Betula etnensis Raf. (Betulaceae) Extract Induced HO-1 Expression and Ferroptosis Cell Death in Human Colon Cancer Cells

Abstract

Betula etnensis Raf. (Birch Etna) belonging to the Betulaceae family grows on the eastern slope of Etna. Many bioactive compounds present in Betula species are considered promising anticancer agents. In this study, we evaluated the effects of B. etnensis Raf. bark methanolic extract on a human colon cancer cell line (CaCo2). In order to elucidate the mechanisms of action of the extract, cellular redox status, cell cycle, and heme oxygenase-1 (HO-1) expression in ferroptosis induction were evaluated. Cell viability and proliferation were tested by tetrazolium (MTT) assayand cell cycle analysis, while cell death was evaluated by annexin V test and lactic dehydrogenase (LDH) release. Cellular redox status was assessed by measuring thiol groups (RSH) content, reactive oxygen species (ROS) production, lipid hydroperoxide (LOOH) levels and (γ-glutamylcysteine synthetase) γ-GCS and HO-1 expressions. The extract significantly reduced cell viability of CaCo2, inducing necrotic cell death in a concentration-depending manner. In addition, an increase in ROS levels and a decrease of RSH content without modulation in γ-GCS expression were detected, with an augmentation in LOOH levels and drastic increase in HO-1 expression. These results suggest that the B. etnensis Raf. extract promotes an oxidative cellular microenvironment resulting in CaCo2 cell death by ferroptosis mediated by HO-1 hyper-expression.

Brassica incana Ten. (Brassicaceae): Phenolic Constituents, Antioxidant and Cytotoxic Properties of the Leaf and Flowering Top Extracts

“…LDH is a soluble cytoplasmic enzyme that is present in almost all cells and is released into extracellular space due to the loss of membrane integrity in dying cells. Thus, the determination of LDH release can be utilized as a useful method for detection of necrosis, and therefore as a measure of cytotoxicity [45,46]. The capacity of a plant extract to induce necrotic cell death could potentially be a valuable adjunctive therapy in cancer treatment [47].…”

Rapha Myr®, a Blend of Sulforaphane and Myrosinase, Exerts Antitumor and Anoikis-Sensitizing Effects on Human Astrocytoma Cells Modulating Sirtuins and DNA Methylation

“…Cell cycle analysis was performed on untreated and 24 h treated cells with Rapha Myr ® extract (0.5–1.25–2.5% v/v ), according to Malfa et al, 2019 [ 70 ]. In order to assess cell cycle state, 1 × 10 6 cells were stained with propidium iodide (PI, 50 ng/mL) and analyzed by the FlowSight ® (Amnis ® , part of EMD Millipore) imaging flow cytometer.…”

Association of oral dysbiosis with oral cancer development (Review)

“…It has been widely demonstrated that environmental factors, including diet, lifestyle habits, and natural compounds, are responsible for both genetic and epigenetic alterations predisposing the development of several diseases, and have beneficial effects in preventing the development of chronic-degenerative disorders (133)(134)(135)(136)(137)(138)(139)(140). In particular, dietary intake and food consumption modulate several cellular and molecular processes acting in a multifactorial manner (141)(142)(143). Indeed, the consumption of specific food and nutrients may modulate inflammatory and cell cycle regulatory pathways to maintain the optimal cell homeostasis, preventing the development of diseases (144,145).…”