The copper (II) complex of salicylate phenanthroline inhibits proliferation and induces apoptosis of hepatocellular carcinoma cells

Abstract

In the present study, we investigated the antitumor effect and associated molecular mechanisms of the copper (II) complex of salicylate phenanthroline [Cu(sal)(phen)] against hepatocellular carcinoma (HCC). Cu(sal)(phen) inhibited the proliferation of HCC cells (HepG2 and HCC‐LM9) and induced apoptosis of HCC cells in a dose‐dependent manner by upregulating mitochondrial reactive oxygen species (ROS) production. The expression of the antiapoptotic proteins survivin and Bcl‐2 was decreased, while the expression of the DNA damage marker γ‐H2AX and the apoptotic marker cleaved PARP was upregulated with Cu(sal)(phen) treatment. In vivo, the growth of HepG2 subcutaneous xenograft tumors was greatly attenuated by Cu(sal)(phen) treatment. Immunohistochemistry staining showed that the expression of survivin, Bcl‐2, and Ki67 in the tumor was downregulated by Cu(sal)(phen). Toxicity experiments with BALB/c mice revealed that Cu(sal)(phen) is a relatively safe drug. Our results indicate that Cu(sal)(phen) possesses great potential as a therapeutic drug for HCC.

Copper (II) complex of salicylate phenanthroline induces the apoptosis of colorectal cancer cells, including oxaliplatin‑resistant cells

“…In conclusion, the findings of the present study suggest that Cu(sal)(phen) inhibits the proliferation and induces the apoptosis of CRC cells in vitro, while also inhibiting tumor growth in vivo in nude mice. In addition, Cu (sal) (phen) was shown to have a good safety profile in previous in vivo experiments on Balb/c mice (53). The underlying mechanisms of Cu(sal) (phen) treatment involve the induction of ROS generation, the inhibition of the JAK2/STAT5 signaling pathway and the downregulation of the expression of anti-apoptotic proteins, such as Bcl-2 and survivin.…”