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Polyphenols from green tea inhibit the growth of melanoma cells through inhibition of class I histone deacetylases and induction of DNA damage.

Prasad R, Katiyar SK - Genes Cancer (2015)

Bottom Line: These effects of GTPs were associated with a significant inhibition of histone deacetylase (HDAC) activity, reduction in the levels of class I HDAC proteins, enhancement of histone acetyltransferase (HAT) activity and induction of DNA damage, as detected by Comet assay, in melanoma cells.GTPs-induced decrease in the levels of class I HDAC proteins is mediated through proteasomal degradation.Treatment of A375 and Hs294t cells with GTPs resulted in a decrease in the levels of cyclins and cyclin dependent kinases of G1 phase of cell cycle whereas upregulated the levels of tumor suppressor proteins (Cip1/WAF1/p21, p16 and p53).

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA.

ABSTRACT
Melanoma is the leading cause of skin cancer-related deaths. We have examined the effect of green tea polyphenols (GTPs), a natural mixture of epicatechin monomers, on melanoma cancer cell growth and the molecular mechanism underlying these effects using different human melanoma cell lines as an in vitro model. Treatment of melanoma cell lines (A375, Hs294t, SK-Mel28 and SK-Mel119) with GTPs significantly inhibited the cell viability as well as colony formation ability of melanoma cells in a dose-dependent manner. These effects of GTPs were associated with a significant inhibition of histone deacetylase (HDAC) activity, reduction in the levels of class I HDAC proteins, enhancement of histone acetyltransferase (HAT) activity and induction of DNA damage, as detected by Comet assay, in melanoma cells. GTPs-induced decrease in the levels of class I HDAC proteins is mediated through proteasomal degradation. Valproic acid, an inhibitor of HDACs, exhibited a similar pattern of reduced viability and induction of death of melanoma cells. Treatment of A375 and Hs294t cells with GTPs resulted in a decrease in the levels of cyclins and cyclin dependent kinases of G1 phase of cell cycle whereas upregulated the levels of tumor suppressor proteins (Cip1/WAF1/p21, p16 and p53).

No MeSH data available.


Related in: MedlinePlus

Cytotoxic effect of GTPs on melanoma cells(A) Treatment of human melanoma cells (A375, SK-Mel28, Hs294t, SK-Mel119) with various concentrations of GTPs (0, 10, 20, 40 and 60 μg/ml) inhibits the proliferation or cell viability in a dose- and time-dependent manner. Cell viability was determined using MTT assay as described in the Materials and Methods section, and data are expressed in terms of percent of control group (non-GTPs treated) as the mean ± SD of six replicates. Significant difference versus non-GTPs-treated controls, *P <0.05; †P<0.01; ¶P<0.001. (B) Treatment of melanoma cells with GTPs for 2 weeks inhibits the colony formation ability of cells. Cancer cell colonies are shown in blue-purple. (C) Number of colonies in each treatment group was detected and counted under Olympus microscope and data on colony formation are summarized in terms of percent of control. Significant difference versus control, †P<0.01, ¶P<0.001.
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Figure 1: Cytotoxic effect of GTPs on melanoma cells(A) Treatment of human melanoma cells (A375, SK-Mel28, Hs294t, SK-Mel119) with various concentrations of GTPs (0, 10, 20, 40 and 60 μg/ml) inhibits the proliferation or cell viability in a dose- and time-dependent manner. Cell viability was determined using MTT assay as described in the Materials and Methods section, and data are expressed in terms of percent of control group (non-GTPs treated) as the mean ± SD of six replicates. Significant difference versus non-GTPs-treated controls, *P <0.05; †P<0.01; ¶P<0.001. (B) Treatment of melanoma cells with GTPs for 2 weeks inhibits the colony formation ability of cells. Cancer cell colonies are shown in blue-purple. (C) Number of colonies in each treatment group was detected and counted under Olympus microscope and data on colony formation are summarized in terms of percent of control. Significant difference versus control, †P<0.01, ¶P<0.001.

Mentions: The effect of GTPs on cell viability/proliferation was determined using MTT assay as described previously [10, 21]. Melanoma cell lines, A375, SK-Mel28, Hs294t and SK-Mel 119, were treated with different concentrations of GTPs (0, 10, 20, 40, and 60 μg/ml) for 24 and 48 h. As shown in Fig. 1A, treatment of melanoma cells with GTPs resulted in significant reduction of the cell viability: A375 (12-34% at 24 h and 18-49% at 48 h), SK-Mel 28 (7-29% at 24 h and 9-50% at 48 h), Hs294t (6-45% at 24 h and 13-72% at 48 h), and SK-Mel 119 (6-32% at 24 h and 14-49% at 48 h). The inhibitory effect of GTPs on melanoma cells growth was also verified and tested using colony formation assay, as shown in Fig. 1B. The colonies are shown in purple-dark blue. The individual colonies were counted under microscope and resultant data on colony formation are summarized in Fig. 1C in terms of percent of control (non-GTPs-treated group). As shown in Fig. 1C, treatment of different melanoma cell lines with various concentrations of GTPs significantly inhibited (P<0.01, P<0.001) the colony formation ability in each melanoma cell line compared with control group (non-GTPs-treated cells). Moreover, the size of the colonies was smaller in GTPs-treated cells compared to control group. These results indicate the cytotoxic action of GTPs in melanoma cells. Importantly, treatment of NHM with GTPs did not result in significant inhibition of cell viability under identical experimental conditions [22].


Polyphenols from green tea inhibit the growth of melanoma cells through inhibition of class I histone deacetylases and induction of DNA damage.

Prasad R, Katiyar SK - Genes Cancer (2015)

Cytotoxic effect of GTPs on melanoma cells(A) Treatment of human melanoma cells (A375, SK-Mel28, Hs294t, SK-Mel119) with various concentrations of GTPs (0, 10, 20, 40 and 60 μg/ml) inhibits the proliferation or cell viability in a dose- and time-dependent manner. Cell viability was determined using MTT assay as described in the Materials and Methods section, and data are expressed in terms of percent of control group (non-GTPs treated) as the mean ± SD of six replicates. Significant difference versus non-GTPs-treated controls, *P <0.05; †P<0.01; ¶P<0.001. (B) Treatment of melanoma cells with GTPs for 2 weeks inhibits the colony formation ability of cells. Cancer cell colonies are shown in blue-purple. (C) Number of colonies in each treatment group was detected and counted under Olympus microscope and data on colony formation are summarized in terms of percent of control. Significant difference versus control, †P<0.01, ¶P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4362484&req=5

Figure 1: Cytotoxic effect of GTPs on melanoma cells(A) Treatment of human melanoma cells (A375, SK-Mel28, Hs294t, SK-Mel119) with various concentrations of GTPs (0, 10, 20, 40 and 60 μg/ml) inhibits the proliferation or cell viability in a dose- and time-dependent manner. Cell viability was determined using MTT assay as described in the Materials and Methods section, and data are expressed in terms of percent of control group (non-GTPs treated) as the mean ± SD of six replicates. Significant difference versus non-GTPs-treated controls, *P <0.05; †P<0.01; ¶P<0.001. (B) Treatment of melanoma cells with GTPs for 2 weeks inhibits the colony formation ability of cells. Cancer cell colonies are shown in blue-purple. (C) Number of colonies in each treatment group was detected and counted under Olympus microscope and data on colony formation are summarized in terms of percent of control. Significant difference versus control, †P<0.01, ¶P<0.001.
Mentions: The effect of GTPs on cell viability/proliferation was determined using MTT assay as described previously [10, 21]. Melanoma cell lines, A375, SK-Mel28, Hs294t and SK-Mel 119, were treated with different concentrations of GTPs (0, 10, 20, 40, and 60 μg/ml) for 24 and 48 h. As shown in Fig. 1A, treatment of melanoma cells with GTPs resulted in significant reduction of the cell viability: A375 (12-34% at 24 h and 18-49% at 48 h), SK-Mel 28 (7-29% at 24 h and 9-50% at 48 h), Hs294t (6-45% at 24 h and 13-72% at 48 h), and SK-Mel 119 (6-32% at 24 h and 14-49% at 48 h). The inhibitory effect of GTPs on melanoma cells growth was also verified and tested using colony formation assay, as shown in Fig. 1B. The colonies are shown in purple-dark blue. The individual colonies were counted under microscope and resultant data on colony formation are summarized in Fig. 1C in terms of percent of control (non-GTPs-treated group). As shown in Fig. 1C, treatment of different melanoma cell lines with various concentrations of GTPs significantly inhibited (P<0.01, P<0.001) the colony formation ability in each melanoma cell line compared with control group (non-GTPs-treated cells). Moreover, the size of the colonies was smaller in GTPs-treated cells compared to control group. These results indicate the cytotoxic action of GTPs in melanoma cells. Importantly, treatment of NHM with GTPs did not result in significant inhibition of cell viability under identical experimental conditions [22].

Bottom Line: These effects of GTPs were associated with a significant inhibition of histone deacetylase (HDAC) activity, reduction in the levels of class I HDAC proteins, enhancement of histone acetyltransferase (HAT) activity and induction of DNA damage, as detected by Comet assay, in melanoma cells.GTPs-induced decrease in the levels of class I HDAC proteins is mediated through proteasomal degradation.Treatment of A375 and Hs294t cells with GTPs resulted in a decrease in the levels of cyclins and cyclin dependent kinases of G1 phase of cell cycle whereas upregulated the levels of tumor suppressor proteins (Cip1/WAF1/p21, p16 and p53).

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA.

ABSTRACT
Melanoma is the leading cause of skin cancer-related deaths. We have examined the effect of green tea polyphenols (GTPs), a natural mixture of epicatechin monomers, on melanoma cancer cell growth and the molecular mechanism underlying these effects using different human melanoma cell lines as an in vitro model. Treatment of melanoma cell lines (A375, Hs294t, SK-Mel28 and SK-Mel119) with GTPs significantly inhibited the cell viability as well as colony formation ability of melanoma cells in a dose-dependent manner. These effects of GTPs were associated with a significant inhibition of histone deacetylase (HDAC) activity, reduction in the levels of class I HDAC proteins, enhancement of histone acetyltransferase (HAT) activity and induction of DNA damage, as detected by Comet assay, in melanoma cells. GTPs-induced decrease in the levels of class I HDAC proteins is mediated through proteasomal degradation. Valproic acid, an inhibitor of HDACs, exhibited a similar pattern of reduced viability and induction of death of melanoma cells. Treatment of A375 and Hs294t cells with GTPs resulted in a decrease in the levels of cyclins and cyclin dependent kinases of G1 phase of cell cycle whereas upregulated the levels of tumor suppressor proteins (Cip1/WAF1/p21, p16 and p53).

No MeSH data available.


Related in: MedlinePlus