Article Sidebar
Main Article Content
Matrine Alleviates Oxidative Stress and Inflammation in Colon Cancer by Activating the Nrf2 Pathway
Main Article Content
Abstract
Background/Aims: Oxidative stress (OS) and inflammation are pivotal for colon cancer (CC) development, which can be regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Matrine (MAT) can treat disorders by modulating OS and inflammation with the Nrf2 pathway. This study aimed to investigate the effects of MAT in CC.
Materials and Methods: Mice pretreated with MAT were injected with 1,2-dimethylhydrazine (DMH) to induce CC. Then, colon tissue pathology was examined, and B cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax) and antigen identified by monoclonal antibody Ki 67 (Ki-67) expressions in colon tissues were quantified. Moreover, HT-29 cells were treated with MAT and transfected with si-Nrf2 to fur-ther investigate the mechanisms of MAT on CC. Following treatment with MAT, the viability and apoptosis of HT-29 cells were detected. Furthermore, OS- and inflammation-related factors, as well as Nrf2 pathway-related expressions, were measured both in vivo and in vitro.
Results: Matrine treatment alleviated DMH-induced epithelial structural changes, increased Bcl2 and Ki-67 expressions, but decreased Bax expression in the colon. In vitro, MAT inhibited viability but induced apoptosis in HT-29 cells. Both in vivo and in vitro results revealed that MAT alleviated OS and inflammation, increased Nrf2, NAD(P)H quinone dehydrogenase 1, and heme oxygenase-1 expressions, but reduced kelch-like ECH-associated protein 1 expression in CC models. However, the effects of MAT on CC were reversed by Nrf2 knockdown.
Conclusion: Matrine may alleviate OS and inflammation in CC by activating the Nrf2 pathway, suggesting that MAT may be a promisingstrategy in CC treatment.
Cite this article as: Dong Y, Shang T. Matrine Alleviates Oxidative Stress and Inflammation in Colon Cancer by Activating the Nrf2 Pathway. Turk J Gastroenterol. Published online January 27, 2025. doi 10.5152/tjg.2025.24438
Article Details
References
1. Benson AB, Venook AP, Al-Hawary MM, et al. Colon Cancer. version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021;19(3):329-359.
2. Chen Y, Ling C, Xu Y, Liu J, Tang W. Evaluation of diagnostic and prognostic value of hsa_circ_0084927 and analysis of associated ceRNA network in colorectal cancer. Int J Gen Med. 2022;15:4357-4377. [CrossRef]
3. Lee M, Yang C, Song G, Lim W. Eupatilin impacts on the progression of colon cancer by mitochondria dysfunction and oxidative stress. Antioxidants (Basel, Switzerland). 2021;10(6):957. [CrossRef]
4. Roessner A, Kuester D, Malfertheiner P, Schneider-Stock R. Oxidative stress in ulcerative colitis-associated carcinogenesis. Pathol Res Pract. 2008;204(7):511-524. [CrossRef]
5. Chang Y, Li F, Wang Z, et al. Oxidative balance score: a potential tool for reducing the risk of colorectal cancer and its subsites incidences. Front Endocrinol (Lausanne). 2024;15:1397512. [CrossRef]
6. Li X, Tang Z, Wen L, Jiang C, Feng Q. Matrine: a review of its pharmacology, pharmacokinetics, toxicity, clinical application and preparation researches. J Ethnopharmacol. 2021;269:113682. [CrossRef]
7. Du Q, Lin Y, Ding C, Wu L, Xu Y, Feng Q. Pharmacological activity of Matrine in inhibiting colon cancer cells VM formation, proliferation, and invasion by downregulating Claudin-9 mediated EMT process and MAPK signaling pathway. Drug Des Devel Ther. 2023;17:2787-2804. [CrossRef]
8. Jin J, Fan Z, Long Y, et al. Matrine induces ferroptosis in cervical cancer through activation of piezo1 channel. Phytomedicine. 2024;122:155165. [CrossRef]
9. Basak P, Sadhukhan P, Sarkar P, Sil PC. Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy. Toxicol Rep. 2017;4:306-318. [CrossRef]
10. Song Y, Wang M, Zhao S, Tian Y, Zhang C. Matrine promotes mitochondrial biosynthesis and reduces oxidative stress in experimental optic neuritis. Front Pharmacol. 2022;13:936632. [CrossRef]
11. Chen L, Chen L, Wan L, et al. Matrine improves skeletal muscle atrophy by inhibiting E3 ubiquitin ligases and activating the Akt/mTOR/FoxO3α signaling pathway in C2C12 myotubes and mice. Oncol Rep. 2019;42(2):479-494. [CrossRef]
12. Ali MS, Hussein RM, Gaber Y, Hammam OA, Kandeil MA. Modulation of JNK-1/ β-catenin signaling by Lactobacillus casei, inulin and their combination in 1,2-dimethylhydrazine-induced colon cancer in mice. RSC Adv. 2019;9(50):29368-29383. [CrossRef]
13. Fang R, Wu R, Zuo Q, et al. Sophora flavescens containing-QYJD formula activates Nrf2 anti-oxidant response, blocks cellular transformation and protects against DSS-induced colitis in mouse model. Am J Chin Med. 2018:1-15. [CrossRef]
14. Feng Z, Sun N, Noor F, et al. Matrine targets BTF3 to inhibit the growth of canine mammary tumor cells. Int J Mol Sci. 2023;25(1):540. [CrossRef]
15. Liu J, Guo Y, Cao J. Matrine triggers colon cancer cell apoptosis and G0/G1 cell cycle arrest via mediation of microRNA-22. Phytother Res. 2020;34(7):1619-1628. [CrossRef]
16. Zhao K, He B, Xue K, et al. IL6ST: A novel therapeutic target for managing and treating colorectal cancer via ferroptosis. Turk J Gastroenterol. 2024;35(9):690-698. [CrossRef]
17. Verhagen MP, Joosten R, Schmitt M, et al. Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation. Nat Genet. 2024;56(7):1456-1467. [CrossRef]
18. Yao D, Dong M, Dai C, Wu S. Inflammation and inflammatory cytokine contribute to the initiation and development of ulcerative colitis and its associated cancer. Inflamm Bowel Dis. 2019;25(10):1595-1602. [CrossRef]
19. De Simone V, Franzè E, Ronchetti G, et al. Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene. 2015;34(27):3493-3503. [CrossRef]
20. Hirano T, Hirayama D, Wagatsuma K, Yamakawa T, Yokoyama Y, Nakase H. Immunological mechanisms in inflammation-associated colon carcinogenesis. Int J Mol Sci. 2020;21(9):3062. [CrossRef]
21. Wang D, DuBois RN. PPARδ and PGE(2) signaling pathways communicate and connect inflammation to colorectal cancer. Inflamm Cell Signal. 2014;1(6):10.14800/ics.338. [CrossRef]
22. Tong Y, Hao Y, Gao X, Sun Y, Wang W. Dexamethasone combined metronidazole on mammary duct ectasia and its relationship with serum IL-10 and IL-17. J Obstet Gynaecol Res. 2020;46(10):2134-2141. [CrossRef]
23. Abdelaziz I, Bounaama A, Djerdjouri B, Amir-Tidadini ZC. Low-dose dimethylfumarate attenuates colitis-associated cancer in mice through M2 macrophage polarization and blocking oxidative stress. Toxicol Appl Pharmacol. 2024;489:117018. [CrossRef]
24. Yang Q, Han B, Li S, et al. The link between deacetylation and hepatotoxicity induced by exposure to hexavalent chromium. J Adv Res. 2022;35:129-140. [CrossRef]
25. Chang D, Wang F, Zhao YS, Pan HZ. Evaluation of oxidative stress in colorectal cancer patients. Biomed Environ Sci. 2008;21(4):286-289. [CrossRef]
26. Zińczuk J, Maciejczyk M, Zaręba K, et al. Pro-oxidant enzymes, redox balance and oxidative damage to proteins, lipids and DNA in colorectal cancer tissue. Is oxidative stress dependent on tumour budding and inflammatory infiltration? Cancers (Basel). 2020;12(6):1636. [CrossRef]
27. Ding N, Zhang T, Yu X, Zhuang S. T-box transcription factor 2 enhances chemoresistance of endometrial cancer by mediating NRF2 expression. Curr Protein Pept Sci. 2022;23(8):563-570. [CrossRef]
28. Robertson RP. Nrf2 and antioxidant response in animal models of type 2 diabetes. Int J Mol Sci. 2023;24(4):3082. [CrossRef]
29. Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Aspects Med. 2011;32(4-6):234-246. [CrossRef]
30. Han B, Li S, Lv Y, et al. Dietary melatonin attenuates chromium-induced lung injury via activating the Sirt1/Pgc-1α/Nrf2 pathway. Food Funct. 2019;10(9):5555-5565. [CrossRef]