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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

Treatment of A375 and Hs294t melanoma cell lines with GTPs for 48 h resulted in reactivation of tumor suppressor proteins and affects the cell cycle regulatory proteins of G1 phaseMelanoma cell lines (A375 and Hs294t) were treated with various concentrations of GTPs for 48 h; then cells were harvested for cell lysates, which were subjected to western blot analysis. (A) Treatment of cells with GTPs enhances or reactivated the expressions of tumor suppressor proteins, such as p53, Cip1/WAF1/p21 and p16. (B) Treatment of cells with GTPs inhibits the levels of cyclins and CDKs associated with the G1 phase of the cell cycle in a dose-dependent manner, as analyzed by western blotting. Equal loading of protein samples was verified using anti-β-actin antibody. Representative blots are shown.
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Figure 5: Treatment of A375 and Hs294t melanoma cell lines with GTPs for 48 h resulted in reactivation of tumor suppressor proteins and affects the cell cycle regulatory proteins of G1 phaseMelanoma cell lines (A375 and Hs294t) were treated with various concentrations of GTPs for 48 h; then cells were harvested for cell lysates, which were subjected to western blot analysis. (A) Treatment of cells with GTPs enhances or reactivated the expressions of tumor suppressor proteins, such as p53, Cip1/WAF1/p21 and p16. (B) Treatment of cells with GTPs inhibits the levels of cyclins and CDKs associated with the G1 phase of the cell cycle in a dose-dependent manner, as analyzed by western blotting. Equal loading of protein samples was verified using anti-β-actin antibody. Representative blots are shown.

Mentions: As the treatment of melanoma cells with GTPs resulted in a reduction in Class I HDAC protein expression, DNA damage and cell viability, we next determined whether this effect of GTPs on melanoma cells is associated with deregulation of cell cycle regulatory proteins. For this purpose the effect of GTPs was determined on cell cycle regulatory proteins in A375 and Hs294t cells following treatment of cells with GTPs for 48 h. As shown in Figure 5B, the analysis of cell cycle proteins of G1 phase revealed that treatment of A375 and Hs294t cells with GTPs resulted in inhibition of cyclin D1, cyclin D2 and cyclin E proteins expressions in a dose-dependent manner. Similarly, a marked reduction in the expression of CDK2, CDK4 and CDK6 proteins was observed (Figure 5B). Inhibitory effect of GTPs on cyclins and CDKs of G1 phase in both melanoma cell lines was almost identical. These results suggest that GTPs induce deregulation of G1 phase cell cycle proteins following DNA damage in melanoma cell lines.


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)

Treatment of A375 and Hs294t melanoma cell lines with GTPs for 48 h resulted in reactivation of tumor suppressor proteins and affects the cell cycle regulatory proteins of G1 phaseMelanoma cell lines (A375 and Hs294t) were treated with various concentrations of GTPs for 48 h; then cells were harvested for cell lysates, which were subjected to western blot analysis. (A) Treatment of cells with GTPs enhances or reactivated the expressions of tumor suppressor proteins, such as p53, Cip1/WAF1/p21 and p16. (B) Treatment of cells with GTPs inhibits the levels of cyclins and CDKs associated with the G1 phase of the cell cycle in a dose-dependent manner, as analyzed by western blotting. Equal loading of protein samples was verified using anti-β-actin antibody. Representative blots are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4362484&req=5

Figure 5: Treatment of A375 and Hs294t melanoma cell lines with GTPs for 48 h resulted in reactivation of tumor suppressor proteins and affects the cell cycle regulatory proteins of G1 phaseMelanoma cell lines (A375 and Hs294t) were treated with various concentrations of GTPs for 48 h; then cells were harvested for cell lysates, which were subjected to western blot analysis. (A) Treatment of cells with GTPs enhances or reactivated the expressions of tumor suppressor proteins, such as p53, Cip1/WAF1/p21 and p16. (B) Treatment of cells with GTPs inhibits the levels of cyclins and CDKs associated with the G1 phase of the cell cycle in a dose-dependent manner, as analyzed by western blotting. Equal loading of protein samples was verified using anti-β-actin antibody. Representative blots are shown.
Mentions: As the treatment of melanoma cells with GTPs resulted in a reduction in Class I HDAC protein expression, DNA damage and cell viability, we next determined whether this effect of GTPs on melanoma cells is associated with deregulation of cell cycle regulatory proteins. For this purpose the effect of GTPs was determined on cell cycle regulatory proteins in A375 and Hs294t cells following treatment of cells with GTPs for 48 h. As shown in Figure 5B, the analysis of cell cycle proteins of G1 phase revealed that treatment of A375 and Hs294t cells with GTPs resulted in inhibition of cyclin D1, cyclin D2 and cyclin E proteins expressions in a dose-dependent manner. Similarly, a marked reduction in the expression of CDK2, CDK4 and CDK6 proteins was observed (Figure 5B). Inhibitory effect of GTPs on cyclins and CDKs of G1 phase in both melanoma cell lines was almost identical. These results suggest that GTPs induce deregulation of G1 phase cell cycle proteins following DNA damage in melanoma cell lines.

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