Germacrone induces apoptosis as well as protective autophagy in human prostate cancer cells

Abstract

Background: Germacrone, a natural product isolated from the traditional Chinese medicine Rhizoma Curcuma, has been reported to exhibit antitumor activities in vitro. To further understand the antitumor mechanism of germacrone, we investigated the growth inhibitory effect of germacrone on the human prostate cancer cell lines PC-3 (androgen independent) and 22RV1 (androgen dependent). Materials and Methods: Prostate cancer cells were cultured with different concentrations of germacrone, and cell viability was measured by MTT assay. The levels of proteins were measured by Western blotting. Cell apoptosis was assessed by flow cytometry. Images of autophagy-related protein staining were captured by fluorescence microscopy. Autophagic flux was assessed by detecting the LC3B-II level. Results: Our results indicated that germacrone treatment significantly inhibited cell proliferation by inducing apoptosis in a dose-dependent manner, with IC50 values of 259 μM for PC-3 cells and 396.9 μM for 22RV1 cells. Germacrone-treated cells also exhibited induction of autophagy, as evidenced by elevated LC3B-II protein expression levels and punctuate patterns. Additionally, an autophagy inhibitor enhanced the growth inhibitory effect of germacrone. Moreover, the phosphorylationofAktandmTORwasinhibitedingermacrone-treated prostate cancer cells. Conclusion: Germacrone induced apoptosis and autophagy in prostate cancer cells by inhibiting the Akt/mTORsignaling pathway. Germacrone treatment also led to the activation of protective autophagy. These findings suggest that germacrone may potentially contribute to the development of a new therapeutic agent for prostate cancer treatment.