Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells
It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investi...
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MDPI AG
2017-05-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/15/6/154 |
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| author | Hye Young Park Shin-Hyung Park Jin-Woo Jeong Dahye Yoon Min Ho Han Dae-Sung Lee Grace Choi Mi-Jin Yim Jeong Min Lee Do-Hyung Kim Gi-Young Kim Il-Whan Choi Suhkmann Kim Heui-Soo Kim Hee-Jae Cha Yung Hyun Choi |
| author_facet | Hye Young Park Shin-Hyung Park Jin-Woo Jeong Dahye Yoon Min Ho Han Dae-Sung Lee Grace Choi Mi-Jin Yim Jeong Min Lee Do-Hyung Kim Gi-Young Kim Il-Whan Choi Suhkmann Kim Heui-Soo Kim Hee-Jae Cha Yung Hyun Choi |
| author_sort | Hye Young Park |
| collection | DOAJ |
| description | It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investigated the anticancer effect of fucoidan on two p53 isogenic HCT116 (p53+/+ and p53−/−) cell lines. Our results showed that inhibition of cell viability, induction of apoptosis and DNA damage by treatment with fucoidan were similar in two cell lines. Flow cytometric analysis revealed that fucoidan resulted in G1 arrest in the cell cycle progression, which correlated with the inhibition of phosphorylation of retinoblastoma protein (pRB) and concomitant association of pRB with the transcription factor E2Fs. Furthermore, treatment with fucoidan obviously upregulated the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21WAF1/CIP1 and p27KIP1, which was paralleled by an enhanced binding with CDK2 and CDK4. These events also commonly occurred in both cell lines, suggesting that fucoidan triggered G1 arrest and apoptosis in HCT116 cells by a p53-independent mechanism. Thus, given that most tumors exhibit functional p53 inactivation, fucoidan could be a possible therapeutic option for cancer treatment regardless of the p53 status. |
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| language | English |
| last_indexed | 2024-04-11T22:45:10Z |
| publishDate | 2017-05-01 |
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| series | Marine Drugs |
| spelling | doaj.art-5528bc32066b4b0e82ee30a8690143b32022-12-22T03:58:48ZengMDPI AGMarine Drugs1660-33972017-05-0115615410.3390/md15060154md15060154Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma CellsHye Young Park0Shin-Hyung Park1Jin-Woo Jeong2Dahye Yoon3Min Ho Han4Dae-Sung Lee5Grace Choi6Mi-Jin Yim7Jeong Min Lee8Do-Hyung Kim9Gi-Young Kim10Il-Whan Choi11Suhkmann Kim12Heui-Soo Kim13Hee-Jae Cha14Yung Hyun Choi15Department of Biochemistry, Dong-Eui University College of Korean Medicine, Busan 47227, KoreaDepartment of Pathology, Dong-Eui University College of Korean Medicine, Busan 47227, KoreaAnti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 47227, KoreaDepartment of Chemistry, College of Natural Sciences, Pusan National University, Busan 46241, KoreaDepartment of Applied Research, National Marine Biodiversity Institute of Korea, Seocheon 33662, KoreaDepartment of Applied Research, National Marine Biodiversity Institute of Korea, Seocheon 33662, KoreaDepartment of Applied Research, National Marine Biodiversity Institute of Korea, Seocheon 33662, KoreaDepartment of Applied Research, National Marine Biodiversity Institute of Korea, Seocheon 33662, KoreaDepartment of Applied Research, National Marine Biodiversity Institute of Korea, Seocheon 33662, KoreaDepartment of Aquatic Life Medicine, Pukyong National University, Busan, 48513, KoreaLaboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 63243, KoreaDepartment of Microbiology, College of Medicine, Inje University, Busan 47392, KoreaDepartment of Chemistry, College of Natural Sciences, Pusan National University, Busan 46241, KoreaDepartment of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, KoreaDepartments of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, KoreaDepartment of Biochemistry, Dong-Eui University College of Korean Medicine, Busan 47227, KoreaIt is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investigated the anticancer effect of fucoidan on two p53 isogenic HCT116 (p53+/+ and p53−/−) cell lines. Our results showed that inhibition of cell viability, induction of apoptosis and DNA damage by treatment with fucoidan were similar in two cell lines. Flow cytometric analysis revealed that fucoidan resulted in G1 arrest in the cell cycle progression, which correlated with the inhibition of phosphorylation of retinoblastoma protein (pRB) and concomitant association of pRB with the transcription factor E2Fs. Furthermore, treatment with fucoidan obviously upregulated the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21WAF1/CIP1 and p27KIP1, which was paralleled by an enhanced binding with CDK2 and CDK4. These events also commonly occurred in both cell lines, suggesting that fucoidan triggered G1 arrest and apoptosis in HCT116 cells by a p53-independent mechanism. Thus, given that most tumors exhibit functional p53 inactivation, fucoidan could be a possible therapeutic option for cancer treatment regardless of the p53 status.http://www.mdpi.com/1660-3397/15/6/154fucoidancolorectal carcinomap53G1 arrestapoptosis |
| spellingShingle | Hye Young Park Shin-Hyung Park Jin-Woo Jeong Dahye Yoon Min Ho Han Dae-Sung Lee Grace Choi Mi-Jin Yim Jeong Min Lee Do-Hyung Kim Gi-Young Kim Il-Whan Choi Suhkmann Kim Heui-Soo Kim Hee-Jae Cha Yung Hyun Choi Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells Marine Drugs fucoidan colorectal carcinoma p53 G1 arrest apoptosis |
| title | Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells |
| title_full | Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells |
| title_fullStr | Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells |
| title_full_unstemmed | Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells |
| title_short | Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells |
| title_sort | induction of p53 independent apoptosis and g1 cell cycle arrest by fucoidan in hct116 human colorectal carcinoma cells |
| topic | fucoidan colorectal carcinoma p53 G1 arrest apoptosis |
| url | http://www.mdpi.com/1660-3397/15/6/154 |
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