Apoptosis and Cell Cycle Arrest in Two Human Breast Cancer Cell Lines by Dieckol Isolated from Ecklonia cava
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Purpose: Dieckol, a phlorotannin compound isolated from Ecklonia cava, has been reported to have antioxidant, antiviral, anti-inflammatory, and anticancer properties. The purpose of this study was to investigate its anticancer effects on human breast cancer cell lines. Methods: In this study, the viability of two human breast cancer cell lines SK-BR-3 and MCF-7 was investigated after dieckol treatment using a WST-1 assay. Apoptosis and cell cycle distribution were assayed via Annexin V-fluorescein isothiocyanate and propidium iodide staining followed by flow cytometric analysis. Immunoblotting analysis was also performed using Bax/Bcl-2 to determine whether the dieckol-induced apoptosis was mediated by the intrinsic apoptotic pathway. Results: In a dose dependent manner, dieckol reduced the number of viable cells and increased the number of apoptotic cells. The effect of dieckol on the cell cycle distribution was analyzed using flow cytometry. Dieckol treatment significantly increased the percentage of MCF-7 and SK-BR-3 in the G2/M phase. Immunoblot analysis revealed that 24 hours of dieckol exposure increased the Bax/Bcl-2 ratio. Conclusion: Dieckol induced cytotoxicity in MCF-7 and SK-BR-3 human breast cancer cells inducing apoptosis and cell cycle arrest. Therefore, it is suggested that dieckol may be a potential therapeutic agent for breast cancer.
Abstract
Purpose: Dieckol, a phlorotannin compound isolated from Ecklonia cava, has been reported to have antioxidant, antiviral, anti-inflammatory, and anticancer properties. The purpose of this study was to investigate its anticancer effects on human breast cancer cell lines. Methods: In this study, the viability of two human breast cancer cell lines SK-BR-3 and MCF-7 was investigated after dieckol treatment using a WST-1 assay. Apoptosis and cell cycle distribution were assayed via Annexin V-fluorescein isothiocyanate and propidium iodide staining followed by flow cytometric analysis. Immunoblotting analysis was also performed using Bax/Bcl-2 to determine whether the dieckol-induced apoptosis was mediated by the intrinsic apoptotic pathway. Results: In a dose dependent manner, dieckol reduced the number of viable cells and increased the number of apoptotic cells. The effect of dieckol on the cell cycle distribution was analyzed using flow cytometry. Dieckol treatment significantly increased the percentage of MCF-7 and SK-BR-3 in the G2/M phase. Immunoblot analysis revealed that 24 hours of dieckol exposure increased the Bax/Bcl-2 ratio. Conclusion: Dieckol induced cytotoxicity in MCF-7 and SK-BR-3 human breast cancer cells inducing apoptosis and cell cycle arrest. Therefore, it is suggested that dieckol may be a potential therapeutic agent for breast cancer.
참고문헌 (30)
- DeSantis C, "Breast cancer statistics, 2013", CA Cancer J Clin, 64, pp.52~62 (2014)
- Lee JH, "The combination of sorafenib and radiation preferentially inhibits breast cancer stem cells by suppressing HIF-1α expression", Oncol Rep, 29, pp.917~924 (2013)
- Perou CM, "Molecular portraits of human breast tumours", Nature, 406, pp.747~752 (2000)
- Sørlie T, "Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications", Proc Natl Acad Sci U S A, 98, pp.10869~10874 (2001)
- Sotiriou C, "Breast cancer classification and prognosis based on gene expression profiles from a population-based study", Proc Natl Acad Sci U S A, 100, pp.10393~10398 (2003)
- Omidvari S, "Very late relapse in breast cancer survivors: a report of 6 cases", Iran J Cancer Prev, 6, pp.113~117 (2013)
- Tew WP, "Breast and ovarian cancer in the older woman", J Clin Oncol, 32, pp.2553~2561 (2014)
- Lemieux J, "Survey about the use of scalp cooling to prevent alopecia during breast cancer chemotherapy treatment in Canada", Can Oncol Nurs J, 24, pp.102~108 (2014)
- Miller RP, "Mechanisms of Cisplatin nephrotoxicity", Toxins (Basel), 2, pp.2490~2518 (2010)
- Bonofiglio D, "Natural products as promising antitumoral agents in breast cancer: mechanisms of action and molecular targets", Mini Rev Med Chem, 16, pp.596~604 (2016)
- Vadodkar AS, "Chemoprevention of breast cancer by dietary compounds", Anticancer Agents Med Chem, 12, pp.1185~1202 (2012)
- Wijesinghe WA, "Exploiting biological activities of brown seaweed Ecklonia cava for potential industrial applications: a review", Int J Food Sci Nutr, 63, pp.225~235 (2012)
- Kim SK, "Effects of Ecklonia cava ethanolic extracts on airway hyperresponsiveness and inflammation in a murine asthma model: role of suppressor of cytokine signaling", Biomed Pharmacother, 62, pp.289~296 (2008)
- Kang HS, "Inhibitory phlorotannins from the edible brown alga Ecklonia stolonifera on total reactive oxygen species (ROS) generation", Arch Pharm Res, 27, pp.194~198 (2004)
- Kim TH, "Antithrombotic and profibrinolytic activities of eckol and dieckol", J Cell Biochem, 113, pp.2877~2883 (2012)
- Ahn JH, "Dieckol, isolated from the edible brown algae Ecklonia cava, induces apoptosis of ovarian cancer cells and inhibits tumor xenograft growth", J Cancer Res Clin Oncol, 141, pp.255~268 (2015)
- Kim EK, "First evidence that Ecklonia cava-derived dieckol attenuates MCF-7 human breast carcinoma cell migration", Mar Drugs, 13, pp.1785~1797 (2015)
- Lee SM, "Value of 18F-FDG PET", CT for early prediction of pathologic response (by residual cancer burden criteria) of locally advanced breast cancer to neoadjuvant chemotherapy, 2014, pp.39, 882~886
- Li Y, "Chemical components and its antioxidant properties in vitro: an edible marine brown alga, Ecklonia cava", Bioorg Med Chem, 17, pp.1963~1973 (2009)
- Heo SJ, "Effect of phlorotannins isolated from Ecklonia cava on melanogenesis and their protective effect against photo-oxidative stress induced by UV-B radiation", Toxicol In Vitro, 23, pp.1123~1130 (2009)
- Nagayama K, "Bactericidal activity of phlorotannins from the brown alga Ecklonia kurome", J Antimicrob Chemother, 50, pp.889~893 (2002)
- 신현철, "An Antioxidative and Antiinflammatory Agent for Potential Treatment of Osteoarthritis from Ecklonia cava", Archives of Pharmacal Research, 29(2), pp.165~171 (2006), 대한약학회
- Joe MJ, "The inhibitory effects of eckol and dieckol from Ecklonia stolonifera on the expression of matrix metalloproteinase-1 in human dermal fibroblasts", Biol Pharm Bull, 29, pp.1735~1739 (2006)
- Elmore S, "Apoptosis: a review of programmed cell death", Toxicol Pathol, 35, pp.495~516 (2007)
- Hengartner MO, "The biochemistry of apoptosis", Nature, 407, pp.770~776 (2000)
- MacLachlan TK, "Cyclins, cyclin-dependent kinases and cdk inhibitors: implications in cell cycle control and cancer", Crit Rev Eukaryot Gene Expr, 5, pp.127~156 (1995)
- Hartwell LH, "Checkpoints: controls that ensure the order of cell cycle events", Science, 246, pp.629~634 (1989)
- Sherr CJ, "Inhibitors of mammalian G1 cyclin-dependent kinases", Genes Dev, 9, pp.1149~1163 (1995)
- Luk SC, "Cell cycle arrest by a natural product via G2", M checkpoint, 2005, pp.2, 64~69
- Hartwell LH, "Cell cycle control and cancer", Science, 266, pp.1821~1828 (1994)
