Wogonin combined with cinnamaldehyde synergistically induces ferroptosis by increasing PTGS2 in breast cancer.

Wogonin and cinnamaldehyde, extracted from the traditional Chinese herbs Scutellaria baicalensis Georgi and Cinnamomum cassia Presl, respectively, have extensive pharmacological effects. They are individually effective against breast cancer but require much higher doses than the current drugs. However, it is currently unclear whether these two natural medicines can work synergistically at low doses to achieve the effect of treating breast cancer. In this study, in vitro experiments investigate the synergistic effects of wogonin and cinnamaldehyde on suppressing breast cancer cell proliferation. Network pharmacology and bioinformatics approaches are utilized to determine the potential mechanisms and key targets underlying the therapeutic effects of wogonin and cinnamaldehyde in breast cancer, which are subsequently verified. Furthermore, animal experiments are conducted to confirm the in vivo anti-tumor effectiveness and safety of wogonin and cinnamaldehyde. The results show that wogonin and cinnamaldehyde demonstrate synergistic effects in suppressing breast cancer cell proliferation. Network pharmacology indicates that the anti-breast cancer mechanisms of wogonin and cinnamaldehyde are related to the response to oxygen-containing compounds. Bioinformatics analysis further identifies PTGS2 as a crucial target for the anti-breast cancer effects of these two natural compounds. Mechanistically, wogonin and cinnamaldehyde can synergistically promote the expression of PTGS2, thereby inducing ferroptosis in breast cancer cells. Then, in vivo validation experiments show that these two natural compounds exhibit excellent biosafety. In conclusion, wogonin and cinnamaldehyde may work synergistically to enhance PTGS2 expression at minimal doses and trigger ferroptosis in breast cancer cells, thus suppressing breast cancer progression.