Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells

Abstract

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4′-trimethoxy-2′-hydroxy-chalcone (CH1) and 3′-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

Anti-growth Effects of Imatinib and GNF5 via Regulation of Skp2 in Human Hepatocellular Carcinoma Cells

“…Among the caspases that function as important regulators of apoptosis, caspase-3, a major effector in apoptosis progression, interacts with caspase-9 and caspase-8. In previous studies using HCC cells, the activation of caspase-9, caspase-8 and caspase-3 was investigated to evalutate caspase-dependent apoptosis 16,17. We found that imatinib and GNF5 induced caspase-mediated apoptosis, and slightly increased p27 and p21 protein level in SK-HEP1 cells.…”

Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

“…Among these, apoptosis and necrosis are the most common and studied ones. Apoptosis events have been induced by chalcones towards different cancer cell lines 36,37 . In order to investigate antiproliferative effect mechanism of selected chalcones 11 and 17 towards MCF-7 and MDA-MB-231 lines, Annexin V/PI staining and flow cytometry were used to detect whether cells were dying due to apoptosis or necrosis events (Figure 2).…”

Synthesis of Novel Thiophene‐Chalcone Derivatives as Anticancer‐ and Apoptosis‐Inducing Agents

“…The vital roles of chalcones include anticancer activity, anti‐inflammatory activity, antibacterial activity, antituberculosis activity, antidiabetic activity, antioxidant activity, antimicrobial activity, antiviral activity, antimalarial activity, neuroprotective effects, and others . Although, chalcones show antiproliferative activity through up regulation of caspase signaling cascade that will activate the mitochondrial intrinsic pathways and promotes apoptotic cell death, recent investigation suggest that chalcones enhance the cancer cell death though the G0/G1 and S phase arrest . In continuation of our work, we reported novel thiophene based chalcone scaffolds as apoptosis‐inducing anticancer agents in cancer therapy (Figure ).…”