Inonotsutriol E from Inonotus obliquus exhibits promising anti breast cancer activity via regulating the JAK2/STAT3 signaling pathway

The aim of the present study was to investigate the small molecule anticancer agents in the medicinal fungus Inonotus obliquus and further characterize their possible molecular mechanisms. Chemical fractionation of the ethanol extract of this fungus yielded a panel of lanostane triterpenoids (1–13) and their structures were characterized on the basis of spectroscopic methods. Subsequent preliminary biological screening on these triterpenoids revealed significant cytotoxicity against various tumor cell lines, and inonotsutriol E (ITE, 1) showed the best activity. Of note, ITE displayed stronger inhibitory effect on breast cancer (BC) than other tumor cell lines. Functional assays revealed that ITE significantly inhibited the growth and migration of BC cells and exerted promising antitumor activity in patient-derived organoids (PDO). Further mechanistic study demonstrated that the anti-BC activity of ITE was achieved via inhibiting JAK2/STAT3 signal axis. Taken together, the current work has demonstrated the therapeutic material basis of I. obliquus and provided further evidence for the traditional application of this medicinal species in cancer prevention and treatment.