Related Experiment Video
Updated: Aug 14, 2025
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Nickel chloride induces anticancer biological responses in hepatocellular carcinoma cell lines
Erkan Kahraman1,2, Erdem Goker1,3
1Research and Application Center of Individualized Medicine, 60521Ege University, Izmir, Turkey.
Abstract:
Nickel has long been known to have a toxic effect in humans and has been defined as a human carcinogen. However, recent studies have suggested that nickel chloride (NiCl2) may also possess anticancer properties. The liver is one of the target organs for nickel, and thus, the present study aims to evaluate the effect of NiCl2 on anticancer biological responses in hepatocellular carcinoma (HCC) cell lines. Both HuH-7, a well-differentiated HCC cell line, and Mahlavu cell line, a poorly differentiated HCC cell line, were exposed to NiCl2. It was determined that NiCl2 decreased cell viability in both cell lines in a dose- and time-dependent manner. Nickel chloride exposure at IC50 doses were observed to suppress the ability of HCC cells to produce colonies and also induce apoptosis of HCC cells by increasing Cleaved Caspase-3 protein levels. It was found that NiCl2 exposure affected cellular morphology, increased the LC3-II protein levels, and induced autophagy in parallel to increased apoptosis in HCC cells. It was also observed that NiCl2 suppressed cell migration, decreased the size and viability of HCC tumor spheroids generated in 3D cell cultures, and disrupted the spheroid structure of the tumor cells depending on E-cadherin expression levels. Furthermore, it was observed that all anticancer biological responses induced by NiCl2 occurred independently of the AKT signaling pathway. In conclusion, our results suggested that NiCl2 induced anticancer biological responses in HCC cell lines. Moreover, this study provided important new molecular and cellular biological basic data about the action mechanisms of NiCl2 in HCC.
Insights
Nickel chloride (NiCl2) shows anticancer effects against hepatocellular carcinoma (HCC) cells. This study found NiCl2 suppresses HCC cell viability, colony formation, migration, and induces apoptosis and autophagy, independent of the AKT pathway.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Nickel is a known human carcinogen.
- Emerging research suggests nickel chloride (NiCl2) may have anticancer properties.
- The liver is a target organ for nickel toxicity.
Purpose of the Study:
- To investigate the anticancer effects of NiCl2 on hepatocellular carcinoma (HCC) cell lines.
- To evaluate the impact of NiCl2 on cell viability, apoptosis, autophagy, and migration in HCC.
- To explore the underlying molecular mechanisms of NiCl2's action in HCC.
Main Methods:
- Exposure of HuH-7 and Mahlavu HCC cell lines to varying doses and times of NiCl2.
- Assessment of cell viability, colony formation, and apoptosis (Cleaved Caspase-3 levels).
- Analysis of cellular morphology, autophagy (LC3-II levels), cell migration, and 3D tumor spheroid behavior.
Main Results:
- NiCl2 significantly decreased HCC cell viability, colony formation, and migration in a dose- and time-dependent manner.
- NiCl2 induced apoptosis and autophagy in HCC cells, evidenced by increased Cleaved Caspase-3 and LC3-II protein levels.
- NiCl2 disrupted HCC tumor spheroid structure and viability, with effects correlating to E-cadherin expression, independent of the AKT signaling pathway.
Conclusions:
- NiCl2 exhibits significant anticancer biological responses in HCC cell lines.
- NiCl2 induces apoptosis and autophagy, suppresses proliferation and migration, and affects tumor spheroid development in HCC.
- The anticancer effects of NiCl2 in HCC occur independently of the AKT signaling pathway, providing novel insights into its mechanism of action.
