TY - JOUR
T1 - Decitabine augments cytotoxicity of cisplatin and doxorubicin to bladder cancer cells by activating hippo pathway through RASSF1A
AU - Khandelwal, Madhuram
AU - Anand, Vivek
AU - Appunni, Sandeep
AU - Seth, Amlesh
AU - Singh, Prabhjot
AU - Mathur, Sandeep
AU - Sharma, Alpana
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Genetic abnormalities and epigenetic alterations both play vital role in initiation as well as progression of cancer. Whereas genetic mutations cannot be reversed, epigenetic alterations such as DNA methylation can be reversed by the application of DNA methyltransferase inhibitor decitabine. Epigenetic silencing of RASSF1A and involvement of hippo pathway both have been shown to involve in chemo-resistance. Purpose of this study was to observe the effect of combination treatment of decitabine with cisplatin or doxorubicin on bladder cancer cells involving hippo pathway through RASSF1A. Bladder cancer cells (HT1376 & T24) were treated with decitabine and its effect on RASSF1A expression, hippo pathway molecules (MST & YAP), and its downstream targets (CTGF, CYR61 & CTGF) was observed. Effect of decitabine pretreatment on sensitivity of bladder cancer cells towards chemotherapeutic drugs was also studied. Decitabine treatment leads to restoration of RASSF1A, activation of hippo pathway followed by decreased expression of its oncogenic downstream targets (CTGF & CYR61). Further pretreatment of decitabine enhanced cytotoxicity of cisplatin and doxorubicin to bladder cancer cells.
AB - Genetic abnormalities and epigenetic alterations both play vital role in initiation as well as progression of cancer. Whereas genetic mutations cannot be reversed, epigenetic alterations such as DNA methylation can be reversed by the application of DNA methyltransferase inhibitor decitabine. Epigenetic silencing of RASSF1A and involvement of hippo pathway both have been shown to involve in chemo-resistance. Purpose of this study was to observe the effect of combination treatment of decitabine with cisplatin or doxorubicin on bladder cancer cells involving hippo pathway through RASSF1A. Bladder cancer cells (HT1376 & T24) were treated with decitabine and its effect on RASSF1A expression, hippo pathway molecules (MST & YAP), and its downstream targets (CTGF, CYR61 & CTGF) was observed. Effect of decitabine pretreatment on sensitivity of bladder cancer cells towards chemotherapeutic drugs was also studied. Decitabine treatment leads to restoration of RASSF1A, activation of hippo pathway followed by decreased expression of its oncogenic downstream targets (CTGF & CYR61). Further pretreatment of decitabine enhanced cytotoxicity of cisplatin and doxorubicin to bladder cancer cells.
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U2 - 10.1007/s11010-018-3278-z
DO - 10.1007/s11010-018-3278-z
M3 - Article
C2 - 29368096
AN - SCOPUS:85040953399
SN - 0300-8177
VL - 446
SP - 105
EP - 114
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -
