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Induction of Apoptosis and Inhibition of Cell Migration by Ethyl Alcohol Extract of Hizikia fusiforme in Human Breast cancer Cells

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48 The 49th International Symposium of Korean Society of Life Science

P41

Pro-apoptotic Effects of Ethanol Extract of Hizikia fusiforme

in Human Leukemic U937 Cells

Cheol Park

1

, Cheng-Yun Jin

2

, Min Ho Han

2

, Il-Whan Choi

3

, Taek-Jeong Nam

4

,

Se-Kwon Kim

5

and Yung Hyun Choi

1,2

*

1

Department of Biochemistry, Dongeui University College of Oriental Medicine and 2

Department of Biomaterial Control, Dongeui University Graduate School, Busan 614-052 3

Department of Microbiology, College of Medicine Inje University, Busan 614-735 4

Department of Food and Life Science, 5Department of Chemistry and Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, South Korea

Hizikia fusiforme, well known as Sea weed fusiforme, is reported to possess many pharmacological activities including antioxidant,

antimutagenic and anticoagulant effect. However, the molecular mechanisms of H. fusiforme on biochemical actions in cancer have not been clearly elucidated yet. The purpose of the present study was to examine the effect of the ethanol extract of H. fusiforme (EEHF) on the anti-proliferative effects of human leukemic U937 cells. It was found that EEHF could inhibit the cell proliferation of U937 cells in a concentration-dependent manner, which was associated with apoptotic cell death such as formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase. The induction of apoptotic cell death by EEHF was connected with a down-regulation of anti-apoptotic Bcl-2, Bcl-XL and IAPs expression. MEHC treatment induced the proteolytic

activation of caspase-3, caspase-8 and caspase-9, and a concomitant inhibition of PARP, β-catenin, PLC-γ1 and DFF45/ICAD proteins. Furthermore, caspase-3 specific inhibitor, z-DEVD-fmk, significantly inhibited EEHF-induced apoptosis demonstrating the important role of caspase-3 in the observed cytotoxic effect. Taken together, these findings suggest that EEHF may be a potential chemo-therapeutic agent for the control of human leukemic U937 cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of EEHF. [This work was supported by a grant from Marine Bioprocess Research Center of the Marine Bio 21 Center funded by the Ministry of Land, Transport and Maritime, Republic of Korea.]

Key words: Hizikia fusiforme, U937, apoptosis, Bcl-2, caspase-3

P42

Induction of Apoptosis and Inhibition of Cell Migration by Ethyl Alcohol

Extract of Hizikia fusiforme in Human Breast cancer Cells

Sun Hwa Jung

1

, Cheol Park

1

, Cheng-Yun Jin

2

, Min Ho Han

2

, Il-Whan Choi

3

,

Taek-Jeong Nam

4

, Se-Kwon Kim

5

and Yung Hyun Choi

1,2

*

1

Department of Biomaterial Control, Dongeui University Graduate School and 2

Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052 3

Department of Microbiology, College of Medicine Inje University, Busan 614-735 4

Department of Food and Life Science, 5Department of Chemistry and Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, South Korea

Hizikia fusiforme is a kind of brown edible seaweed that mainly grows in the temperate seaside areas of the northwest Pacific

including Korea, Japan and Chine. Recently, H. fusiforme has been known to exert antioxidant, antimutagenic and anticoagulant activity, however, the molecular mechanisms of H. fusiforme in malignant cells have been poorly studied until now. In this study, we investigated the effects of ethyl alcohol extract of H. fusiforme (EAHF) on the anti-proliferative effects of MDA-MB-231 and MCF-7 human breast cancer cells. EAHF treatment resulted in a concentration-dependent growth inhibition by including apoptosis in MDA-MB-231 cells and G1 phase arrest in MCF-7 cells. In MDA-MB-231 cells, the increase in apoptosis induced by EAHF was correlated with up-regulation of pro-apoptotic Bax and down-regulation of cIAP-2 expression. EAHF treatment induced the proteolytic activation of caspase-3 and caspase-9, and a concomitant inhibition of poly (ADP-ribose) polymerase (PARP), β-catenin, phospholipase (PLC)-γ1 protein and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Furthmore, the EAHF in-hibited cell migration in a concentration- and time-dependent manner of MDA-MB-231 and MCF-7 cells, as evidenced by the results of the wound healing assay. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. fusiforme. [This work was supported by a grant from Marine Bioprocess Research Center of the Marine Bio 21 Center funded by the Ministry of Land, Transport and Maritime, Republic of Korea.]

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