Abstract
Doxorubicin (DOX) is one of the most widely used anticancer drugs, but cumulative heart damage, bone marrow suppression and efflux-pump-mediated resistance limit how much of it patients can receive. β-Caryophyllene (BCP) is a bicyclic sesquiterpene found in the essential oils of several hundred plant species. It is a selective agonist of the cannabinoid type 2 (CB2) receptor, has low toxicity in rodents and is used as a food flavouring. This review brings together the evidence for using BCP alongside DOX. First, it outlines how DOX works and why it damages healthy tissue. It then summarises the sources, pharmacology and safety of BCP and its direct anticancer effects. Cell studies show that BCP and its oxide (β-caryophyllene oxide, BCPO) can increase DOX cytotoxicity in leukaemia, colon and liver cancer cells, mainly by limiting P-glycoprotein-mediated efflux. The effect is not universal, however: it was absent in at least one fully resistant cell line. Evidence that BCP protects the heart during DOX treatment is suggestive but still indirect in the sources reviewed here. Both drugs face delivery problems. DOX already has clinical liposomal forms, while BCP's poor solubility and volatility have been addressed with self-emulsifying drug delivery systems (SEDDS), which raised its peak plasma level 3.6-fold in healthy volunteers. Carrying both agents in one lipid system is an attractive idea, but it has not yet been tested in animals. We close by listing the experiments needed before the combination can move forward: checkerboard synergy studies, matched normal-cell controls, pharmacokinetic studies and in vivo cardiac safety testing.