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Rich66 · 12-02-2009, 11:17 PM

J Agric Food Chem. 2009 Sep 23;57(18):8677-82.
Fucoidan induces apoptosis through activation of caspase-8 on human breast cancer MCF-7 cells.

Yamasaki-Miyamoto Y, Yamasaki M, Tachibana H, Yamada K.
Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan. yumi_mi_1111@yahoo.co.jp
Fucoidan is an active component of seaweed that has been shown to inhibit proliferation and induce apoptotic cell death in several tumor cells. However, the detailed mechanisms underlying this process have not yet been elucidated. In the present report, we investigated the effect of fucoidan on the induction of apoptosis in human breast cancer MCF-7 cells. Our data demonstrated that fucoidan reduced the viable cell number of MCF-7 cells in a dose- and time-dependent manner. In contrast, fucoidan did not affect the viable cell number of normal human mammary epithelial cells. Results from the apoptosis assay demonstrated that fucoidan induced internucleosomal DNA fragmentation, chromatin condensation, activation of caspase-7, -8, and -9, and cleavage of poly(ADP ribose) polymerase. Furthermore, expression of Bid was decreased, whereas truncated Bid was increased by fucoidan treatment. There was also a decline in cytosolic Bax and a striking increase of cytosolic cytochrome c. Caspase-8-specific inhibitor, z-ITED-fmk, canceled the cytotoxicity of fucoidan, activation of caspase-7, -8, and -9, and a series of changes in Bax, Bid, and cytochrome c. However, caspase-9-specific inhibitor exerted a moderate inhibitory effect on the cytotoxicity of fucoidan. These data indicated that fucoidan could induce apoptotic cell death through a caspase-8-dependent pathway in MCF-7 cells.

PMID: 19754176 [PubMed - in process]

Int J Oncol. 2009 Nov;35(5):1183-9.
Fucoidan-Vitamin C complex suppresses tumor invasion through the basement membrane, with scarce injuries to normal or tumor cells, via decreases in oxidative stress and matrix metalloproteinases.

Saitoh Y, Nagai Y, Miwa N.
Cell-Death Control BioTechnology Laboratory, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Hiroshima 727-0023, Japan.
Fucoidan (Fucdn) and vitamin C (VC) were saturatedly dissolved in water and lyophilized and thoroughly ethanol-rinsed until no detection for supernatant vitamin C to form the Fucdn-VC (1:0.23 wt/wt) inclusion body (Fucdn-VC-IB). Fucdn-VC-IB increased not only VC-stabilizing at 37 degrees C, but also hydroxyl-radical scavenging as shown by ESR/spin-trap method, more markedly than a mere mixture of Fucdn:VC (1:0.23 wt/wt). Invasion of human fibrosarcoma cells HT-1080 through the basement membrane was repressed by Fucdn-VC-IB of non-cytotoxic concentrations without significant inhibition to human skin dermal fibroblasts DUMS-16 cells. Fucdn-VC-IB suppressed the invasiveness-related gelatinases MMP-2/9, and diminished reactive oxygen species inside the cytoplasm around the nucleus, in HT-1080 cells as shown by electrophoretic zymography and the redox indicator NBT assay, respectively. Thus Fucdn-VC-IB markedly exhibits antioxidant and MMP-suppressing activities and preferentially inhibited tumor invasion without cytotoxicity to normal cells, and is suggested as a potent tumor-invasion suppressor.

PMID: 19787274 [PubMed - indexed for MEDLINE]

Biol Pharm Bull. 2009 Oct;32(10):1760-4.

Apoptosis inducing activity of fucoidan in HCT-15 colon carcinoma cells.

Hyun JH, Kim SC, Kang JI, Kim MK, Boo HJ, Kwon JM, Koh YS, Hyun JW, Park DB, Yoo ES, Kang HK.
School of Medicine, Institute of Medical Sciences, Jeju National University, South Kore.
The antitumor activity of fucoidan from Fucus vesiculosus was investigated in human colon carcinoma cells. The crude fucoidan, a polysaccharide composed predominantly of sulfated fucose, markedly inhibited the growth of HCT-15 cells (human colon carcinoma cells). After HCT-15 cells were treated with fucoidan, several apoptotic events such as DNA fragmentation, chromatin condensation and increase of the population of sub-G1 hypodiploid cells were observed. In the mechanism of fucoidan-induced apoptosis, we examined changes in Bcl-2 and Bax protein expression levels and activation of caspases. Fucoidan decreased Bcl-2 expression, whereas the expression of Bax was increased in a time-dependent manner compared to the control. In addition, the active forms of caspase-9 and caspase-3 were increased, and the cleavage of poly(ADP-ribose) polymerase (PARP), a vital substrate of effector caspase, was observed. Furthermore, the induction of apoptosis was also accompanied by a strong activation of extracellular signal-regulated kinase (ERK) and p38 kinase and an inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt in a time-dependent manner. These findings provide evidence demonstrating that the pro-apoptotic effect of fucoidan is mediated through the activation of ERK, p38 and the blocking of the PI3K/Akt signal pathway in HCT-15 cells. These data support the hypothesis that fucoidan may have potential in colon cancer treatment.

PMID: 19801840 [PubMed - in process]

Bull Exp Biol Med. 2007 Jun;143(6):730-2.
Antitumor and antimetastatic activity of fucoidan, a sulfated polysaccharide isolated from the Okhotsk Sea Fucus evanescens brown alga.

[Article in English, Russian]
Alekseyenko TV, Zhanayeva SY, Venediktova AA, Zvyagintseva TN, Kuznetsova TA, Besednova NN, Korolenko TA.
Institute of Physiology, Siberian Division of Russian Academy of Medical Sciences, Novosibirsk.
Antitumor and antimetastatic activities of fucoidan, a sulfated polysaccharide isolated from Fucus evanescens (brown alga in Okhotsk sea), was studied in C57Bl/6 mice with transplanted Lewis lung adenocarcinoma. Fucoidan after single and repeated administration in a dose of 10 mg/kg produced moderate antitumor and antimetastatic effects and potentiated the antimetastatic, but not antitumor activities of cyclophosphamide. Fucoidan in a dose of 25 mg/kg potentiated the toxic effect of cyclophosphamide.

PMID: 18239813 [PubMed - indexed for MEDLINE]

12-02-2009, 11:17 PM	#2
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Fucoidan J Agric Food Chem. 2009 Sep 23;57(18):8677-82. Fucoidan induces apoptosis through activation of caspase-8 on human breast cancer MCF-7 cells. Yamasaki-Miyamoto Y, Yamasaki M, Tachibana H, Yamada K. Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan. yumi_mi_1111@yahoo.co.jp Fucoidan is an active component of seaweed that has been shown to inhibit proliferation and induce apoptotic cell death in several tumor cells. However, the detailed mechanisms underlying this process have not yet been elucidated. In the present report, we investigated the effect of fucoidan on the induction of apoptosis in human breast cancer MCF-7 cells. Our data demonstrated that fucoidan reduced the viable cell number of MCF-7 cells in a dose- and time-dependent manner. In contrast, fucoidan did not affect the viable cell number of normal human mammary epithelial cells. Results from the apoptosis assay demonstrated that fucoidan induced internucleosomal DNA fragmentation, chromatin condensation, activation of caspase-7, -8, and -9, and cleavage of poly(ADP ribose) polymerase. Furthermore, expression of Bid was decreased, whereas truncated Bid was increased by fucoidan treatment. There was also a decline in cytosolic Bax and a striking increase of cytosolic cytochrome c. Caspase-8-specific inhibitor, z-ITED-fmk, canceled the cytotoxicity of fucoidan, activation of caspase-7, -8, and -9, and a series of changes in Bax, Bid, and cytochrome c. However, caspase-9-specific inhibitor exerted a moderate inhibitory effect on the cytotoxicity of fucoidan. These data indicated that fucoidan could induce apoptotic cell death through a caspase-8-dependent pathway in MCF-7 cells. PMID: 19754176 [PubMed - in process] Int J Oncol. 2009 Nov;35(5):1183-9. Fucoidan-Vitamin C complex suppresses tumor invasion through the basement membrane, with scarce injuries to normal or tumor cells, via decreases in oxidative stress and matrix metalloproteinases. Saitoh Y, Nagai Y, Miwa N. Cell-Death Control BioTechnology Laboratory, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Hiroshima 727-0023, Japan. Fucoidan (Fucdn) and vitamin C (VC) were saturatedly dissolved in water and lyophilized and thoroughly ethanol-rinsed until no detection for supernatant vitamin C to form the Fucdn-VC (1:0.23 wt/wt) inclusion body (Fucdn-VC-IB). Fucdn-VC-IB increased not only VC-stabilizing at 37 degrees C, but also hydroxyl-radical scavenging as shown by ESR/spin-trap method, more markedly than a mere mixture of Fucdn:VC (1:0.23 wt/wt). Invasion of human fibrosarcoma cells HT-1080 through the basement membrane was repressed by Fucdn-VC-IB of non-cytotoxic concentrations without significant inhibition to human skin dermal fibroblasts DUMS-16 cells. Fucdn-VC-IB suppressed the invasiveness-related gelatinases MMP-2/9, and diminished reactive oxygen species inside the cytoplasm around the nucleus, in HT-1080 cells as shown by electrophoretic zymography and the redox indicator NBT assay, respectively. Thus Fucdn-VC-IB markedly exhibits antioxidant and MMP-suppressing activities and preferentially inhibited tumor invasion without cytotoxicity to normal cells, and is suggested as a potent tumor-invasion suppressor. PMID: 19787274 [PubMed - indexed for MEDLINE] Biol Pharm Bull. 2009 Oct;32(10):1760-4. Apoptosis inducing activity of fucoidan in HCT-15 colon carcinoma cells. Hyun JH, Kim SC, Kang JI, Kim MK, Boo HJ, Kwon JM, Koh YS, Hyun JW, Park DB, Yoo ES, Kang HK. School of Medicine, Institute of Medical Sciences, Jeju National University, South Kore. The antitumor activity of fucoidan from Fucus vesiculosus was investigated in human colon carcinoma cells. The crude fucoidan, a polysaccharide composed predominantly of sulfated fucose, markedly inhibited the growth of HCT-15 cells (human colon carcinoma cells). After HCT-15 cells were treated with fucoidan, several apoptotic events such as DNA fragmentation, chromatin condensation and increase of the population of sub-G1 hypodiploid cells were observed. In the mechanism of fucoidan-induced apoptosis, we examined changes in Bcl-2 and Bax protein expression levels and activation of caspases. Fucoidan decreased Bcl-2 expression, whereas the expression of Bax was increased in a time-dependent manner compared to the control. In addition, the active forms of caspase-9 and caspase-3 were increased, and the cleavage of poly(ADP-ribose) polymerase (PARP), a vital substrate of effector caspase, was observed. Furthermore, the induction of apoptosis was also accompanied by a strong activation of extracellular signal-regulated kinase (ERK) and p38 kinase and an inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt in a time-dependent manner. These findings provide evidence demonstrating that the pro-apoptotic effect of fucoidan is mediated through the activation of ERK, p38 and the blocking of the PI3K/Akt signal pathway in HCT-15 cells. These data support the hypothesis that fucoidan may have potential in colon cancer treatment. PMID: 19801840 [PubMed - in process] Bull Exp Biol Med. 2007 Jun;143(6):730-2. Antitumor and antimetastatic activity of fucoidan, a sulfated polysaccharide isolated from the Okhotsk Sea Fucus evanescens brown alga. [Article in English, Russian] Alekseyenko TV, Zhanayeva SY, Venediktova AA, Zvyagintseva TN, Kuznetsova TA, Besednova NN, Korolenko TA. Institute of Physiology, Siberian Division of Russian Academy of Medical Sciences, Novosibirsk. Antitumor and antimetastatic activities of fucoidan, a sulfated polysaccharide isolated from Fucus evanescens (brown alga in Okhotsk sea), was studied in C57Bl/6 mice with transplanted Lewis lung adenocarcinoma. Fucoidan after single and repeated administration in a dose of 10 mg/kg produced moderate antitumor and antimetastatic effects and potentiated the antimetastatic, but not antitumor activities of cyclophosphamide. Fucoidan in a dose of 25 mg/kg potentiated the toxic effect of cyclophosphamide. PMID: 18239813 [PubMed - indexed for MEDLINE] __________________ Mom's treatment history (link)