Growth inhibition and apoptosis induction by (+)-Cyanidan-3-ol in hepatocellular carcinoma.

The objective of this study was to evaluate the cytotoxicity of (+)-cyanidan-3-ol (CD-3) in human hepatocellular carcinoma cell line (HepG2) and chemopreventive potential against hepatocellular carcinoma (HCC) in Balb/c mice. The HepG2 cell line was treated with CD-3 at various concentrations and th...

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Autores principales: Jitender Monga, Saurabh Pandit, Rajinder Singh Chauhan, Chetan Singh Chauhan, Shailender Singh Chauhan, Manu Sharma
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:3a539bb751cd4b34988c4ff1c8dd54a32021-11-18T09:03:12ZGrowth inhibition and apoptosis induction by (+)-Cyanidan-3-ol in hepatocellular carcinoma.1932-620310.1371/journal.pone.0068710https://doaj.org/article/3a539bb751cd4b34988c4ff1c8dd54a32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894334/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The objective of this study was to evaluate the cytotoxicity of (+)-cyanidan-3-ol (CD-3) in human hepatocellular carcinoma cell line (HepG2) and chemopreventive potential against hepatocellular carcinoma (HCC) in Balb/c mice. The HepG2 cell line was treated with CD-3 at various concentrations and the proliferation of the HepG2 cells was measure by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB) and lactate dehydrogenase (LDH) assays. Cell apoptosis was detected by Hoechst 33258 (HO), Acridine orange/ethylene dibromide (AO/EB) staining, DNA fragmentation analysis and the apoptosis rate was detected by flow cytometry. The HCC tumor model was established in mice by injecting N-nitrosodiethylamine/carbon tetrachloride (NDEA/CCl4) and the effect of CD-3 on tumor growth in-vivo was studied. The levels of liver injury markers, tumor markers, and oxidative stress were measured. The expression levels of apoptosis-related genes in in-vitro and in vivo models were determined by RT-PCR and ELISA. The CD-3 induced cell death was considered to be apoptotic by observing the typical apoptotic morphological changes under fluorescent microscopy and DNA fragmentation analysis. Annexin V/PI assay demonstrated that apoptosis increased with increase in the concentration of CD-3. The expression levels of apoptosis-related genes that belong to bcl-2 and caspase family were increased and AP-1 and NF-κB activities were significantly suppressed by CD-3. Immunohistochemistry data revealed less localization of p53, p65 and c-jun in CD-3 treated tumors as compared to localization in NDEA/CCl4 treated tumors. Taken together, our data demonstrated that CD-3 could significantly inhibit the proliferation of HepG2 cells in-vitro and suppress HCC tumor growth in-vivo by apoptosis induction.Jitender MongaSaurabh PanditRajinder Singh ChauhanChetan Singh ChauhanShailender Singh ChauhanManu SharmaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e68710 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jitender Monga
Saurabh Pandit
Rajinder Singh Chauhan
Chetan Singh Chauhan
Shailender Singh Chauhan
Manu Sharma
Growth inhibition and apoptosis induction by (+)-Cyanidan-3-ol in hepatocellular carcinoma.
description The objective of this study was to evaluate the cytotoxicity of (+)-cyanidan-3-ol (CD-3) in human hepatocellular carcinoma cell line (HepG2) and chemopreventive potential against hepatocellular carcinoma (HCC) in Balb/c mice. The HepG2 cell line was treated with CD-3 at various concentrations and the proliferation of the HepG2 cells was measure by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB) and lactate dehydrogenase (LDH) assays. Cell apoptosis was detected by Hoechst 33258 (HO), Acridine orange/ethylene dibromide (AO/EB) staining, DNA fragmentation analysis and the apoptosis rate was detected by flow cytometry. The HCC tumor model was established in mice by injecting N-nitrosodiethylamine/carbon tetrachloride (NDEA/CCl4) and the effect of CD-3 on tumor growth in-vivo was studied. The levels of liver injury markers, tumor markers, and oxidative stress were measured. The expression levels of apoptosis-related genes in in-vitro and in vivo models were determined by RT-PCR and ELISA. The CD-3 induced cell death was considered to be apoptotic by observing the typical apoptotic morphological changes under fluorescent microscopy and DNA fragmentation analysis. Annexin V/PI assay demonstrated that apoptosis increased with increase in the concentration of CD-3. The expression levels of apoptosis-related genes that belong to bcl-2 and caspase family were increased and AP-1 and NF-κB activities were significantly suppressed by CD-3. Immunohistochemistry data revealed less localization of p53, p65 and c-jun in CD-3 treated tumors as compared to localization in NDEA/CCl4 treated tumors. Taken together, our data demonstrated that CD-3 could significantly inhibit the proliferation of HepG2 cells in-vitro and suppress HCC tumor growth in-vivo by apoptosis induction.
format article
author Jitender Monga
Saurabh Pandit
Rajinder Singh Chauhan
Chetan Singh Chauhan
Shailender Singh Chauhan
Manu Sharma
author_facet Jitender Monga
Saurabh Pandit
Rajinder Singh Chauhan
Chetan Singh Chauhan
Shailender Singh Chauhan
Manu Sharma
author_sort Jitender Monga
title Growth inhibition and apoptosis induction by (+)-Cyanidan-3-ol in hepatocellular carcinoma.
title_short Growth inhibition and apoptosis induction by (+)-Cyanidan-3-ol in hepatocellular carcinoma.
title_full Growth inhibition and apoptosis induction by (+)-Cyanidan-3-ol in hepatocellular carcinoma.
title_fullStr Growth inhibition and apoptosis induction by (+)-Cyanidan-3-ol in hepatocellular carcinoma.
title_full_unstemmed Growth inhibition and apoptosis induction by (+)-Cyanidan-3-ol in hepatocellular carcinoma.
title_sort growth inhibition and apoptosis induction by (+)-cyanidan-3-ol in hepatocellular carcinoma.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/3a539bb751cd4b34988c4ff1c8dd54a3
work_keys_str_mv AT jitendermonga growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma
AT saurabhpandit growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma
AT rajindersinghchauhan growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma
AT chetansinghchauhan growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma
AT shailendersinghchauhan growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma
AT manusharma growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma
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