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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894334/pdf/?tool=EBI |
| _version_ | 1818337483198300160 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T14:55:56Z |
| format | Article |
| id | doaj.art-3a539bb751cd4b34988c4ff1c8dd54a3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T14:55:56Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3a539bb751cd4b34988c4ff1c8dd54a32022-12-21T23:41:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6871010.1371/journal.pone.0068710Growth inhibition and apoptosis induction by (+)-Cyanidan-3-ol in hepatocellular carcinoma.Jitender MongaSaurabh PanditRajinder Singh ChauhanChetan Singh ChauhanShailender Singh ChauhanManu SharmaThe 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894334/pdf/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894334/pdf/?tool=EBI |
| work_keys_str_mv | AT jitendermonga growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma AT saurabhpandit growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma AT rajindersinghchauhan growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma AT chetansinghchauhan growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma AT shailendersinghchauhan growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma AT manusharma growthinhibitionandapoptosisinductionbycyanidan3olinhepatocellularcarcinoma |