Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis
β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an anti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP exerted an anti-cancer effect against the CRC...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/24/13514 |
| _version_ | 1797503830552739840 |
|---|---|
| author | Jin-Hee Kwon Na-Gyeong Lee A-Ram Kang Jie-Young Song Sang-Gu Hwang Hong-Duck Um Joon Kim Jong Kuk Park |
| author_facet | Jin-Hee Kwon Na-Gyeong Lee A-Ram Kang Jie-Young Song Sang-Gu Hwang Hong-Duck Um Joon Kim Jong Kuk Park |
| author_sort | Jin-Hee Kwon |
| collection | DOAJ |
| description | β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an anti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP exerted an anti-cancer effect against the CRC cell lines HCT116, DLD-1, SW480, and COLO320DM, with IC50 values of 7.88 nM, 8.22 nM, 9.84 nM, and 7.757 nM, respectively, for the induction of DNA damage. Clonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either treatment alone, suggesting that APP sensitized CRC cells to IR. Annexin V–propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in the in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells. |
| first_indexed | 2024-03-10T03:55:57Z |
| format | Article |
| id | doaj.art-d298653bb5f7430fb07c7de05d8a650a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:55:57Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d298653bb5f7430fb07c7de05d8a650a2023-11-23T08:47:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241351410.3390/ijms222413514Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and ApoptosisJin-Hee Kwon0Na-Gyeong Lee1A-Ram Kang2Jie-Young Song3Sang-Gu Hwang4Hong-Duck Um5Joon Kim6Jong Kuk Park7Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivision of Life Sciences, Korea University, Seoul 02841, KoreaDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Koreaβ-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an anti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP exerted an anti-cancer effect against the CRC cell lines HCT116, DLD-1, SW480, and COLO320DM, with IC50 values of 7.88 nM, 8.22 nM, 9.84 nM, and 7.757 nM, respectively, for the induction of DNA damage. Clonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either treatment alone, suggesting that APP sensitized CRC cells to IR. Annexin V–propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in the in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.https://www.mdpi.com/1422-0067/22/24/13514β-apopicropodophyllinradiosensitizertopoisomerase inhibitorROSapoptosiscolorectal cancer |
| spellingShingle | Jin-Hee Kwon Na-Gyeong Lee A-Ram Kang Jie-Young Song Sang-Gu Hwang Hong-Duck Um Joon Kim Jong Kuk Park Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis International Journal of Molecular Sciences β-apopicropodophyllin radiosensitizer topoisomerase inhibitor ROS apoptosis colorectal cancer |
| title | Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis |
| title_full | Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis |
| title_fullStr | Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis |
| title_full_unstemmed | Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis |
| title_short | Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis |
| title_sort | radiosensitizer effect of β apopicropodophyllin against colorectal cancer via induction of reactive oxygen species and apoptosis |
| topic | β-apopicropodophyllin radiosensitizer topoisomerase inhibitor ROS apoptosis colorectal cancer |
| url | https://www.mdpi.com/1422-0067/22/24/13514 |
| work_keys_str_mv | AT jinheekwon radiosensitizereffectofbapopicropodophyllinagainstcolorectalcancerviainductionofreactiveoxygenspeciesandapoptosis AT nagyeonglee radiosensitizereffectofbapopicropodophyllinagainstcolorectalcancerviainductionofreactiveoxygenspeciesandapoptosis AT aramkang radiosensitizereffectofbapopicropodophyllinagainstcolorectalcancerviainductionofreactiveoxygenspeciesandapoptosis AT jieyoungsong radiosensitizereffectofbapopicropodophyllinagainstcolorectalcancerviainductionofreactiveoxygenspeciesandapoptosis AT sangguhwang radiosensitizereffectofbapopicropodophyllinagainstcolorectalcancerviainductionofreactiveoxygenspeciesandapoptosis AT hongduckum radiosensitizereffectofbapopicropodophyllinagainstcolorectalcancerviainductionofreactiveoxygenspeciesandapoptosis AT joonkim radiosensitizereffectofbapopicropodophyllinagainstcolorectalcancerviainductionofreactiveoxygenspeciesandapoptosis AT jongkukpark radiosensitizereffectofbapopicropodophyllinagainstcolorectalcancerviainductionofreactiveoxygenspeciesandapoptosis |