Objective:
To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been
prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)-
Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown.
Methods:
Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying
mechanisms were demonstrated at the cellular, molecular, and in vivo levels.
Results:
Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal
inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)-
Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly
(ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP
expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation
mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase
in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression
of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic
protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn
resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation
of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation
of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in
the HepG2 nude mouse model.
Conclusion:
Pt(II)-Bpy is a potential candidate for cancer chemotherapy.
Enhanced Targeting B Cell Lymphoma/Leukemia (B-L/L) by Anti-CD20 Chimeric Antigen Receptor (CAR) Modified Expanded Natural Killer (NK) Cells Combined with a Histone Deacetylase Inhibitor, Romidepsin
