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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: 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).

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

Schematic diagram showing the possible mechanism through which GTPs inhibit melanoma cell growthInhibition of cell viability/growth by GTPs is mediated via targeting inhibition of class I HDACs proteins, promoting DNA damage and reactivation of tumor suppressor proteins.
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Figure 7: Schematic diagram showing the possible mechanism through which GTPs inhibit melanoma cell growthInhibition of cell viability/growth by GTPs is mediated via targeting inhibition of class I HDACs proteins, promoting DNA damage and reactivation of tumor suppressor proteins.

Mentions: It has been identified that cell cycle regulators are frequently mutated or deregulated in most of the human malignancies; therefore, the control of cell cycle progression in cancer cells may be an effective strategy to prevent cancer growth or progression [34-37]. Our study demonstrates that in vitro treatment of melanoma cells with GTPs decreases the expressions of cyclins and CDKs (CDK2, CDK4 and CDK6) of G1 phase in both A375 and Hs294t cell lines suggesting that GTPs induce a marked disruption of the uncontrolled cell cycle progression, and that may be a mechanism by which GTPs inhibit the proliferation or suppress the cell viability of melanoma cells. This action of GTPs is associated with the DNA damage and inhibition of HDAC activity in melanoma cells. In summary, our findings are of importance for understanding the anti-melanoma effect of GTPs, related mechanisms and clinical applications of GTPs in human system, as summarized in Figure 7. Further, the new insights into the epigenetic mechanism of action of GTPs may contribute to the chemoprevention or treatment of melanoma and may have important implications for epigenetic therapy. The use of GTPs in combination with other known HDAC inhibitors may be more effective for the treatment of melanoma and needs to be examined and explored in in vivo systems.


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)

Schematic diagram showing the possible mechanism through which GTPs inhibit melanoma cell growthInhibition of cell viability/growth by GTPs is mediated via targeting inhibition of class I HDACs proteins, promoting DNA damage and reactivation of tumor suppressor proteins.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Schematic diagram showing the possible mechanism through which GTPs inhibit melanoma cell growthInhibition of cell viability/growth by GTPs is mediated via targeting inhibition of class I HDACs proteins, promoting DNA damage and reactivation of tumor suppressor proteins.
Mentions: It has been identified that cell cycle regulators are frequently mutated or deregulated in most of the human malignancies; therefore, the control of cell cycle progression in cancer cells may be an effective strategy to prevent cancer growth or progression [34-37]. Our study demonstrates that in vitro treatment of melanoma cells with GTPs decreases the expressions of cyclins and CDKs (CDK2, CDK4 and CDK6) of G1 phase in both A375 and Hs294t cell lines suggesting that GTPs induce a marked disruption of the uncontrolled cell cycle progression, and that may be a mechanism by which GTPs inhibit the proliferation or suppress the cell viability of melanoma cells. This action of GTPs is associated with the DNA damage and inhibition of HDAC activity in melanoma cells. In summary, our findings are of importance for understanding the anti-melanoma effect of GTPs, related mechanisms and clinical applications of GTPs in human system, as summarized in Figure 7. Further, the new insights into the epigenetic mechanism of action of GTPs may contribute to the chemoprevention or treatment of melanoma and may have important implications for epigenetic therapy. The use of GTPs in combination with other known HDAC inhibitors may be more effective for the treatment of melanoma and needs to be examined and explored in in vivo systems.

Bottom Line: 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).

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