{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:48:40Z","timestamp":1780487320034,"version":"3.54.1"},"reference-count":29,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2021R1F1A1058698"],"award-info":[{"award-number":["NRF-2021R1F1A1058698"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua Cham. et Schltdl tubers. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrate that ACN inhibited c-Myc expression through CNOT2 and MID1IP1, and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.<\/jats:p>","DOI":"10.3390\/ijms242417589","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T03:59:24Z","timestamp":1702871964000},"page":"17589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Acetylcorynoline Induces Apoptosis and G2\/M Phase Arrest through the c-Myc Signaling Pathway in Colon Cancer Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Ye-Rin","family":"Park","sequence":"first","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University, 24, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-3171","authenticated-orcid":false,"given":"Wona","family":"Jee","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University, 24, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Mi","family":"Park","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University, 24, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok-Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University, 24, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5644-5960","authenticated-orcid":false,"given":"Ji-Hoon","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University, 24, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3919-4597","authenticated-orcid":false,"given":"Hyungsuk","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University, 24, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Department of Korean Rehabilitation Medicine, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan-Il","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University, 24, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Division of Allergy, Immune and Respiratory System, Department of Internal Medicine, College of Korean Medicine, Kyung Hee Medical Center, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4996-9053","authenticated-orcid":false,"given":"Hyeung-Jin","family":"Jang","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University, 24, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Liang, B.J., Pigula, M., Baglo, Y., Najafali, D., Hasan, T., and Huang, H.-C. (2020). Breaking the selectivity-uptake trade-off of photoimmunoconjugates with nanoliposomal irinotecan for synergistic multi-tier cancer targeting. J. Nanobiotechnol., 18.","DOI":"10.1186\/s12951-019-0560-5"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s12011-019-01730-6","article-title":"Selenium Overcomes Doxorubicin Resistance in Their Nano-platforms Against Breast and Colon Cancers","volume":"193","author":"Ahmed","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/ijc.28722","article-title":"Molecular therapy of colorectal cancer: Progress and future directions","volume":"136","author":"Weng","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jung, J.H., Lee, H.-J., Kim, J.-H., Sim, D.Y., Im, E., Kim, S., Chang, S., and Kim, S.-H. (2020). Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2. Cells, 9.","DOI":"10.3390\/cells9040985"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1136\/jcp.2006.038281","article-title":"HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer","volume":"60","author":"Novotny","year":"2007","journal-title":"J. Clin. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nrc3984","article-title":"MYC: Connecting selective transcriptional control to global RNA production","volume":"15","author":"Kress","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6462","DOI":"10.1038\/onc.2008.312","article-title":"Apoptotic signaling by c-MYC","volume":"27","author":"Hoffman","year":"2008","journal-title":"Oncogene"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/MCB.19.1.1","article-title":"c-Myc target genes involved in cell growth, apoptosis, and metabolism","volume":"19","author":"Dang","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.canlet.2017.09.052","article-title":"CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells","volume":"412","author":"Sohn","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lee, J., Jung, J.H., Hwang, J., Park, J.E., Kim, J.-H., Park, W.Y., Suh, J.Y., and Kim, S.-H. (2019). CNOT2 Is Critically Involved in Atorvastatin Induced Apoptotic and Autophagic Cell Death in Non-Small Cell Lung Cancers. Cancers, 11.","DOI":"10.3390\/cancers11101470"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kim, M.J., Sim, D.Y., Lee, H.M., Lee, H.-J., and Kim, S.-H. (2019). Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK\/ACC. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030582"},{"key":"ref_14","first-page":"1599","article-title":"Antitumor lignanamides from the aerial parts of Corydalis saxicola","volume":"23","author":"Zhang","year":"2016","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Qin, F., Chen, Y., Wang, F.-F., Tang, S.-Q., and Fang, Y.-L. (2023). Corydalis saxicola Bunting: A Review of Its Traditional Uses, Phytochemistry, Pharmacology, and Clinical Applications. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021626"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.neuropharm.2013.08.007","article-title":"Acetylcorynoline attenuates dopaminergic neuron degeneration and \u03b1-synuclein aggregation in animal models of Parkinson\u2019s disease","volume":"82","author":"Fu","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_17","first-page":"331","article-title":"Protective action of corynoline, acetylcorynoline and protopine against experimental liver injury in mice","volume":"32","author":"Wei","year":"1997","journal-title":"Yao Xue Xue Bao"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Fu, R.H., Wang, Y.C., Liu, S.P., Chu, C.L., Tsai, R.T., Ho, Y.C., Chang, W.L., Chiu, S.C., Harn, H.J., and Shyu, W.C. (2013). Acetylcorynoline impairs the maturation of mouse bone marrow-derived dendritic cells via suppression of I\u03baB kinase and mitogen-activated protein kinase activities. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058398"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6194","DOI":"10.1038\/onc.2008.297","article-title":"Caspases in apoptosis and beyond","volume":"27","author":"Li","year":"2008","journal-title":"Oncogene"},{"key":"ref_20","first-page":"3976","article-title":"Specific proteolytic cleavage of poly(ADP-ribose) polymerase: An early marker of chemotherapy-induced apoptosis","volume":"53","author":"Kaufmann","year":"1993","journal-title":"Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1080\/15384047.2014.1002698","article-title":"Inauhzin(c) Inactivates c-Myc Independently of p53","volume":"16","author":"Jung","year":"2015","journal-title":"Cancer Biol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1158\/2159-8290.CD-15-0507","article-title":"MYC, Metabolism, and Cancer","volume":"5","author":"Stine","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jung, J.H., Lee, D., Ko, H.M., and Jang, H.-J. (2021). Inhibition of CNOT2 Induces Apoptosis via MID1IP1 in Colorectal Cancer Cells by Activating p53. Biomolecules, 11.","DOI":"10.3390\/biom11101492"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jphs.2021.04.007","article-title":"Momordin Ic induces G0\/1 phase arrest and apoptosis in colon cancer cells by suppressing SENP1\/c-MYC signaling pathway","volume":"146","author":"Xianjun","year":"2021","journal-title":"J. Pharmacol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4660","DOI":"10.1128\/MCB.01174-13","article-title":"Loss of tumor suppressor RPL5\/RPL11 does not induce cell cycle arrest but impedes proliferation due to reduced ribosome content and translation capacity","volume":"33","author":"Teng","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cell.2012.03.003","article-title":"MYC on the Path to Cancer","volume":"149","author":"Dang","year":"2012","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/bjc.2016.46","article-title":"MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours","volume":"114","author":"Green","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102154","DOI":"10.1016\/j.ctrv.2021.102154","article-title":"MYC as a target for cancer treatment","volume":"94","author":"Duffy","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Park, Y.R., and Jee, W. (2023). Viscum album Induces Apoptosis by Regulating STAT3 Signaling Pathway in Breast Cancer Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241511988"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17589\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:40:33Z","timestamp":1760132433000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,18]]},"references-count":29,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242417589"],"URL":"https:\/\/doi.org\/10.3390\/ijms242417589","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,18]]}}}