PMID- 22745580
OWN - NLM
STAT- MEDLINE
DCOM- 20121025
LR  - 20211021
IS  - 1449-2288 (Electronic)
IS  - 1449-2288 (Linking)
VI  - 8
IP  - 6
DP  - 2012
TI  - Oridonin up-regulates expression of P21 and induces autophagy and apoptosis in 
      human prostate cancer cells.
PG  - 901-12
LID - 10.7150/ijbs.4554 [doi]
AB  - BACKGROUND: Oridonin (ORI) could inhibit the proliferation and induce apoptosis 
      in various cancer cell lines. However, the mechanism is not fully understood. 
      METHODS: Human prostate cancer (HPC) cells were cultured in vitro and cell 
      viability was detected by the CCK-8 assay. The ultrastructure changes were 
      observed under transmission electron microscope (TEM). Chemical staining with 
      acridine orange (AO), MDC or DAPI was used to detect acidic vesicular organelles 
      (AVOs) and alternation of DNA. Expression of LC3 and P21 was detected by Western 
      Blot. Apoptotic rates and cell cycle arrest were detected by FACS. RESULTS: Our 
      study demonstrated that after ORI treatment, the proliferations of human prostate 
      cancer (HPC) cell lines PC-3 and LNCaP were inhibited in a concentration and 
      time-dependent manner. ORI induced cell cycle arrest at the G2/M phase. A large 
      number of autophagosomes with double-membrane structure and acidic vesicular 
      organelles (AVOs) were detected in the cytoplasm of HPC cells treated with ORI 
      for 24 hours. ORI resulted in the conversion of LC3-I to LC3-II and recruitment 
      of LC3-II to the autophagosomal membranes. Autophagy inhibitor 3-methyladenine 
      (3-MA) reduced AVOs formation and inhibited LC3-I to LC3-II conversion. At 48 h, 
      DNA fragmentation, chromatin condensation and disappearance of surface microvilli 
      were detected in ORI-treated cells. ORI induced a significant increase in the 
      number of apoptotic cells (PC-3: 5.4% to 27.0%, LNCaP: 5.3% to 31.0%). Promoting 
      autophagy by nutrient starvation increased cell viability, while inhibition of 
      autophagy by 3-MA promoted cell death. The expression of P21 was increased by 
      ORI, which could be completely reversed by the inhibition of autophagy. 
      CONCLUSIONS: Our findings indicated that autophagy occurred before the onset of 
      apoptosis and protected cancer cells in ORI-treated HPC cells. P21 was involved 
      in ORI-induced autophagy and apoptosis. Our results provide an experimental basis 
      for understand the anti-tumor mechanism of ORI as treatment for prostate cancer.
FAU - Li, Xiang
AU  - Li X
AD  - Institute of Cell Biology, Zhejiang University, Hangzhou 310058, China.
FAU - Li, Xiang
AU  - Li X
FAU - Wang, Jiaxiong
AU  - Wang J
FAU - Ye, Zaiyuan
AU  - Ye Z
FAU - Li, Ji-Cheng
AU  - Li JC
LA  - eng
PT  - Journal Article
DEP - 20120622
PL  - Australia
TA  - Int J Biol Sci
JT  - International journal of biological sciences
JID - 101235568
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Diterpenes, Kaurane)
RN  - 0 (MAP1LC3A protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0APJ98UCLQ (oridonin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cyclin-Dependent Kinase Inhibitor p21/*metabolism
MH  - Diterpenes, Kaurane/*pharmacology
MH  - Humans
MH  - Male
MH  - Microtubule-Associated Proteins/metabolism
MH  - Prostatic Neoplasms/*metabolism
PMC - PMC3385012
OTO - NOTNLM
OT  - P21.
OT  - apoptosis
OT  - autophagy
OT  - oridonin
OT  - prostate cancer
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2012/06/30 06:00
MHDA- 2012/10/26 06:00
PMCR- 2012/01/01
CRDT- 2012/06/30 06:00
PHST- 2012/05/10 00:00 [received]
PHST- 2012/06/11 00:00 [accepted]
PHST- 2012/06/30 06:00 [entrez]
PHST- 2012/06/30 06:00 [pubmed]
PHST- 2012/10/26 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - ijbsv08p0901 [pii]
AID - 10.7150/ijbs.4554 [doi]
PST - ppublish
SO  - Int J Biol Sci. 2012;8(6):901-12. doi: 10.7150/ijbs.4554. Epub 2012 Jun 22.