Icariside II suppresses bladder cancer progression via endoplasmic reticulum stress-mediated autophagy and lysosomal dysfunction.

BACKGROUND

Icariside II is an active compound extracted from Herba Epimedii, a traditional Chinese medicine known for its remarkable effects in treating erectile dysfunction and arthritis. However, the specific mechanism underlying its anticancer activity in bladder cancer remains unclear. This study aims to explore the effects and mechanisms of Icariside II in bladder cancer.

METHODS

We validated the role of Icariside II in bladder cancer through various in vitro experiments. Additionally, transcriptome sequencing was performed to explore the potential mechanism of Icariside II in suppressing bladder cancer. The results of the transcriptome sequencing were further confirmed by Western Blot, immunofluorescence, and Transmission Electron Microscope. In vivo validation was conducted using tumor xenograft models.

RESULTS

Our findings demonstrated that Icariside II effectively inhibited the proliferation and migration of bladder cancer. Transcriptome sequencing revealed significant alterations in autophagy and Endoplasmic Reticulum stress related genes in bladder cancer cells after treatment with Icariside II. This result was supported by the observations made through Transmission Electron Microscope and Western Blot. Further investigations indicated that Icariside II induced autophagy through the IRE1α and PERK pathway and inhibited autophagic flow by reducing the number of lysosomes and suppressing their activity. In tumor xenograft models, Icariside II significantly inhibited bladder cancer proliferation.

CONCLUSIONS

Our data suggest that Icariside II holds promise as a natural medicine for the significant inhibition of bladder cancer, achieved through the induction of endoplasmic reticulum stress-induced autophagy and inhibition of lysosomal activity.