Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways

Abstract

BackgroundFucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in Asian countries, for improving the therapeutic efficacy and safety of cancer treatment. The present study was carried out to investigate the anti-tumor properties of FE in human carcinoma cells and further examine the underlying mechanisms of its activities.Methodology/Principal FindingFE inhibits the growth of MCF-7, MDA-MB-231, HeLa, and HT1080 cells. FE-mediated apoptosis in MCF-7 cancer cells is accompanied by DNA fragmentation, nuclear condensation, and phosphatidylserine exposure. FE induces mitochondrial membrane permeabilization (MMP) through loss of mitochondrial membrane potential (ΔΨm) and regulation of the expression of Bcl-2 family members. Release of apoptosis-inducing factor (AIF) and cytochrome c precedes MMP. AIF release causes DNA fragmentation, the final stage of apoptosis, via a caspase-independent mitochondrial pathway. Additionally, FE was found to induce phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) 1/2, and apoptosis was found to be attenuated by inhibition of JNK. Furthermore, FE-mediated apoptosis was found to involve the generation of reactive oxygen species (ROS), which are responsible for the decrease of ΔΨm and phosphorylation of JNK, p38, and ERK1/2 kinases.Conclusions/SignificanceThese data suggest that FE activates a caspase-independent apoptotic pathway in MCF-7 cancer cells through activation of ROS-mediated MAP kinases and regulation of the Bcl-2 family protein-mediated mitochondrial pathway. They also provide evidence that FE deserves further investigation as a natural anticancer and cancer preventive agent.

The in vitro and in vivo effects of the low molecular weight fucoidan on the bone osteogenic differentiation properties

“…This results agrees with that obtained for LMW fucoidan extracted from pheophicae cell wall increasing cell proliferation of osteoblast cells and improving bioavailability (Changotade et al 2008). Zhang et al (2011) also demonstrated that enzymatically hydrolyzed 500 Da (Kasperk et al 1995). Previous data reported that LMW fucoidan increased the cell proliferation of 7F2 cells, in order to assess whether LMW fucoidan is able to enhance osteoblast differentiation, we measured ALP and osteocalcin as the phenotype marker of the second and third stage, respectively.…”

Antitumor activity of fucoidan against diffuse large B cell lymphoma <italic>in vitro</italic> and <italic>in vivo</italic>

“…The growth inhibition caused by fucoidan occurred in a dose-and time-dependent manner. Our findings were in agreement with studies of other cancer types [19,23]. Previous studies showed that G 0 /G 1 cell cycle arrest occurred in a non-small-cell bronchopulmonary carcinoma line and breast cancer MCF-7 cells [27,28].…”

The curative effect of fucoidan on visceral leishmaniasis is mediated by activation of MAP kinases through specific protein kinase C isoforms

“…[14][15][16] The immunomodulatory effects of fucoidan may be associated with the expression of pro-inflammatory cytokines along with the generation of NO and ROS. 17,18 Our previous study has established fucoidan as a novel antileishmanial agent. 19 The antileishmanial effect of fucoidan was associated with a shift from disease-promoting Th2 to disease-resolving Th1 cytokine response in conjunction with the generation of NO and ROS.…”