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2012 ; 15
(3
): 31-8
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Involvement of Transient Receptor Potential Melastatin 7 Channels in Sophorae
Radix-induced Apoptosis in Cancer Cells: Sophorae Radix and TRPM7
#MMPMID25780645
Kim BJ
J Pharmacopuncture
2012[Sep]; 15
(3
): 31-8
PMID25780645
show ga
Sophorae Radix (SR) plays a role in a number of physiologic and pharmacologic
functions in many organs. OBJECTIVE: The aim of this study was to clarify the
potential role for transient receptor potential melastatin 7 (TRPM7) channels in
SR-inhibited growth and survival of AGS and MCF-7 cells, the most common human
gastric and breast adenocarcinoma cell lines. METHODS: The AGS and the MCF-7
cells were treated with varying concentrations of SR. Analyses of the caspase-3
and - 9 activity, the mitochondrial depolarization and the poly (ADPribose)
polymerase (PARP) cleavage were conducted to determine if AGS and MCF-7 cell
death occured by apoptosis. TRPM7 channel blockers (Gd(3+) or 2-APB) and small
interfering RNA (siRNA) were used in this study to confirm the role of TRPM7
channels. Furthermore, TRPM7 channels were overexpressed in human embryonic
kidney (HEK) 293 cells to identify the role of TRPM7 channels in AGS and MCF-7
cell growth and survival. RESULTS: The addition of SR to a culture medium
inhibited AGS and MCF-7 cell growth and survival. Experimental results showed
that the caspase-3 and -9 activity, the mitochondrial depolarization, and the
degree of PARP cleavage was increased. TRPM7 channel blockade, either by Gd(3+)
or 2-APB or by suppressing TRPM7 expression with small interfering RNA, blocked
the SR-induced inhibition of cell growth and survival. Furthermore, TRPM7 channel
overexpression in HEK 293 cells exacerbated SR-induced cell death. CONCLUSIONS:
These findings indicate that SR inhibits the growth and survival of gastric and
breast cancer cells due to a blockade of the TRPM7 channel activity. Therefore,
TRPM7 channels may play an important role in the survival of patients with
gastric and breast cancer.