<i>Calocedrus formosana</i> Essential Oils Induce ROS-Mediated Autophagy and Apoptosis by Targeting SIRT1 in Colon Cancer Cells
Colorectal cancer is the most common cancer that affects both sexes and has a poor prognosis due to aggressiveness and chemoresistance. Essential oils isolated from <i>Calocedrus formosana</i> (CF-EOs) have been shown to demonstrate anti-termite, antifungal, anti-mosquito, and anti-micro...
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MDPI AG
2024-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/13/3/284 |
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| author | Atikul Islam Yu-Chun Chang Nai-Wen Tsao Sheng-Yang Wang Pin Ju Chueh |
| author_facet | Atikul Islam Yu-Chun Chang Nai-Wen Tsao Sheng-Yang Wang Pin Ju Chueh |
| author_sort | Atikul Islam |
| collection | DOAJ |
| description | Colorectal cancer is the most common cancer that affects both sexes and has a poor prognosis due to aggressiveness and chemoresistance. Essential oils isolated from <i>Calocedrus formosana</i> (CF-EOs) have been shown to demonstrate anti-termite, antifungal, anti-mosquito, and anti-microbial activities. However, the anticancer effects of CF-EOs are not yet fully understood. Therefore, the present study aimed to explore the molecular mechanism underlying CF-EOs-mediated anti-proliferative activity in colon cancer cells. Here, cell impedance measurements showed that CF-EOs inhibit proliferation in colon cancer cells with wild-type or mutant p53. Flow cytometry revealed that CF-EOs at 20, 50 µg/mL significantly induced ROS generation and autophagy in both HCT116 p53-wt and HCT116 p53-null cell lines, whereas pretreatment with the ROS scavenger N-acetyl cysteine (NAC) markedly attenuated these changes. CF-EOs also induced apoptosis at 50 µg/mL in both lines, as determined by flow cytometry. Protein analysis showed that CF-EOs markedly induced apoptosis markers, including Trail, cleaved caspase-3, cleaved caspase-9, and cleaved PARP, as well as autophagy markers, such as the levels of ULK1, Atg5, Atg6, Atg7, and the conversion of LC3-I to LC3-II. CF-EOs were further found to inhibit the activity and expression of the NAD<sup>+</sup>-dependent deacetylase SIRT1 to increase the levels of acetylated p53 (Ac-p53) in p53-wt cells and acetylated c-Myc (Ac-c-Myc) in p53-null cells, ultimately inducing apoptosis in both lines. Interestingly, suppression of SIRT1 by CF-EOs enhanced the acetylation of ULK1, which in turn prompted ROS-dependent autophagy in colon cancer cells. The induction of apoptosis and autophagy by CF-EOs suggests that they may have potential as a promising new approach for treating cancer. Collectively, our results suggest that essential oils isolated from <i>Calocedrus formosana</i> act as a promising anticancer agent against colon cancer cells by targeting SIRT1 to induce ROS-mediated autophagy and apoptosis. |
| first_indexed | 2024-04-24T18:36:35Z |
| format | Article |
| id | doaj.art-5672cbfb097b438ab28940e508137d03 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-04-24T18:36:35Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-5672cbfb097b438ab28940e508137d032024-03-27T13:18:27ZengMDPI AGAntioxidants2076-39212024-02-0113328410.3390/antiox13030284<i>Calocedrus formosana</i> Essential Oils Induce ROS-Mediated Autophagy and Apoptosis by Targeting SIRT1 in Colon Cancer CellsAtikul Islam0Yu-Chun Chang1Nai-Wen Tsao2Sheng-Yang Wang3Pin Ju Chueh4Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, TaiwanInstitute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, TaiwanSpecial Crop and Metabolome Discipline Cluster, Academy Circle Economy, National Chung Hsing University, Taichung City 402202, TaiwanDepartment of Forestry, National Chung Hsing University, Taichung 40402, TaiwanInstitute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, TaiwanColorectal cancer is the most common cancer that affects both sexes and has a poor prognosis due to aggressiveness and chemoresistance. Essential oils isolated from <i>Calocedrus formosana</i> (CF-EOs) have been shown to demonstrate anti-termite, antifungal, anti-mosquito, and anti-microbial activities. However, the anticancer effects of CF-EOs are not yet fully understood. Therefore, the present study aimed to explore the molecular mechanism underlying CF-EOs-mediated anti-proliferative activity in colon cancer cells. Here, cell impedance measurements showed that CF-EOs inhibit proliferation in colon cancer cells with wild-type or mutant p53. Flow cytometry revealed that CF-EOs at 20, 50 µg/mL significantly induced ROS generation and autophagy in both HCT116 p53-wt and HCT116 p53-null cell lines, whereas pretreatment with the ROS scavenger N-acetyl cysteine (NAC) markedly attenuated these changes. CF-EOs also induced apoptosis at 50 µg/mL in both lines, as determined by flow cytometry. Protein analysis showed that CF-EOs markedly induced apoptosis markers, including Trail, cleaved caspase-3, cleaved caspase-9, and cleaved PARP, as well as autophagy markers, such as the levels of ULK1, Atg5, Atg6, Atg7, and the conversion of LC3-I to LC3-II. CF-EOs were further found to inhibit the activity and expression of the NAD<sup>+</sup>-dependent deacetylase SIRT1 to increase the levels of acetylated p53 (Ac-p53) in p53-wt cells and acetylated c-Myc (Ac-c-Myc) in p53-null cells, ultimately inducing apoptosis in both lines. Interestingly, suppression of SIRT1 by CF-EOs enhanced the acetylation of ULK1, which in turn prompted ROS-dependent autophagy in colon cancer cells. The induction of apoptosis and autophagy by CF-EOs suggests that they may have potential as a promising new approach for treating cancer. Collectively, our results suggest that essential oils isolated from <i>Calocedrus formosana</i> act as a promising anticancer agent against colon cancer cells by targeting SIRT1 to induce ROS-mediated autophagy and apoptosis.https://www.mdpi.com/2076-3921/13/3/284colorectal cancer<i>Calocedrus formosana</i>essential oilsreactive oxygen species (ROS)autophagyapoptosis |
| spellingShingle | Atikul Islam Yu-Chun Chang Nai-Wen Tsao Sheng-Yang Wang Pin Ju Chueh <i>Calocedrus formosana</i> Essential Oils Induce ROS-Mediated Autophagy and Apoptosis by Targeting SIRT1 in Colon Cancer Cells Antioxidants colorectal cancer <i>Calocedrus formosana</i> essential oils reactive oxygen species (ROS) autophagy apoptosis |
| title | <i>Calocedrus formosana</i> Essential Oils Induce ROS-Mediated Autophagy and Apoptosis by Targeting SIRT1 in Colon Cancer Cells |
| title_full | <i>Calocedrus formosana</i> Essential Oils Induce ROS-Mediated Autophagy and Apoptosis by Targeting SIRT1 in Colon Cancer Cells |
| title_fullStr | <i>Calocedrus formosana</i> Essential Oils Induce ROS-Mediated Autophagy and Apoptosis by Targeting SIRT1 in Colon Cancer Cells |
| title_full_unstemmed | <i>Calocedrus formosana</i> Essential Oils Induce ROS-Mediated Autophagy and Apoptosis by Targeting SIRT1 in Colon Cancer Cells |
| title_short | <i>Calocedrus formosana</i> Essential Oils Induce ROS-Mediated Autophagy and Apoptosis by Targeting SIRT1 in Colon Cancer Cells |
| title_sort | i calocedrus formosana i essential oils induce ros mediated autophagy and apoptosis by targeting sirt1 in colon cancer cells |
| topic | colorectal cancer <i>Calocedrus formosana</i> essential oils reactive oxygen species (ROS) autophagy apoptosis |
| url | https://www.mdpi.com/2076-3921/13/3/284 |
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