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Silymarin inhibits the progression of Ehrlich solid tumor via targeting molecular pathways of cell death, proliferation, angiogenesis, and metastasis in female mice

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Abstract

Background

Plant-derived phytochemicals have been reported to exert anticancer activity. This study investigated the antitumor role of silymarin (Silybum marianum) (SMN) and its molecular targets in Ehrlich solid tumor xenografts in vivo.

Methods and results

Female Swiss albino mice were divided into three groups (of five animals each) that were engrafted with Ehrlich tumor (ET) cells with or without SMN treatment. The 3rd groups treated with DMSO only vehicle control group. A significant reduction in animal body mass and tumor volume/weight were observed in xenografted mice treated with SMN. SMN modulated oxidative stress in tumors while enhancing the antioxidant levels in mouse serum. SMN activated both mitochondrial and death receptor-related apoptosis pathways and induced cell cycle arrest, marked by a significant downregulation of cyclin D1 in SMN-treated tumors. Significant decreases in RNA content and protein expression levels of Ki-67 and proliferating cell nuclear antigen were observed in ET cells. Additionally, SMN downregulated vascular endothelial growth factor and nuclear factor-kappa B levels indicating anti-angiogenesis activity of this agent. SMN upregulated the expression of E-cadherin in tumor tissue suggesting, that SMN has potential ability to inhibit metastasis. Tumor tissue from SMN-treated animals showed a remarkable degeneration and reduction in the neoplastic cell density.

Conclusions

The anticancer effect was associated with apparent apoptosis in neoplastic cells with abundance of multifocal necrotic areas. SMN was found to inhibit ET growth via enhancing apoptosis, inhibition of cell division and reduction in angiogenesis in vivo.

Graphical abstract

Hypothetical scheme of SMN antitumor effects (mechanism of signaling) in solid ET in vivo. SMN anticancer effect may be mediated by molecular mediators that affect proliferation, cell cycle activity, apoptotic pathways, angiogenesis, and metastasis.

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Data availability

All data generated or analyzed during this study are included in this published article.

References

  1. Kim SH, Choo GS, Yoo ES, Woo JS, Han SH, Lee JH, Jung JY (2019) Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells. Oncol Rep 42(5):1904–1914. https://doi.org/10.3892/or.2019.7295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mishra S, Tamta AK, Sarikhani M, Desingu PA, Kizkekra SM, Pandit AS, Kumar S, Khan D, Raghavan SC, Sundaresan NR (2018) Subcutaneous Ehrlich Ascites Carcinoma mice model for studying cancer-induced cardiomyopathy. Sci Rep 8(1):5599. https://doi.org/10.1038/s41598-018-23669-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. El-Missiry MA, Abd El-Aziz AF (2000) Influence of melatonin on proliferation and antioxidant system in Ehrlich ascites carcinoma cells. Cancer Lett 151(2):119–125. https://doi.org/10.1016/s0304-3835(99)00366-3

    Article  CAS  PubMed  Google Scholar 

  4. Abd Eldaim MA, Tousson E, Soliman MM, El Sayed IET, Abdel Aleem AAH, Elsharkawy HN (2021) Grape seed extract ameliorated Ehrlich solid tumor-induced hepatic tissue and DNA damage with reduction of PCNA and P53 protein expression in mice. Environ Sci Pollut Res Int 28(32):44226–44238. https://doi.org/10.1007/s11356-020-11857-y

    Article  CAS  PubMed  Google Scholar 

  5. Hazem RM, Mohamed AA, Ghareb N, Mehanna ET, Mesbah NM, Abo-Elmatty DM, Elgawish MS (2021) Anti-cancer activity of two novel heterocyclic compounds through modulation of VEGFR and miR-122 in mice bearing Ehrlich ascites carcinoma. Eur J Pharmacol 892:173747. https://doi.org/10.1016/j.ejphar.2020.173747

    Article  CAS  PubMed  Google Scholar 

  6. Feitosa IB, Mori B, Teles CBG, Costa AGD (2021) What are the immune responses during the growth of Ehrlich’s tumor in ascitic and solid form? Life Sci 264:118578. https://doi.org/10.1016/j.lfs.2020.118578

    Article  CAS  PubMed  Google Scholar 

  7. Alotaibi B, Tousson E, El-Masry TA, Altwaijry N, Saleh A (2020) Ehrlich ascites carcinoma as model for studying the cardiac protective effects of curcumin nanoparticles against cardiac damage in female mice. Environ Toxicol. https://doi.org/10.1002/tox.23016

    Article  PubMed  Google Scholar 

  8. Badr El-Din NK, Shabana SM, Abdulmajeed BA, Ghoneum M (2020) A novel kefir product (PFT) inhibits Ehrlich ascites carcinoma in mice via induction of apoptosis and immunomodulation. BMC Complement Med Ther 20(1):127. https://doi.org/10.1186/s12906-020-02901-y

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bhattacharya R, Chatterjee R, Mandal AKA, Mukhopadhyay A, Basu S, Giri AK, Chatterji U, Bhattacharjee P (2020) Theaflavin-containing black tea extract: a potential DNA methyltransferase inhibitor in human colon cancer cells and ehrlich ascites carcinoma-induced solid tumors in mice. Nutr Cancer 73:1–13. https://doi.org/10.1080/01635581.2020.1828943

    Article  CAS  Google Scholar 

  10. Abd Eldaim MA, Tousson E, El Sayed IET, Abd Elmaksoud AZ, Ahmed AAS (2021) Ameliorative effects of 9-diaminoacridine derivative against Ehrlich ascites carcinoma-induced hepatorenal injury in mice. Environ Sci Pollut Res Int 28(17):21835–21850. https://doi.org/10.1007/s11356-021-13904-8

    Article  CAS  PubMed  Google Scholar 

  11. Jahanafrooz Z, Motamed N, Rinner B, Mokhtarzadeh A, Baradaran B (2018) Silibinin to improve cancer therapeutic, as an apoptotic inducer, autophagy modulator, cell cycle inhibitor, and microRNAs regulator. Life Sci 213:236–247. https://doi.org/10.1016/j.lfs.2018.10.009

    Article  CAS  PubMed  Google Scholar 

  12. Zhu G, Pan C, Bei JX, Li B, Liang C, Xu Y, Fu X (2020) Mutant p53 in cancer progression and targeted therapies. Front Oncol 10:595187. https://doi.org/10.3389/fonc.2020.595187

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kwon HC, Kim SH, Oh SY, Lee S, Kwon KA, Lee JH, Choi HJ, Park KJ, Lee HS, Roh MS, Kim HJ (2010) Clinicopathological significance of nuclear factor-kappa B, HIF-1 alpha, and vascular endothelial growth factor expression in stage III colorectal cancer. Cancer Sci 101(6):1557–1561. https://doi.org/10.1111/j.1349-7006.2010.01553.x

    Article  CAS  PubMed  Google Scholar 

  14. Delmas D, Xiao J, Vejux A, Aires V (2020) Silymarin and cancer: a dual strategy in both in chemoprevention and chemosensitivity. Molecules 25(9):2009. https://doi.org/10.3390/molecules25092009

    Article  CAS  PubMed Central  Google Scholar 

  15. Fallah M, Davoodvandi A, Nikmanzar S, Aghili S, Mirazimi SMA, Aschner M, Rashidian A, Hamblin MR, Chamanara M, Naghsh N, Mirzaei H (2021) Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer. Biomed Pharmacother 142:112024. https://doi.org/10.1016/j.biopha.2021.112024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Verdura S, Cuyàs E, Ruiz-Torres V, Micol V, Joven J, Bosch-Barrera J, Menendez JA (2021) Lung cancer management with silibinin: a historical and translational perspective. Pharmaceuticals (Basel) 14(6):559. https://doi.org/10.3390/ph14060559

    Article  CAS  Google Scholar 

  17. Khakinezhad Tehrani F, Ranji N, Kouhkan F, Hosseinzadeh S (2021) PANC-1 cancer stem-like cell death with silybin encapsulated in polymersomes and deregulation of stemness-related miRNAs and their potential targets. Iran J Basic Med Sci 24(4):514–523. https://doi.org/10.22038/ijbms.2021.54001.12136

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kim SH, Choo GS, Yoo ES, Woo JS, Lee JH, Han SH, Jung SH, Kim HJ, Jung JY (2021) Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis. Oncol Lett 21(6):492. https://doi.org/10.3892/ol.2021.12753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Khater M, Greco F, Osborn HMI (2020) Antiangiogenic activity of flavonoids: a systematic review and meta-analysis. Molecules 25(20):4712. https://doi.org/10.3390/molecules25204712

    Article  CAS  PubMed Central  Google Scholar 

  20. Xie Y, Zhang D, Zhang J, Yuan J (2019) Metabolism, transport and drug-drug interactions of silymarin. Molecules 24(20):3693. https://doi.org/10.3390/molecules24203693

    Article  CAS  PubMed Central  Google Scholar 

  21. Heidarian E, Nouri A (2021) Hepatoprotective effects of silymarin against diclofenac-induced liver toxicity in male rats based on biochemical parameters and histological study. Arch Physiol Biochem 127(2):112–118. https://doi.org/10.1080/13813455.2019.1620785

    Article  CAS  PubMed  Google Scholar 

  22. Hosseinabadi T, Lorigooini Z, Tabarzad M, Salehi B, Rodrigues CF, Martins N, Sharifi-Rad J (2019) Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer. Phytother Res 33(11):2849–2861. https://doi.org/10.1002/ptr.6470

    Article  CAS  PubMed  Google Scholar 

  23. Vostálová J, Tinková E, Biedermann D, Kosina P, Ulrichová J, Rajnochová Svobodová A (2019) Skin protective activity of silymarin and its flavonolignans. Molecules 24(6):1022. https://doi.org/10.3390/molecules24061022

    Article  CAS  PubMed Central  Google Scholar 

  24. Yassin NYS, AbouZid SF, El-Kalaawy AM, Ali TM, Elesawy BH, Ahmed OM (2021) Tackling of renal carcinogenesis in wistar rats by Silybum marianum total extract, Silymarin, and Silibinin via modulation of oxidative stress, apoptosis, Nrf2, PPARγ, NF-κB, and PI3K/Akt signaling pathways. Oxid Med Cell Longev 2021:7665169. https://doi.org/10.1155/2021/7665169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. El-Far M, Salah N, Essam A, Abd El-Azim AO, El-Sherbiny IM (2018) Silymarin nanoformulation as potential anticancer agent in experimental Ehrlich ascites carcinoma-bearing animals. Nanomedicine (Lond) 13(15):1865–1858. https://doi.org/10.2217/nnm-2017-0394

    Article  CAS  Google Scholar 

  26. Cheng K-C, Asakawa A, Li Y-X, Chung H-H, Amitani H, Ueki T, Cheng J-T, Inui A (2014) Silymarin induces insulin resistance through an increase of phosphatase and tensin homolog in Wistar rats. PLoS ONE 9(1):e84550–e84550. https://doi.org/10.1371/journal.pone.0084550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang L, Huang Q-H, Li Y-X, Huang Y-F, Xie J-H, Xu L-Q, Dou Y-X, Su Z-R, Zeng H-F, Chen J-N (2018) Protective effects of silymarin on triptolide-induced acute hepatotoxicity in rats. Mol Med Rep 17(1):789–800. https://doi.org/10.3892/mmr.2017.7958

    Article  CAS  PubMed  Google Scholar 

  28. Othman AI, El-Sherbiny IM, ElMissiry MA, Ali DA, AbdElhakim E (2018) Polyphenon-E encapsulated into chitosan nanoparticles inhibited proliferation and growth of Ehrlich solid tumor in mice. Egypt J Basic Appl Sci 5(1):110–120. https://doi.org/10.1016/j.ejbas.2017.10.008

    Article  Google Scholar 

  29. Abdulwahab DA, El-Missiry MA, Shabana S, Othman AI, Amer ME (2021) Melatonin protects the heart and pancreas by improving glucose homeostasis, oxidative stress, inflammation and apoptosis in T2DM-induced rats. Heliyon 7(3):e06474. https://doi.org/10.1016/j.heliyon.2021.e06474

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ensley JF, Maciorowski Z, Pietraszkiewicz H, Klemic G, KuKuruga M, Sapareto S, Corbett T, Crissman J (1987) Solid tumor preparation for flow cytometry using a standard murine model. Cytometry 8(5):479–487. https://doi.org/10.1002/cyto.990080508

    Article  CAS  PubMed  Google Scholar 

  31. Ray RS, Ghosh B, Rana A, Chatterjee M (2007) Suppression of cell proliferation, induction of apoptosis and cell cycle arrest: chemopreventive activity of vanadium in vivo and in vitro. Int J Cancer 120(1):13–23. https://doi.org/10.1002/ijc.22277

    Article  CAS  PubMed  Google Scholar 

  32. Hamurcu Z, Demirtas H, Kumandas S (2006) Flow cytometric comparison of RNA content in peripheral blood mononuclear cells of Down syndrome patients and control individuals. Cytometry B: Clin Cytom: J Int Soc Anal Cytol 70(1):24–28. https://doi.org/10.1002/cyto.b.20077

    Article  Google Scholar 

  33. El-Missiry M, Othman A, Amer M, Mohamed E (2012) Ottelione A inhibited proliferation of Ehrlich ascites carcinoma cells in mice. Chem Biol Interact 200(2–3):119–127. https://doi.org/10.1016/j.cbi.2012.10.013

    Article  CAS  PubMed  Google Scholar 

  34. Janardhan KS, Jensen H, Clayton NP, Herbert RA (2018) Immunohistochemistry in investigative and toxicologic pathology. Toxicol Pathol 46(5):488–510. https://doi.org/10.1177/0192623318776907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Amer ME, Othamn AI, El-Missiry MA (2021) Melatonin ameliorates diabetes-induced brain injury in rats. Acta Histochem 123(2):151677. https://doi.org/10.1016/j.acthis.2020.151677

    Article  CAS  PubMed  Google Scholar 

  36. Anggorowati N, Ratna Kurniasari C, Damayanti K, Cahyanti T, Widodo I, Ghozali A, Romi MM, Sari DC, Arfian N (2017) Histochemical and Immunohistochemical Study of α-SMA collagen, and PCNA in epithelial ovarian neoplasm. Asian Pac J Cancer Prev: APJCP 18(3):667–671. https://doi.org/10.22034/APJCP.2017.18.3.667

    Article  PubMed  PubMed Central  Google Scholar 

  37. Imamoto R, Okano J-I, Sawada S, Fujise Y, Abe R, Murawaki Y (2014) Null anticarcinogenic effect of silymarin on diethylnitrosamine-induced hepatocarcinogenesis in rats. Exp Ther Med 7(1):31–38. https://doi.org/10.3892/etm.2013.1391

    Article  CAS  PubMed  Google Scholar 

  38. Deep G, Gangar SC, Rajamanickam S, Raina K, Gu M, Agarwal C, Oberlies NH, Agarwal R (2012) Angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer: targeting VEGF-VEGFR signaling. PLoS ONE 7(4):e34630. https://doi.org/10.1371/journal.pone.0034630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Su CH, Chen LJ, Liao JF, Cheng JT (2013) Increase of phosphatase and tensin homolog by silymarin to inhibit human pharynx squamous cancer. J Med Food 16(9):778–784. https://doi.org/10.1089/jmf.2012.2534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Won DH, Kim LH, Jang B, Yang IH, Kwon HJ, Jin B, Oh SH, Kang JH, Hong SD, Shin JA, Cho SD (2018) In vitro and in vivo anti-cancer activity of silymarin on oral cancer. Tumour Biol 40(5):1010428318776170. https://doi.org/10.1177/1010428318776170

    Article  CAS  PubMed  Google Scholar 

  41. Cho HJ, Suh DS, Moon SH, Song YJ, Yoon MS, Park DY, Choi KU, Kim YK, Kim KH (2013) Silibinin inhibits tumor growth through downregulation of extracellular signal-regulated kinase and Akt in vitro and in vivo in human ovarian cancer cells. J Agric Food Chem 61(17):4089–4096. https://doi.org/10.1021/jf400192v

    Article  CAS  PubMed  Google Scholar 

  42. Qiu X, Wang H, Wang Z, Fu Y, Yin J (2020) Expression of PCNA, Ki-67 and COX-2 in breast cancer based on DCE-MRI image information. J Infect Public Health 13(12):2032–2037. https://doi.org/10.1016/j.jiph.2019.06.024

    Article  PubMed  Google Scholar 

  43. Tchakarska G, Sola B (2020) The double dealing of cyclin D1. Cell Cycle 19(2):163–178. https://doi.org/10.1080/15384101.2019.1706903

    Article  CAS  PubMed  Google Scholar 

  44. Fan L, Ma Y, Liu Y, Zheng D, Huang G (2014) Silymarin induces cell cycle arrest and apoptosis in ovarian cancer cells. Eur J Pharmacol 743:79–88. https://doi.org/10.1016/j.ejphar.2014.09.019

    Article  CAS  PubMed  Google Scholar 

  45. Deep G, Singh RP, Agarwal C, Kroll DJ, Agarwal R (2006) Silymarin and silibinin cause G1 and G2-M cell cycle arrest via distinct circuitries in human prostate cancer PC3 cells: a comparison of flavanone silibinin with flavanolignan mixture silymarin. Oncogene 25(7):1053–1069. https://doi.org/10.1038/sj.onc.1209146

    Article  CAS  PubMed  Google Scholar 

  46. Ramakrishnan G, Lo Muzio L, Elinos-Báez CM, Jagan S, Augustine TA, Kamaraj S, Anandakumar P, Devaki T (2009) Silymarin inhibited proliferation and induced apoptosis in hepatic cancer cells. Cell Prolif 42(2):229–240. https://doi.org/10.1111/j.1365-2184.2008.00581.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gupta SC, Kim JH, Prasad S, Aggarwal BB (2010) Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev 29(3):405–434. https://doi.org/10.1007/s10555-010-9235-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jiang C, Agarwal R, Lü J (2000) Anti-angiogenic potential of a cancer chemopreventive flavonoid antioxidant, silymarin: inhibition of key attributes of vascular endothelial cells and angiogenic cytokine secretion by cancer epithelial cells. Biochem Biophys Res Commun 276(1):371–378. https://doi.org/10.1006/bbrc.2000.3474

    Article  CAS  PubMed  Google Scholar 

  49. Gloushankova NA, Rubtsova SN, Zhitnyak IY (2017) Cadherin-mediated cell-cell interactions in normal and cancer cells. Tissue Barriers 5(3):e1356900. https://doi.org/10.1080/21688370.2017.1356900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mendonsa AM, Na TY, Gumbiner BM (2018) E-cadherin in contact inhibition and cancer. Oncogene 37(35):4769–4780. https://doi.org/10.1038/s41388-018-0304-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Padmanaban V, Krol I, Suhail Y, Szczerba BM, Aceto N, Bader JS, Ewald AJ (2019) E-cadherin is required for metastasis in multiple models of breast cancer. Nature 573(7774):439–444. https://doi.org/10.1038/s41586-019-1526-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Corso G, Figueiredo J, De Angelis SP, Corso F, Girardi A, Pereira J, Seruca R, Bonanni B, Carneiro P, Pravettoni G, Guerini Rocco E, Veronesi P, Montagna G, Sacchini V, Gandini S (2020) E-cadherin deregulation in breast cancer. J Cell Mol Med 24(11):5930–5936. https://doi.org/10.1111/jcmm.15140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Patel M, Horgan PG, McMillan DC, Edwards J (2018) NF-κB pathways in the development and progression of colorectal cancer. Transl Res 197:43–56. https://doi.org/10.1016/j.trsl.2018.02.002

    Article  CAS  PubMed  Google Scholar 

  54. Ryan KM, Ernst MK, Rice NR, Vousden KH (2000) Role of NF-kappaB in p53-mediated programmed cell death. Nature 404(6780):892–897. https://doi.org/10.1038/35009130

    Article  CAS  PubMed  Google Scholar 

  55. Marnett LJ (1999) Lipid peroxidation-DNA damage by malondialdehyde. Mutat Res 424(1–2):83–95. https://doi.org/10.1016/s0027-5107(99)00010-x

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Facilities provided by Mansoura University are greatly acknowledged.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Zoology Department, Faculty of Sciences, Mansoura University, Mansoura, Egypt

    Maggie E. Amer, Maher A. Amer, Azza I. Othman, Doaa A. Elsayed & Mohamed Amr El-Missiry

  2. Basic Science Department, Delta University for Science and Technology, Gamasa, Egypt

    Omar A. Ammar

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by MEA, MAA, AIO, DAE, MAE, OAA. The first draft of the manuscript was written and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Maggie E. Amer or Mohamed Amr El-Missiry.

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All procedures performed in this study were conducted in accordance with the regulations approved by the Ethics Committee at Faculty of Science, Mansoura University, Egypt.

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Amer, M.E., Amer, M.A., Othman, A.I. et al. Silymarin inhibits the progression of Ehrlich solid tumor via targeting molecular pathways of cell death, proliferation, angiogenesis, and metastasis in female mice. Mol Biol Rep 49, 4659–4671 (2022). https://doi.org/10.1007/s11033-022-07315-2

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