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

Monga J, Pandit S, Chauhan RS, Chauhan CS, Chauhan SS, Sharma M - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, Himachal Pradesh, India.

ABSTRACT
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.

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Related in: MedlinePlus

Chemical structure of (+)-cyanidan-3-ol.
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pone-0068710-g001: Chemical structure of (+)-cyanidan-3-ol.

Mentions: In recent years, the number of natural products has acquired a lot of attention because of their ability to provide prevention and therapeutic efficacy against number of cancers [3]. Out of number of different classes of natural products, flavonoids represent a diverse group of low molecular weight polyphenolic compounds that are widely distributed in nature and renewed interest has been observed in recent years in the novel and multiple activities of flavonoids [4]. Acaciacatechu Willd. (Fabaceae) also known as ‘Khadira’ has been extensively used as traditional medicine in India/Asia over a long period of time and a rich source of number of polyphenolic compounds. Previously, we have reported chemopreventive effect of aqueous extract of Acaciacatechu in skin and mammary cancer rodent models [5,6]. (+)-Cyanidan-3-ol (CD-3) [3',4',5,7-tetrahydroxyflavan-3-ol] (Figure 1) is the most abundant polyphenolic flavonoid in the Acaciacatechu heartwood and studies of the biological effects of CD-3 in cell culture and in vivo models indicated that this compound can inhibit lipid peroxidation [7]. CD-3 is claimed to be effective in treating carbon tetrachloride induced liver damage [8] and also reported to inhibit angiogenesis in-vivo [9]. However, there is no report on the effect of CD-3 on hepatocellular carcinoma (HCC). In this paper, we report the chemopreventive and therapeutic efficacy of CD-3 against hepatocellular carcinoma by using both in-vitro and in vivo systems. Further, the underlying cellular andmolecular mechanisms of CD-3 actions were also evaluated. Our data provided investigational evidence to carry the potential development of CD-3 as an efficient and safe candidate for the prevention and/or therapy of liver cancer.


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

Monga J, Pandit S, Chauhan RS, Chauhan CS, Chauhan SS, Sharma M - PLoS ONE (2013)

Chemical structure of (+)-cyanidan-3-ol.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3722203&req=5

pone-0068710-g001: Chemical structure of (+)-cyanidan-3-ol.
Mentions: In recent years, the number of natural products has acquired a lot of attention because of their ability to provide prevention and therapeutic efficacy against number of cancers [3]. Out of number of different classes of natural products, flavonoids represent a diverse group of low molecular weight polyphenolic compounds that are widely distributed in nature and renewed interest has been observed in recent years in the novel and multiple activities of flavonoids [4]. Acaciacatechu Willd. (Fabaceae) also known as ‘Khadira’ has been extensively used as traditional medicine in India/Asia over a long period of time and a rich source of number of polyphenolic compounds. Previously, we have reported chemopreventive effect of aqueous extract of Acaciacatechu in skin and mammary cancer rodent models [5,6]. (+)-Cyanidan-3-ol (CD-3) [3',4',5,7-tetrahydroxyflavan-3-ol] (Figure 1) is the most abundant polyphenolic flavonoid in the Acaciacatechu heartwood and studies of the biological effects of CD-3 in cell culture and in vivo models indicated that this compound can inhibit lipid peroxidation [7]. CD-3 is claimed to be effective in treating carbon tetrachloride induced liver damage [8] and also reported to inhibit angiogenesis in-vivo [9]. However, there is no report on the effect of CD-3 on hepatocellular carcinoma (HCC). In this paper, we report the chemopreventive and therapeutic efficacy of CD-3 against hepatocellular carcinoma by using both in-vitro and in vivo systems. Further, the underlying cellular andmolecular mechanisms of CD-3 actions were also evaluated. Our data provided investigational evidence to carry the potential development of CD-3 as an efficient and safe candidate for the prevention and/or therapy of liver cancer.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, Himachal Pradesh, India.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus