title: Upregulation of death receptor 5 and activation of caspase 8/3 play a critical role in ergosterol peroxide induced apoptosis in DU 145 prostate cancer cells.
abstract: BACKGROUND
  Though ergosterol peroxide (EP) derived from Neungyi mushrooms (Sarcodon aspratus) was known to have cytotoxic, apoptotic, anti-inflammatory and antimycobacterial effects, the underlying molecular mechanism of EP still remains unclear. Thus, in the present study, the apoptotic mechanism of EP was elucidated in DU 145 prostate cancer cells.
  
  
  METHODS
  Cell viability of prostate cancer cells was measured by MTT assay. To see whether EP induces the apoptosis, FACS, western blot and TUNEL assay were performed. To determine the role of Death receptor (DR) 5 molecules in EP-induced apoptosis in DU 145 prostate cancer cells, the silencing of DR 5 was performed by using siRNAs.
  
  
  RESULTS
  EP showed significant cytotoxicity against DU 145, PC 3, M2182 prostate cancer cells. Also, EP effectively increased the sub G1 population and terminal deoxynucleotidyl transferase DUTP nick end labeling (TUNEL) positive cells in DU 145 prostate cancer cells. Furthermore, western blotting revealed that EP cleaved poly (ADP-ribose) polymerase (PARP) and caspase 8/3, attenuated the expression of fluorescence loss in photobleaching (FLIP), Bcl-XL and Bcl-2 as well as activated Bax, Fas-associated death domain (FADD) and DR 5 in a concentration dependent manner in DU 145 prostate cancer cells. Conversely, caspase 8 inhibitor Z-IETD-FMK blocked the apoptotic ability of EP to cleave PARP and an increase of sub G1 population in DU 145 prostate cancer cells. Likewise, the silencing of DR 5 suppressed the cleavages of PARP induced by EP in DU 145 prostate cancer cells.
  
  
  CONCLUSIONS
  Overall, our findings suggest that ergosterol peroxide induces apoptosis via activation of death receptor 5 and caspase 8/3 in DU 145 prostate cancer cells as a cancer chemopreventive agent or dietary factor.
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Jonghyun
authors.initials: J
authors.lastname: Han
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Sohn
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Bonglee
authors.initials: B
authors.lastname: Kim
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Sunhee
authors.initials: S
authors.lastname: Kim
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Gunho
authors.initials: G
authors.lastname: Won
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Sangwook
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Moon Joon
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Hojin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Kyujin
authors.initials: K
authors.lastname: Chung
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Hoegidong, Dongdaemungu, Seoul, 130-701 Republic of Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
keywords: Apoptosis; Caspase 8/3; DR 5; DU 145 prostate cancer cells; Ergosterol peroxide; Z-IETD-FMK