Ethanol Extract of Hizikia fusiforme Induces Apoptosis in B16F10 Mouse Melanoma Cells through ROS-Dependent Inhibition of the PI3K/Akt Signaling Pathway

Abstract

Background: Previous studies have reported that Hizikia fusiforme, an edible brown seaweed, has diverse health-promoting effects; however, evidence for its anti-cancer potential is still lacking. In this study, we examined the effect of ethanol extract of H. fusiforme (EHF) on the proliferation of B16F10 mouse melanoma cells. Methods: Analyses of cell viability and apoptosis were performed to study the actions of EHF on B16F10 cells. Cellular reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were measured using a flow cytometer. Western blot analysis was carried out to measure apoptosis and phosphoinositide 3-kinase (PI3K)/Akt signaling related proteins. Results: EHF treatment significantly decreased B16F10 cell viability, which was associated with induction of apoptosis. EHF activated caspase-8 and caspase-9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and also increased caspase-3 activity, a typical effect caspase, subsequently leading to poly (ADP-ribose) polymerase cleavage. In addition, EHF destroyed the integrity of mitochondria and increased Bax/ Bcl-2 ratio, which contributed to cytosolic release of cytochrome c. EHF further enhanced intracellular levels of ROS and the addition of N-acetyl cysteine (NAC), a ROS inhibitor, significantly diminished EHF-induced mitochondrial dysfunction and growth inhibition. Moreover, EHF inactivated the PI3K/Akt signaling pathway and LY294002, a PI3K/ Akt inhibitor, increased the apoptosis-inducing effect of EHF. However, increased apoptosis and reduced cell viability by simultaneous treatment of EHF and LY294002 were significantly attenuated in the presence of NAC. Conclusion: These results indicate that EHF induces apoptosis through activation of extrinsic and intrinsic apoptotic pathways and ROS-dependent inactivation of PI3K/Akt signaling in B16F10 cells.

Hizikia fusiformis: Pharmacological and Nutritional Properties

“…Several studies have reported that ethanol extracts of H. fusiformis , fucoidan, and alginate isolated from H. fusiformis possess anti-apoptotic effects [ 7 , 10 , 106 ] ( Table 7 ).…”

“…Recent studies have shown that the ethanol extract of H. fusiformis has potential anticancer activity. The mechanism is mediated by activation of the intrinsic and extrinsic apoptotic pathways; thus, ROS-dependent inactivation of PI3K/Akt signaling through apoptosis was induced in B16F10 mouse melanoma cells [ 106 ]. Similar results showed that the ethanol extract of H. fusiformis markedly suppressed the growth of PC3 cells by regulating the ROS-dependent pathway [ 107 ].…”

ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts

“…Coptidis Rhizoma was obtained from the Dong-Eui Korean Hospital of Dong-Eui University (Busan, Republic of Korea) and was refluxed with 1 L of 70% ethanol solution by sonication for 24 h, as previously described [ 34 ]. After filtering, the extract was concentrated with a rotary vacuum evaporator (Buchi Labortechnik, Flawil, Switzerland), followed by freezing-drying, and then stored at −80 °C.…”

Anticancer Activities of Marine-Derived Phenolic Compounds and Their Derivatives

“…On the other side, anticancer activity of marine phenols could be achieved by the suppression of the telomerase expression and activity or by the modulation of the proliferation signal pathways as reported and reviewed by others [40,59]. Numerous research studies have been conducted so far, investigating the anticancer activity of organic or water extracts obtained mostly from macro-and microalgae, sponges and tunicates [60][61][62][63][64][65][66][67][68]. As admonished by Rosa et al, it is necessary to characterize the chemical composition so that the activity can be associated with the presence of a certain metabolite.…”