Dentatin from Clausena excavata Induces Apoptosis in HepG2 Cells via Mitochondrial Mediated Signaling
| Autor: | Ahmad Bustamam Abdul, Ismail Adam Arbab, Theebaa Anasamy, Nozlena Abdul Samad, Heshu Sulaiman Rahman, Siddig Ibrahim Abdelwahab, Mohd Aspollah Sukari, A. Reenaa Joys Andas |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Cell cycle checkpoint Epidemiology bcl-X Protein Apoptosis Mitochondria Liver Clausena excavata Plant Roots Inhibitory Concentration 50 medicine Humans Caspase Cell Proliferation bcl-2-Associated X Protein biology Caspase 3 Plant Extracts Cytochrome c Clausena Public Health Environmental and Occupational Health NF-kappa B Cytochromes c Hep G2 Cells biology.organism_classification medicine.disease Molecular biology G1 Phase Cell Cycle Checkpoints Caspase 9 Blot Oncology Hepatocellular carcinoma biology.protein Cancer research Apoptotic signaling pathway Heterocyclic Compounds 3-Ring Signal Transduction |
| Zdroj: | Asian Pacific journal of cancer prevention : APJCP. 16(10) |
| ISSN: | 2476-762X |
| Popis: | Hepatocellular carcinoma (HCC) is a primary liver cancer with high global incidence and mortality rates. Current candidate drugs to treat HCC remain lacking and those in use possess undesirable side effects. In this investigation, the antiproliferative effects of dentatin (DTN), a natural coumarin, were evaluated on HepG2 cells and DTN's probable preliminary molecular mechanisms in apoptosis induction were further investigated. DTN significantly (p0.05) suppressed proliferation of HepG2 cells with an IC50 value of 12.0 μg/mL, without affecting human normal liver cells, WRL-68 (IC5050 μg/mL) causing G0/G1 cell cycle arrest via apoptosis induction. Caspase colorimetric assays showed markedly increased levels of caspase-3 and caspase-9 activities throughout the treatment period. Western blotting of treated HepG2 cells revealed inhibition of NF-κB that triggers the mitochondrial-mediated apoptotic signaling pathway by up-regulating cytoplasmic cytochrome c and Bax, and down-regulating Bcl-2 and Bcl-xL. The current findings suggest DTN has the potential to be developed further as an anticancer compound targeting human HCC. |
| Databáze: | OpenAIRE |
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