Cytotoxic activity of the twigs of Cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cells
Abstract Background Because twigs of Cinnamomum cassia (TC) have been reported to exert anti-cancer activity, the mechanistic study for TC’s anti-cancer activity is required. Thus, we elucidated the potential molecular mechanism of TC’s anti-proliferative effect and the induction of apoptosis in hum...
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | BMC Complementary and Alternative Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12906-018-2096-x |
| _version_ | 1828404404331479040 |
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| author | Gwang Hun Park Hun Min Song Su Bin Park Ho-Jun Son Yurry Um Hyun-Seok Kim Jin Boo Jeong |
| author_facet | Gwang Hun Park Hun Min Song Su Bin Park Ho-Jun Son Yurry Um Hyun-Seok Kim Jin Boo Jeong |
| author_sort | Gwang Hun Park |
| collection | DOAJ |
| description | Abstract Background Because twigs of Cinnamomum cassia (TC) have been reported to exert anti-cancer activity, the mechanistic study for TC’s anti-cancer activity is required. Thus, we elucidated the potential molecular mechanism of TC’s anti-proliferative effect and the induction of apoptosis in human colorectal cancer cells. Methods How water extracts form TC (TC-HW) was used in this study. Anti-cell proliferative effect of TC-HW was evaluated by MTT assay. The change of protein or mRNA level by TC-HW was evaluated by Western blot and RT-RCR, respectively. The promoter construct for ATF3, NF-κB, TOP-FLASH or FOP-FLASH was used for the investigation of the transcriptional activity for ATF3, NF-κB or Wnt. siRNA for ATF3 or p65 was used for the knockdown of ATF3 and p65. Results TC-HW reduced the cell viability in human colorectal cancer cells. TC-HW decreased cyclin D1 protein level through cyclin D1 degradation via GSK3β-dependent threonine-286 (T286) phosphorylation of cyclin D1, indicating that cyclin D1 degradation may contribute to TC-HW-mediated decrease of cyclin D1 protein level. TC-HW downregulated the expression of cyclin D1 mRNA level and inhibited Wnt activation through the downregulation of β-catenin and TCF4 expression, indicating that inhibition of cyclin D1 transcription may also result in TC-HW-mediated decrease of cyclin D1 protein level. In addition, TC-HW was observed to induce apoptosis through ROS-dependent DNA damage. TC-HW-induced ROS increased NF-κB and ATF3 activation, and inhibition of NF-κB and ATF3 activation attenuated TC-HW-mediated apoptosis. Conclusions Our results suggest that TC-HW may suppress cell proliferation through the downregulation of cyclin D1 via proteasomal degradation and transcriptional inhibition, and may induce apoptosis through ROS-dependent NF-κB and ATF3 activation. These effects of TC-HW may contribute to the reduction of cell viability in human colorectal cancer cells. From these findings, TC-HW has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. |
| first_indexed | 2024-12-10T10:35:46Z |
| format | Article |
| id | doaj.art-2aab6c140d44408398f07e1a6c25d7cf |
| institution | Directory Open Access Journal |
| issn | 1472-6882 |
| language | English |
| last_indexed | 2024-12-10T10:35:46Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary and Alternative Medicine |
| spelling | doaj.art-2aab6c140d44408398f07e1a6c25d7cf2022-12-22T01:52:26ZengBMCBMC Complementary and Alternative Medicine1472-68822018-01-0118111310.1186/s12906-018-2096-xCytotoxic activity of the twigs of Cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cellsGwang Hun Park0Hun Min Song1Su Bin Park2Ho-Jun Son3Yurry Um4Hyun-Seok Kim5Jin Boo Jeong6Forest Medicinal Resources Research Center, National Institute of Forest ScienceDepartment of Medicinal Plant Resources, Andong National UniversityDepartment of Medicinal Plant Resources, Andong National UniversityForest Medicinal Resources Research Center, National Institute of Forest ScienceForest Medicinal Resources Research Center, National Institute of Forest ScienceDepartment of Food Science & Biotechnology, Kyonggi UniversityDepartment of Medicinal Plant Resources, Andong National UniversityAbstract Background Because twigs of Cinnamomum cassia (TC) have been reported to exert anti-cancer activity, the mechanistic study for TC’s anti-cancer activity is required. Thus, we elucidated the potential molecular mechanism of TC’s anti-proliferative effect and the induction of apoptosis in human colorectal cancer cells. Methods How water extracts form TC (TC-HW) was used in this study. Anti-cell proliferative effect of TC-HW was evaluated by MTT assay. The change of protein or mRNA level by TC-HW was evaluated by Western blot and RT-RCR, respectively. The promoter construct for ATF3, NF-κB, TOP-FLASH or FOP-FLASH was used for the investigation of the transcriptional activity for ATF3, NF-κB or Wnt. siRNA for ATF3 or p65 was used for the knockdown of ATF3 and p65. Results TC-HW reduced the cell viability in human colorectal cancer cells. TC-HW decreased cyclin D1 protein level through cyclin D1 degradation via GSK3β-dependent threonine-286 (T286) phosphorylation of cyclin D1, indicating that cyclin D1 degradation may contribute to TC-HW-mediated decrease of cyclin D1 protein level. TC-HW downregulated the expression of cyclin D1 mRNA level and inhibited Wnt activation through the downregulation of β-catenin and TCF4 expression, indicating that inhibition of cyclin D1 transcription may also result in TC-HW-mediated decrease of cyclin D1 protein level. In addition, TC-HW was observed to induce apoptosis through ROS-dependent DNA damage. TC-HW-induced ROS increased NF-κB and ATF3 activation, and inhibition of NF-κB and ATF3 activation attenuated TC-HW-mediated apoptosis. Conclusions Our results suggest that TC-HW may suppress cell proliferation through the downregulation of cyclin D1 via proteasomal degradation and transcriptional inhibition, and may induce apoptosis through ROS-dependent NF-κB and ATF3 activation. These effects of TC-HW may contribute to the reduction of cell viability in human colorectal cancer cells. From these findings, TC-HW has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.http://link.springer.com/article/10.1186/s12906-018-2096-xAnticancerATF3Cinnamomum cassiaCyclin D1;.Human colorectal cancerNF-κBROS |
| spellingShingle | Gwang Hun Park Hun Min Song Su Bin Park Ho-Jun Son Yurry Um Hyun-Seok Kim Jin Boo Jeong Cytotoxic activity of the twigs of Cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cells BMC Complementary and Alternative Medicine Anticancer ATF3 Cinnamomum cassia Cyclin D1;.Human colorectal cancer NF-κB ROS |
| title | Cytotoxic activity of the twigs of Cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cells |
| title_full | Cytotoxic activity of the twigs of Cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cells |
| title_fullStr | Cytotoxic activity of the twigs of Cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cells |
| title_full_unstemmed | Cytotoxic activity of the twigs of Cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cells |
| title_short | Cytotoxic activity of the twigs of Cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cells |
| title_sort | cytotoxic activity of the twigs of cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cells |
| topic | Anticancer ATF3 Cinnamomum cassia Cyclin D1;.Human colorectal cancer NF-κB ROS |
| url | http://link.springer.com/article/10.1186/s12906-018-2096-x |
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