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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.
Mol Carcinog. 2009 Jan; 48(1):24-37.MC

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.

Authors+Show Affiliations

Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18459128

Citation

Katiyar, Santosh K., et al. "P53 Cooperates Berberine-induced Growth Inhibition and Apoptosis of Non-small Cell Human Lung Cancer Cells in Vitro and Tumor Xenograft Growth in Vivo." Molecular Carcinogenesis, vol. 48, no. 1, 2009, pp. 24-37.
Katiyar SK, Meeran SM, Katiyar N, et al. P53 Cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo. Mol Carcinog. 2009;48(1):24-37.
Katiyar, S. K., Meeran, S. M., Katiyar, N., & Akhtar, S. (2009). P53 Cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo. Molecular Carcinogenesis, 48(1), 24-37. https://doi.org/10.1002/mc.20453
Katiyar SK, et al. P53 Cooperates Berberine-induced Growth Inhibition and Apoptosis of Non-small Cell Human Lung Cancer Cells in Vitro and Tumor Xenograft Growth in Vivo. Mol Carcinog. 2009;48(1):24-37. PubMed PMID: 18459128.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p53 Cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo. AU - Katiyar,Santosh K, AU - Meeran,Syed M, AU - Katiyar,Nandan, AU - Akhtar,Suhail, PY - 2008/5/7/entrez PY - 2008/5/7/pubmed PY - 2009/7/16/medline SP - 24 EP - 37 JF - Molecular carcinogenesis JO - Mol Carcinog VL - 48 IS - 1 N2 - 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. SN - 1098-2744 UR - https://www.unboundmedicine.com/medline/citation/18459128/p53_Cooperates_berberine_induced_growth_inhibition_and_apoptosis_of_non_small_cell_human_lung_cancer_cells_in_vitro_and_tumor_xenograft_growth_in_vivo_ L2 - https://doi.org/10.1002/mc.20453 DB - PRIME DP - Unbound Medicine ER -