Title:Cytotoxic Activity of a Unique Monomeric Heterogeneous Two-Coordinate
Ligand Monovalent Gold Complex with Tiopronin and a Heterocyclic
Mercapto-Tetrazole Compound
Volume: 29
Issue: 22
关键词:
金配合物，tpn-au[I]-mm4，辐射致敏效应，人类 thp1 细胞，抑制增殖，诱导细胞死亡
摘要:
Background: The importance of the role of NF-κB is recognized in situations
such as malignant transformation and metastasis of cancer, and it has been suggested that
inhibiting this role can be one of the cancer treatment strategies. Gold preparations such
as auranofin are known to have an indirect NF-κB inhibitory effect.
Objective: We synthesized a novel gold complex [tiopronin monovalent gold-5-mercapto-
1-methyl tetrazole, abbreviated as TPN-Au(I)-MM4], with different physical properties
and chemical structure from auranofin, and evaluated its cytotoxic activity and radiation
sensitizing effect on human THP1 cells.
Methods: The number of viable cells was counted by the trypan blue dye exclusion
method. The cell death evaluation was performed by FITC-Annexin V+ and PI staining.
In investigating the radiation sensitizing effect of TPN-Au(I)-MM4, this compound [10
or 25 μM] was added into the culture medium 1 h before X-ray irradiation.
Results: In the cells treated with 25 μM TPN-Au(I)-MM4 for 72 h, a decrease in the proliferation
of THP1 cells was observed [The relative values of viable cells in the control
group and the 25 μM treatment group were approximately 6.8 and 4.2, respectively]. In
the combination of 25 μM of the compound treatment and X-ray irradiation, an increase
of approximately 3.0-fold was observed in 2 Gy irradiation and approximately 1.4-fold in
4 Gy irradiation as in comparison to the case of irradiation alone.
Conclusion: These results suggest that TPN-Au(I)-MM4 reduces the proliferation of THP1
cells through the induction of cell death, and the combined use of TPN-Au(I)-MM4
and X-ray irradiation shows effective cytotoxicity against THP1 cells.
