PMID- 21642840
OWN - NLM
STAT- MEDLINE
DCOM- 20111205
LR  - 20211203
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 22
IP  - 8
DP  - 2011 Sep
TI  - Triterpenoid pristimerin synergizes with taxol to induce cervical cancer cell 
      death through reactive oxygen species-mediated mitochondrial dysfunction.
PG  - 763-73
LID - 10.1097/CAD.0b013e328347181a [doi]
AB  - A combined treatment with conventional chemotherapies can enhance the 
      effectiveness of chemotherapeutic agents against cancers. Here, we have shown 
      that the naturally occurring triterpenoids synergistically enhance the response 
      of cervical cancer cells to taxol. Of the triterpenoid compounds, pristimerin 
      enhanced the anticancer effect of taxol with the highest efficiency by 
      combination. Pristimerin synergizes with taxol to inhibit clonogenic survival and 
      tumor growth in nude mice, and to enhance cell death in cervical cancer cells. A 
      combined treatment with taxol and pristimerin induced cervical cancer cell death 
      by increasing intracellular reactive oxygen species levels, upregulation of death 
      receptor death receptor 5 (DR5), activation of Bax, and dissipation of 
      mitochondrial membrane potential. Treatment with N-acetyl-L-cysteine, a 
      thiol-containing antioxidant completely blocked combined treatment-induced Bax 
      translocation as well as DR5 upregulation. Moreover, inhibition of Jun N-terminal 
      kinase/c-Jun pathway attenuated cell death by blocking DR5 upregulation and Bax 
      activation. These results indicate that the triterpenoid, pristimerin, 
      synergistically enhances taxol response of cervical cancer cells through DR5 
      expression and Bax activation. Furthermore, the reactive oxygen species-dependent 
      activation of the Jun N-terminal kinase/c-Jun pathway is required for the DR5 
      upregulation and Bax activation. The molecular mechanism revealed by this study 
      may aid in the design of future combination cancer therapies against cells with 
      intrinsically reduced sensitivity to taxol.
FAU - Eum, Da-Young
AU  - Eum DY
AD  - Department of Chemistry, College of Medicine, Hanyang University, Seoul, Korea.
FAU - Byun, Joo-Yun
AU  - Byun JY
FAU - Yoon, Chang-Hwan
AU  - Yoon CH
FAU - Seo, Woo-Duck
AU  - Seo WD
FAU - Park, Ki-Hun
AU  - Park KH
FAU - Lee, Jin-Hwan
AU  - Lee JH
FAU - Chung, Hee Young
AU  - Chung HY
FAU - An, Sungkwan
AU  - An S
FAU - Suh, Yongjoon
AU  - Suh Y
FAU - Kim, Min-Jung
AU  - Kim MJ
FAU - Lee, Su-Jae
AU  - Lee SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Pentacyclic Triterpenes)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Triterpenes)
RN  - 0 (bcl-2-Associated X Protein)
RN  - L8GG98663L (celastrol)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Animals
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Cell Death/drug effects
MH  - Drug Synergism
MH  - Female
MH  - HeLa Cells
MH  - Humans
MH  - Membrane Potential, Mitochondrial/*drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Paclitaxel/administration & dosage
MH  - Pentacyclic Triterpenes
MH  - Reactive Oxygen Species/*metabolism
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics
MH  - Triterpenes/administration & dosage
MH  - Up-Regulation/drug effects
MH  - Uterine Cervical Neoplasms/*drug therapy/pathology
MH  - Xenograft Model Antitumor Assays
MH  - bcl-2-Associated X Protein/metabolism
EDAT- 2011/06/07 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/06/07 06:00
PHST- 2011/06/07 06:00 [entrez]
PHST- 2011/06/07 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 10.1097/CAD.0b013e328347181a [doi]
PST - ppublish
SO  - Anticancer Drugs. 2011 Sep;22(8):763-73. doi: 10.1097/CAD.0b013e328347181a.