Oleanolic acid arrests cell cycle and induces apoptosis via ROS-mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells.
Summary of "Oleanolic acid arrests cell cycle and induces apoptosis via ROS-mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells."
Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits potential anti-tumor activity against many tumor cell lines. This study aims to examine the anti-tumor activity of OA on pancreatic cancer cells and its potential molecular mechanism. The results showed that the proliferation of Panc-28 cells was inhibited by OA in a concentration-dependent manner, with an IC(50) (The half maximal inhibitory concentration) value of 46.35 µg ml(-1) , as determined by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The cell cycle was arrested in S phase and G2/M phase by OA. The study also showed that OA could induce remarkable apoptosis, evidenced by an increased percentage of early/late apoptotic cells, DNA ladder and nuclear morphology change. Further study revealed that OA could induce Reactive Oxygen Species (ROS) generation, mitochondrial depolarization, release of cytochrome C, lysosomal membrane permeabilization and leakage of cathepin B. The expression of apoptosis-correlated proteins was also affected in cells treated with OA, including activation of caspases-3/9 and cleavage of PARP. Further study confirmed that ROS scavenger vitamin C could reverse the apoptosis induced by OA in Panc-28 cells. Our results provide evidence that OA arrests the cell cycle and induces apoptosis, possibly via ROS-mediated mitochondrial and a lysosomal pathway in Panc-28 cells. Copyright © 2012 John Wiley & Sons, Ltd.
Affiliation
Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China; Graduate University, Chinese Academy of Sciences, Beijing, 100049, China.
Journal Details
This article was published in the following journal.
Name: Journal of applied toxicology : JAT
ISSN: 1099-1263
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22678527
- DOI: http://dx.doi.org/10.1002/jat.2725
Medical and Biotech [MESH] Definitions
Teniposide
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle.
Pentostatin
A potent inhibitor of ADENOSINE DEAMINASE. The drug induces APOPTOSIS of LYMPHOCYTES, and is used in the treatment of many lymphoproliferative malignancies, particularly HAIRY CELL LEUKEMIA. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity.
Oleanolic Acid
A pentacyclic triterpene that occurs widely in many PLANTS as the free acid or the aglycone for many SAPONINS. It is biosynthesized from lupane. It can rearrange to the isomer, ursolic acid, or be oxidized to taraxasterol and amyrin.
Glycyrrhetinic Acid
An oleanolic acid from GLYCYRRHIZA that has some antiallergic, antibacterial, and antiviral properties. It is used topically for allergic or infectious skin inflammation and orally for its aldosterone effects in electrolyte regulation.
Etoposide
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
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