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p53 Cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo
- Source :
- Molecular carcinogenesis. 48(1)
- Publication Year :
- 2008
-
Abstract
- Berberine has been shown to have anti-carcinogenic effects. Since p53 is the most commonly mutated tumor suppressor gene, and a lack of functional p53 is associated with an increased risk of cancer development, we examined the effects of berberine on p53-positive and p53-deficient non-small cell human lung cancer cells in vitro and in vivo. Treatment of A549, which express wild-type p53, and H1299, which are p53-deficient, human lung cancer cells with berberine resulted in inhibition of cell proliferation and an increase in apoptotic cell death; however, A549 cells were more sensitive to the berberine-induced cytotoxic effects than H1299 cells. Further, the treatment of A549 cells with pifithrin-alpha, a specific inhibitor of p53, or transfection of A549 cells with a p53 antisense oligodeoxynucleotide resulted in a reduction in the berberine-induced inhibition of cell proliferation and apoptosis. The berberine-induced apoptosis of both the A549 and H1299 human lung cancer cells was associated with the disruption of mitochondrial membrane potential, reduction in the levels of Bcl-2, Bcl-xl while increase in Bax, Bak, and activation of caspase-3. Treatment of the cells with pan-caspase inhibitor (z-VAD-fmk) or caspase-3 inhibitor (z-DEVD-fmk) inhibited berberine-induced apoptosis, thus suggesting the role of caspase-3. Further, the administration of berberine by oral gavage inhibited the growth of s.c. A549 and H1299 lung tumor xenografts in athymic nude mice, however, the growth of tumor xenograft of H1299 cells was faster than A549 cells in mice and the chemotherapeutic effect of berberine was more pronounced in the p53-positive-A549 tumor xenograft than p53-deficient-H1299 tumor xenograft.
- Subjects :
- Cancer Research
Lung Neoplasms
Tumor suppressor gene
Berberine
Blotting, Western
Mice, Nude
Apoptosis
Bronchi
Enzyme-Linked Immunosorbent Assay
Biology
Pharmacology
chemistry.chemical_compound
Mice
Carcinoma, Non-Small-Cell Lung
Cytotoxic T cell
Animals
Humans
RNA, Messenger
Molecular Biology
Cell Proliferation
A549 cell
Membrane Potential, Mitochondrial
Cell growth
Caspase 3
Reverse Transcriptase Polymerase Chain Reaction
Epithelial Cells
Transfection
respiratory system
Xenograft Model Antitumor Assays
chemistry
Cancer research
Female
Growth inhibition
Tumor Suppressor Protein p53
Subjects
Details
- ISSN :
- 10982744
- Volume :
- 48
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular carcinogenesis
- Accession number :
- edsair.doi.dedup.....b9c850c2b323698b498a3ad2bf60c2b0