Switching p53-dependent growth arrest to apoptosis via the inhibition of DNA damage-activated kinases

• Autorzy: Hublarova P , Greplova K. , Holcakova J. , Vojtesek B. , Hrstka R.
• Języki publikacji: EN

Abstrakty

EN

Cisplatin and doxorubicin are widely used anticancer drugs that cause DNA damage, which activates the ATM-Chk2-p53 pathway in cancer cells. This activation leads to cell cycle block or apoptosis, depending on the nature of the DNA damage. In an attempt to enhance the effects of these agents, we inhibited ATM/ATR and Chk2, which are known upstream regulators of p53. The cancer cell lines A2780 and ARN8, bearing the wild-type p53 protein, were used to study changes in p53 activation and trans-activation. Our results suggest that the G1-checkpoint, normally activated by DNA damage, is functionally overcome by the action of kinase inhibitors that sensitize cells to apoptosis. Both inhibitors show these effects, albeit with variable intensity in different cell lines, which is promising for other studies and theoretically for use in clinical practice.

Słowa kluczowe

EN

p53 protein; apoptosis; inhibition; DNA damage-activated kinase; doxorubicin; cisplatin; anticancer drug; drug; cancer cell

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2010
• Tom: 15
• Numer: 3
• Opis fizyczny: p.473-484,fig.,ref.

Twórcy

autor

Hublarova P

• Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 53, Brno, Czech Republic

autor

Greplova K.

autor

Holcakova J.

autor

Vojtesek B.

autor

Hrstka R.

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