https://doi.org/10.4081/ejh.2023.3697
Crocin exerts anti-tumor effect in colon cancer cells via repressing the JAK pathway
Submitted: 27 February 2023
Accepted: 10 August 2023
Published: 12 September 2023
Accepted: 10 August 2023
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Crocin has been reported to have therapeutic effects on multiple cancers including colon cancer, but its specific mechanism is still ambiguous and needs to be further explored. Human colorectal adenocarcinoma cells (HCT-116) and human normal colonic epithelial cells (CCD841) were first treated with increasing concentrations of crocin. Subsequently, with 150 and 200 μM of crocin, the cell vitality was examined by cell counting kit 8. Cell apoptosis and proliferation were tested by TUNEL staining and colony formation assay, respectively. The expression of Ki-67 was assessed by immunofluorescence. Enzyme-linked immunosorbent assay was used to evaluate the level of inflammation- and oxidative-related factors. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were examined by flow cytometer. Janus kinase (JAK), signal transducer and activator of transcription 3 (STAT3), and extracellular regulated protein kinases (ERK) in HCT-116 cells were tested by Western blot. Different concentrations of crocin barely affected the CCD841 cell vitality, while crocin restrained the HCT-116 cells vitality, proliferation and the expression of Ki-67, while inducing apoptosis in a concentration-dependent manner. Moreover, the contents of inflammation- and oxidative-related factors in HCT-116 cells were largely blunted by crocin that enhanced ROS and restrained the MMP and suppressed p-JAK2/JAK2, p-STAT3/STAT3, and p-ERK/ERK expression in HCT-116 cells. Crocin induced apoptosis and restored mitochondrial function in HCT-116 cells via repressing the JAK pathway. If the threptic effect works in patients, it could herald a new, effective treatment for colon cancer, improving the patients’ prognosis and quality of life.
Coskun AK, Harlak A. The relation between anastomotic dehiscence following colon cancer surgery and risk factors. Int J Colorectal Dis 2016;31:1489-90.
DOI: https://doi.org/10.1007/s00384-016-2552-3
Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin 2023;73:233-54.
DOI: https://doi.org/10.3322/caac.21772
Feng Y, Dai X, Li X, Wang H, Liu J, Zhang J, et al. EGF signalling pathway regulates colon cancer stem cell proliferation and apoptosis. Cell Prolif 2012;45:413-9.
DOI: https://doi.org/10.1111/j.1365-2184.2012.00837.x
Edwards BK, Ward E, Kohler BA, Eheman C, Zauber AG, Anderson RN, et al. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer 2010;116:544-73.
DOI: https://doi.org/10.1002/cncr.24760
Franko J, Shi Q, Goldman CD, Pockaj BA, Nelson GD, Goldberg RM, et al. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol 2012;30:263-7.
DOI: https://doi.org/10.1200/JCO.2011.37.1039
Hodgkinson N, Kruger CA, Abrahamse H. Targeted photodynamic therapy as potential treatment modality for the eradication of colon cancer and colon cancer stem cells. Tumour Biol 2017;39:1010428317734691.
DOI: https://doi.org/10.1177/1010428317734691
Wu Y, Pan RR, Geng P. [The effect of crocin against hypoxia damage of myocardial cell and its mechanism].[Article in Chinese]. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2010;26:453-7.
He SY, Qian ZY, Tang FT, Wen N, Xu GL, Sheng L. Effect of crocin on experimental atherosclerosis in quails and its mechanisms. Life Sci 2005;77:907-21.
DOI: https://doi.org/10.1016/j.lfs.2005.02.006
Asdaq SM, Inamdar MN. Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats. Appl Biochem Biotechnol 2010;162:358-72.
DOI: https://doi.org/10.1007/s12010-009-8740-7
Yin Q, Xiong H. Chemotherapy-induced nephrotoxicity was improved by crocin in mouse model. Eur J Histochem 2022;66:3541.
DOI: https://doi.org/10.4081/ejh.2022.3541
Shariat Razavi SM, Mahmoudzadeh Vaziri R, Karimi G, Arabzadeh S, Keyvani V, Behravan J, et al. Crocin increases gastric cancer cells' sensitivity to doxorubicin. Asian Pac J Cancer Prev 2020;21:1959-67.
DOI: https://doi.org/10.31557/APJCP.2020.21.7.1959
Veisi A, Akbari G, Mard SA, Badfar G, Zarezade V, Mirshekar MA. Role of crocin in several cancer cell lines: An updated review. Iran J Basic Med Sci 2020;23:3-12.
Aung HH, Wang CZ, Ni M, Fishbein A, Mehendale SR, Xie JT, et al. Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol 2007;29:175-80.
García-Olmo DC, Riese HH, Escribano J, Ontañón J, Fernandez JA, Atiénzar M, et al. Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): an experimental study in the rat. Nutr Cancer 1999;35:120-6.
DOI: https://doi.org/10.1207/S15327914NC352_4
Rastgoo M, Hosseinzadeh H, Alavizadeh H, Abbasi A, Ayati Z, Jaafari MR. Antitumor activity of PEGylated nanoliposomes containing crocin in mice bearing C26 colon carcinoma. Planta Med 2013;79:447-51.
DOI: https://doi.org/10.1055/s-0032-1328363
Wang J, Ke Y, Shu T. Crocin has pharmacological effects against the pathological behavior of colon cancer cells by interacting with the STAT3 signaling pathway. Exp Ther Med 2020;19:1297-303.
DOI: https://doi.org/10.3892/etm.2019.8329
Bakshi HA, Quinn GA, Nasef MM, Mishra V, Aljabali AAA, El-Tanani M, et al. Crocin inhibits angiogenesis and metastasis in colon cancer via TNF-α/NF-kB/VEGF pathways. Cells 2022;11:1502.
DOI: https://doi.org/10.3390/cells11091502
Wang W, Li Y, Chen Y, Chen H, Zhu P, Xu M, et al. Ethanolic extract of traditional Chinese medicine (TCM) gamboge inhibits colon cancer via the Wnt/beta-catenin signaling pathway in an orthotopic mouse model. Anticancer Res 2018;38:1917-25.
DOI: https://doi.org/10.21873/anticanres.12429
Sui H, Zhu HR, Wu J, Nikitin AY, Cai JF, Fan ZZ, et al. Effects of Jianpi Jiedu recipe on reversion of P-glycoprotein-mediated multidrug resistance through COX-2 pathway in colorectal cancer. Chin J Integr Med 2014;20:610-7.
DOI: https://doi.org/10.1007/s11655-013-1452-4
Liu X, Ji Q, Deng W, Chai N, Feng Y, Zhou L, et al. JianPi JieDu recipe inhibits epithelial-to-mesenchymal transition in colorectal cancer through TGF-β/Smad mediated snail/E-cadherin expression. Biomed Res Int 2017;2017:2613198.
DOI: https://doi.org/10.1155/2017/2613198
Fei B, Dai W, Zhao S. Efficacy, safety, and cost of therapy of the traditional Chinese medicine, catalpol, in patients following surgical resection for locally advanced colon cancer. Med Sci Monit 2018;24:3184-92.
DOI: https://doi.org/10.12659/MSM.907569
Zhou LY, Shan ZZ, You JL. Clinical observation on treatment of colonic cancer with combined treatment of chemotherapy and Chinese herbal medicine. Chin J Integr Med 2009;15:107-11.
DOI: https://doi.org/10.1007/s11655-009-0107-y
Ni H, Han Y, Jin X. Celastrol inhibits colon cancer cell proliferation by downregulating miR-21 and PI3K/AKT/GSK-3β pathway. Int J Clin Exp Pathol 2019;12:808-16.
Wang G, Zhang B, Wang Y, Han S, Wang C. Crocin promotes apoptosis of human skin cancer cells by inhibiting the JAK/STAT pathway. Exp Ther Med 2018;16:5079-84.
DOI: https://doi.org/10.3892/etm.2018.6865
Mousavi SH, Moallem SA, Mehri S, Shahsavand S, Nassirli H, Malaekeh-Nikouei B. Improvement of cytotoxic and apoptogenic properties of crocin in cancer cell lines by its nanoliposomal form. Pharm Biol 2011;49:1039-45.
DOI: https://doi.org/10.3109/13880209.2011.563315
Sun J, Xu XM, Ni CZ, Zhang H, Li XY, Zhang CL, et al. Crocin inhibits proliferation and nucleic acid synthesis and induces apoptosis in the human tongue squamous cell carcinoma cell line Tca8113. Asian Pac J Cancer Prev 2011;12:2679-83.
Magesh V, Singh JP, Selvendiran K, Ekambaram G, Sakthisekaran D. Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies. Mol Cell Biochem 2006;287:127-35.
DOI: https://doi.org/10.1007/s11010-005-9088-0
Zhang L, Hu Y, Xi N, Song J, Huang W, Song S, et al. Partial Oxygen pressure affects the expression of prognostic biomarkers HIF-1 alpha, Ki67, and CK20 in the microenvironment of colorectal cancer tissue. Oxid Med Cell Longev 2016;2016:1204715.
DOI: https://doi.org/10.1155/2016/1204715
Scarlett JL, Sheard PW, Hughes G, Ledgerwood EC, Ku HH, Murphy MP. Changes in mitochondrial membrane potential during staurosporine-induced apoptosis in Jurkat cells. FEBS Lett 2000;475:267-72.
DOI: https://doi.org/10.1016/S0014-5793(00)01681-1
Qin L, Yao ZQ, Chang Q, Zhao YL, Liu NN, Zhu XS, et al. Swimming attenuates inflammation, oxidative stress, and apoptosis in a rat model of dextran sulfate sodium-induced chronic colitis. Oncotarget 2017;8:7391-404.
DOI: https://doi.org/10.18632/oncotarget.14080
Fenton JI, Hursting SD, Perkins SN, Hord NG. Leptin induces an Apc genotype-associated colon epithelial cell chemokine production pattern associated with macrophage chemotaxis and activation. Carcinogenesis 2007;28:455-64.
DOI: https://doi.org/10.1093/carcin/bgl137
Yoshidome H, Kohno H, Shida T, Kimura F, Shimizu H, Ohtsuka M, et al. Significance of monocyte chemoattractant protein-1 in angiogenesis and survival in colorectal liver metastases. Int J Oncol 2009;34:923-30.
DOI: https://doi.org/10.3892/ijo_00000218
Kollmar O, Junker B, Rupertus K, Menger MD, Schilling MK. Studies on MIP-2 and CXCR2 expression in a mouse model of extrahepatic colorectal metastasis. Eur J Surg Oncol 2007;33:803-11.
DOI: https://doi.org/10.1016/j.ejso.2007.01.012
Kusaba T, Nakayama T, Yamazumi K, Yakata Y, Yoshizaki A, Nagayasu T, et al. Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma;correlation with clinicopathological factors. J Clin Pathol 2005;58:833-8.
DOI: https://doi.org/10.1136/jcp.2004.023416
Gao B, Shen X, Kunos G, Meng Q, Goldberg ID, Rosen EM, et al. Constitutive activation of JAK-STAT3 signaling by BRCA1 in human prostate cancer cells. FEBS Lett 2001;488:179-84.
DOI: https://doi.org/10.1016/S0014-5793(00)02430-3
Khanna P, Lee JS, Sereemaspun A, Lee H, Baeg GH. GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling. Sci Rep 2018;8:9511.
DOI: https://doi.org/10.1038/s41598-018-27864-6
Li T, Zhao J, Ge J, Yang J, Song X, Wang C, et al. Particulate matter facilitates C6 glioma cells activation and the release of inflammatory factors through MAPK and JAK2/STAT3 pathways. Neurochem Res 2016;41:1969-81.
DOI: https://doi.org/10.1007/s11064-016-1908-y
Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 2007;26:3291-310.
DOI: https://doi.org/10.1038/sj.onc.1210422
How to Cite
Yang, H., Zhang, Y., Zhang, D., Qian, L., Yang, T., & Wu, X. (2023). Crocin exerts anti-tumor effect in colon cancer cells <em>via</em> repressing the JAK pathway . European Journal of Histochemistry, 67(3). https://doi.org/10.4081/ejh.2023.3697
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