Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma Cells

Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fourth cause of cancer-related deaths worldwide. Presently, a few drugs are available for HCC treatment and prevention, including both natural and synthetic compounds. In this study, a new chalcone, (E)-1-(2,4,6-triethoxyphenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (ETTC), was synthesized and its effects and mechanisms of action over human hepatoma cells were investigated. Cytotoxic activity was revealed in HCC cells, while no effects were observed in normal hepatocytes. In HCC cells, ETTC caused subG1 cell cycle arrest and apoptosis, characterized by nuclear fragmentation. The activation of caspases 3/7 and 9, the increase in pro-apoptotic BAX, and the decrease in anti-apoptotic BCL-2 suggest the activation of the intrinsic pathway of apoptosis. ETTC mitochondrial targeting is confirmed by the reduction in mitochondrial membrane potential and Complex I activity together with levels of superoxide anion increasing. Our outcomes prove the potential mitochondria-mediated antitumor effect of newly synthesized chalcone ETTC in HCC.

Effects of Extracts of Two Selected Strains of Haematococcus pluvialis on Adipocyte Function

“…To measure cell viability, 0, 20, 50 and 100 μg/mL of HP Wt, FBR1 and FBR2 were added to 3T3-L1 adipocytes for 24, 48 and 72 h. A CellTiter-Glo ® 2.0 Cell Viability Assay (G9242 Promega, Madison, WI, USA) was used to measure cell proliferation, as previously reported [ 38 ]. Briefly, after 10 min of incubation at room temperature, the luminescence was measured using a microplate reader (GloMax, Promega,).…”

Targeting STAT3 and NF-κB Signaling Pathways in Cancer Prevention and Treatment: The Role of Chalcones

“…Therefore, new chalcone derivatives are still being sought, whose structure, improved by chemical synthesis, could show a broader or more specific spectrum of activity toward human cells [ 16 ].…”

“…Natural chalcones have attracted particular attention from scientists due to their wide range of biological activity and potential therapeutic use. Unfortunately, they do not accumulate in plants in large quantities because they are used as intermediates for the biosynthesis of flavonoids, which generates a problem with obtaining them in the necessary amounts [ 16 , 17 ].…”

“…The limitations of using natural chalcones are their low solubility in water, poor absorption, and short residence time in the intestine. For these reasons, research is being conducted on modifying the molecular structure of these compounds, which would allow for obtaining derivatives with better physicochemical and biological properties [ 16 , 18 ].…”

Loss of the Novel Mitochondrial Membrane Protein FAM210B Is Associated with Hepatocellular Carcinoma

“…Given that preventing and diagnosing liver cancer remains a difficult task, identifying effective markers would be of significant benefit. Moreover, by examining gene networks for changes associated with malignant behavior and progression, it may be possible to determine the fundamental mechanisms of key biomarkers that underlie HCC pathophysiology or targets for HCC therapy [ 10 , 11 ]. This could lead to the development of novel treatment modalities.…”