Induction of ROS-Dependent Mitochondria-Mediated Intrinsic Apoptosis in MDA-MB-231 Cells by Glycoprotein from Codium decorticatum

Abstract

Marine macroalgae consist of a range of bioactive molecules exhibiting different biological activities, and many of these properties are attributed to sulfated polysaccharides, fucoxanthin, phycobiliproteins, and halogenated compounds. In this study, a glycoprotein (GLP) with a molecular mass of ∼48 kDa was extracted and purified from Codium decorticatum and investigated for its cytotoxic properties against human MDA-MB-231 breast cancer cells. The IC₅₀ values of GLP against MDA-MB-231 and normal breast HBL-100 cells (control) were 75 ± 0.23 μg/mL (IC₂₅), 55 ± 0.32 μg/mL (IC₅₀), and 30 ± 0.43 μg/mL (IC₇₅) and 90 ± 0.57 μg/mL (IC₂₅), 80 ± 0.48 μg/mL (IC₅₀), and 60 ± 0.26 μg/mL (IC₇₅), respectively. Chromatin condensation and poly(ADP-ribose) polymerase (PARP) cleavage studies showed that the GLP inhibited cell viability by inducing apoptosis in MDA-MB-231 cells. Induction of mitochondria-mediated intrinsic apoptotic pathway by GLP was evidenced by the events of loss of mitochondrial membrane potential (ΔΨ(m)), bax/bcl-2 dysregulation, cytochrome c release, and activation of caspases 3 and 9. Apoptosis-associated factors such as reactive oxygen species (ROS) formation and loss of ΔΨ(m) were evaluated by DCFH-DA staining and flow cytometry, respectively. Cell cycle arrest of G₂/M phase and expression of apoptosis associated proteins were determined using flow cytometry and Western blotting, respectively.

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

“…These data indicate that ROS play an upstream role of caspase, AIF, Endo G and RIPK1 in SHK-induced apoptosis. ROS typically promote mitochondrial dysfunction and mitochondria-mediated apoptosis424344. We consider that ROS play an upstream role and mediate mitochondria-related apoptosis in gastric cancer cells.…”

Mitophagy Plays a Protective Role in Iodinated Contrast-Induced Acute Renal Tubular Epithelial Cells Injury

“…However, in both European Society of Urogenital Radiology and the Kidney Disease: Improving Global Outcomes guidelines, either IOCM or LOCM was recommended in patients with increased risk of CI-AKI [28, 29]. Mounting evidence demonstrated that ROS generation and mitochondrial membrane depolarization may lead to DNA damage and apoptosis [30, 31]. Recent studies indicated that an excess generation of mitochondrial ROS played an important role in the pathogenesis of AKI [32, 33].…”

Bioactive Potential of Marine Macroalgae from the Central Red Sea (Saudi Arabia) Assessed by High-Throughput Imaging-Based Phenotypic Profiling

“…Cell cycle arrest was found from fractions of one green alga (COD), two red algae (PEY1 and PEY2), as well as from the two species of the brown algal genus Cystoseira (CYS1 and CYS2). Cell cycle arrest in G2/M or the induction of apoptosis has been described from a glycoprotein of Codium decoraticum [45] as well as a cholesterol derivative from Codium sp. [42].…”