Exploring the Mechanism of Cytotoxic Activity of β-Caryophyllene Oxide and its Potential to Enhance the Activity of Doxorubicin

Plant-derived compounds, including flavonoids, sesquiterpenes, and others, have been widely investigated for their role in cancer treatment. Here, we highlight the significance of some natural compounds (β-caryophyllene oxide) in enhancing doxorubicin's chemotherapeutic cytotoxicity. We also determined a novel mechanism of cytotoxicity for β-caryophyllene oxide by revealing its ability to bind with the DNA. This potentially causes its cytotoxicity when added alone and its ability to enhance doxorubicin's cytotoxicity. We also show that some natural compounds (epicatechin) may provide protection to cancer cells against doxorubicin's toxicity. This is most likely caused by their antioxidant behavior which potentially suppressed the doxorubicin-induced reactive oxygen species (ROS) resulting in a decrease in its cytotoxicity. Moreover, similar suppression in the cytotoxicity of β-caryophyllene oxide was noticed when incubated with the other flavonoids.