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Opuntia ficus-indica Extract and Isorhamnetin-3-O-Glucosyl-Rhamnoside Diminish Tumor Growth of Colon Cancer Cells Xenografted in Immune-Suppressed Mice through the Activation of Apoptosis Intrinsic Pathway

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Abstract

This study aimed to evaluate the effects of Opuntia ficus-indica extract (OFI-E) and its glycoside isorhamnetin-3-O-glucosyl-rhamnoside (IGR) on the growth of human colorectal adenocarcinoma cells and in a xenografted-immunosuppressed mice model. The IC50 values of OFI-E and IGR on colon cancer cells (HT-29 RFP) were determinate, as well as their effects on the cell cycle and apoptosis induction. OFI-E and IGR produced an increased in apoptosis induction, ROS production and a G0/G1 cell cycle arrest. In xenografted-inmunosupressed mice, OFI-E and IGR reduced the tumor growth rate, myeloperoxidase activity and total cholesterol levels. OFI-E and IGR reduced the tumor growth through the overexpression of cleaved Caspase-9, Hdac11, and Bai1 proteins. OFI-E reduced the expression of bcl-2. Results demonstrated the chemopreventive effects of OFI-E, and its purified compound IGR, showing their potential as an alternative in the treatment of colorectal cancer.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Rocchetti G, Pellizzoni M, Montesano D et al (2018) Italian Opuntia ficus-indica cladodes as rich source of bioactive compounds with health-promoting properties. Foods 7(2):24. https://doi.org/10.3390/foods7020024

    Article  CAS  PubMed Central  Google Scholar 

  2. Antunes-Ricardo M, Moreno-García BE, Gutiérrez-Uribe JA et al (2014) Induction of apoptosis in colon cancer cells treated with isorhamnetin glycosides from Opuntia ficus-indica pads. Plant Foods Hum Nutr 69:331–336. https://doi.org/10.1007/s11130-014-0438-5

    Article  CAS  PubMed  Google Scholar 

  3. Moussa-Ayoub TE, Abd El-Hady E-SA, Omran HT et al (2014) Influence of cultivar and origin on the flavonol profile of fruits and cladodes from cactus Opuntia ficus-indica. Food Res Int 64:864–872. https://doi.org/10.1016/j.foodres.2014.08.021

    Article  CAS  PubMed  Google Scholar 

  4. Matias A, Nunes SL, Poejo J et al (2014) Antioxidant and anti-inflammatory activity of a flavonoid-rich concentrate recovered from Opuntia ficus-indica juice. Food Funct 5:3269–3280. https://doi.org/10.1039/C4FO00071D

    Article  CAS  PubMed  Google Scholar 

  5. Serra AT, Poejo J, Matias AA et al (2013) Evaluation of Opuntia spp. derived products as antiproliferative agents in human colon cancer cell line (HT29). Food Res Int 54:892–901. https://doi.org/10.1016/j.foodres.2013.08.043

    Article  CAS  Google Scholar 

  6. Antunes-Ricardo M, Hernández-Reyes A, Uscanga-Palomeque AC et al (2019) Isorhamnetin glycoside isolated from Opuntia ficus-indica (L.) MilI induces apoptosis in human colon cancer cells through mitochondrial damage. Chem Biol Interact 310(108734). https://doi.org/10.1016/j.cbi.2019.108734

  7. Ressaissi A, Attia N, Falé PL et al (2017) Isorhamnetin derivatives and piscidic acid for hypercholesterolemia: cholesterol permeability, HMG-CoA reductase inhibition, and docking studies. Arch Pharm Res 40:1278–1286. https://doi.org/10.1007/s12272-017-0959-1

    Article  CAS  PubMed  Google Scholar 

  8. Antunes-Ricardo M, Gutiérrez-Uribe JA, López-Pacheco F et al (2015) In vivo anti-inflammatory effects of isorhamnetin glycosides isolated from Opuntia ficus-indica (L.) mill cladodes. Ind Crop Prod 76:803–808. https://doi.org/10.1016/j.indcrop.2015.05.089

    Article  CAS  Google Scholar 

  9. Antunes-Ricardo M, Gutiérrez-Uribe JA, Martínez-Vitela C, Serna-Saldívar SO (2015) Topical anti-inflammatory effects of isorhamnetin glycosides isolated from Opuntia ficus-indica. Biomed Res Int 2015:1–9. https://doi.org/10.1155/2015/847320

    Article  CAS  Google Scholar 

  10. Hu S, Huang L, Meng L et al (2015) Isorhamnetin inhibits cell proliferation and induces apoptosis in breast cancer via Akt and mitogen-activated protein kinase kinase signaling pathways. Mol Med Rep 12:6745–6751. https://doi.org/10.3892/mmr.2015.4269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhang B-Y, Wang Y-M, Gong H et al (2015) Isorhamnetin flavonoid synergistically enhances the anticancer activity and apoptosis induction by cis-platin and carboplatin in non-small cell lung carcinoma (NSCLC). Int J Clin Exp Pathol 8:25–37

    PubMed  PubMed Central  Google Scholar 

  12. Boubaker J, Bhouri W, Ben Sghaier M et al (2011) Ethyl acetate extract and its major constituent, isorhamnetin 3-O-rutinoside, from Nitraria retusa leaves, promote apoptosis of human myelogenous erythroleukaemia cells: N. retusa leaf extracts promote apoptosis. Cell Prolif 44:453–461. https://doi.org/10.1111/j.1365-2184.2011.00772.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Li Y, Duan S, Jia H et al (2014) Flavonoids from tartary buckwheat induce G2/M cell cycle arrest and apoptosis in human hepatoma HepG2 cells. Acta Biochim Biophys Sin 46:460–470. https://doi.org/10.1093/abbs/gmu023

    Article  CAS  PubMed  Google Scholar 

  14. Kim J-E, Lee D-E, Lee KW et al (2011) Isorhamnetin suppresses skin cancer through direct inhibition of MEK1 and PI3-K. Cancer Prev Res 4:582–591. https://doi.org/10.1158/1940-6207.CAPR-11-0032

    Article  CAS  Google Scholar 

  15. Mileo AM, Nisticò P, Miccadei S (2019) Polyphenols: immunomodulatory and therapeutic implication in colorectal cancer. Front Immunol 10:729. https://doi.org/10.3389/fimmu.2019.00729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mariani F, Roncucci L (2017) Role of the vanins–myeloperoxidase axis in colorectal carcinogenesis. Int J Mol Sci 18:918. https://doi.org/10.3390/ijms18050918

    Article  CAS  PubMed Central  Google Scholar 

  17. Koshak AE, Abdallah HM, Esmat A, Rateb ME (2020) Anti-inflammatory activity and chemical characterisation of Opuntia ficus-indica seed oil cultivated in Saudi Arabia. Arab J Sci Eng 45:4571–4578. https://doi.org/10.1007/s13369-020-04555-x

    Article  CAS  Google Scholar 

  18. Ganji PN, Park W, Wen J et al (2013) Antiangiogenic effects of ganetespib in colorectal cancer mediated through inhibition of HIF-1α and STAT-3. Angiogenesis 16:903–917. https://doi.org/10.1007/s10456-013-9364-7

    Article  CAS  PubMed  Google Scholar 

  19. Hirano G, Izumi H, Kidani A et al (2010) Enhanced expression of PCAF endows apoptosis resistance in cisplatin-resistant cells. Mol Cancer Res 8:864–872. https://doi.org/10.1158/1541-7786.MCR-09-0458

    Article  CAS  PubMed  Google Scholar 

  20. Su M-Q, Zhou Y-R, Rao X et al (2018) Baicalein induces the apoptosis of HCT116 human colon cancer cells via the upregulation of DEPP/Gadd45a and activation of MAPKs. Int J Oncol. https://doi.org/10.3892/ijo.2018.4402

  21. Yang W-W, Shu B, Zhu Y, Yang H-T (2008) E2F6 inhibits cobalt chloride-mimetic hypoxia-induced apoptosis through E2F1. Mol Biol Cell 19:3691–3700. https://doi.org/10.1091/mbc.e08-02-0171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Giangrande PH (2004) A role for E2F6 in distinguishing G1/S- and G2/M-specific transcription. Genes Dev 18:2941–2951. https://doi.org/10.1101/gad.1239304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ryu MJ, Chung HS (2015) [10]-Gingerol induces mitochondrial apoptosis through activation of MAPK pathway in HCT116 human colon cancer cells. In Vitro Cell Dev Biol Anim 51:92–101. https://doi.org/10.1007/s11626-014-9806-6

  24. Nogueira V, Patra KC, Hay N (2018) Selective eradication of cancer displaying hyperactive Akt by exploiting the metabolic consequences of Akt activation. eLife 7:e32213. https://doi.org/10.7554/eLife.32213

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pandey P, Sayyed U, Tiwari RK et al (2019) Hesperidin induces ROS-mediated apoptosis along with cell cycle arrest at G2/M phase in human gall bladder carcinoma. Nutr Cancer 71:676–687. https://doi.org/10.1080/01635581.2018.1508732

    Article  CAS  PubMed  Google Scholar 

  26. Tavsan Z, Kayali HA (2019) Flavonoids showed anticancer effects on the ovarian cancer cells: involvement of reactive oxygen species, apoptosis, cell cycle and invasion. Biomed Pharmacother 116:109004. https://doi.org/10.1016/j.biopha.2019.109004

    Article  CAS  PubMed  Google Scholar 

  27. Choi YH (2019) Isorhamnetin induces ROS-dependent cycle arrest at G2/M phase and apoptosis in human hepatocarcinoma Hep3B cells. Gen Physiol Biophys 38:473–484. https://doi.org/10.4149/gpb_2019038

  28. Tang D, Kang R, Berghe TV et al (2019) The molecular machinery of regulated cell death. Cell Res 29:347–364. https://doi.org/10.1038/s41422-019-0164-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ding L, Biswas S, Morton RE et al (2012) Akt3 deficiency in macrophages promotes foam cell formation and atherosclerosis in mice. Cell Metab 15:861–872. https://doi.org/10.1016/j.cmet.2012.04.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ding L, Zhang L, Biswas S et al (2017) Akt3 inhibits adipogenesis and protects from diet-induced obesity via signaling pathway. JCI Insight 2:e95687. https://doi.org/10.1172/jci.insight.95687

    Article  PubMed Central  Google Scholar 

  31. Kim J, Jho KH, Choi YH, Nam S-Y (2013) Chemopreventive effect of cactus (Opuntia humifusa) extracts: radical scavenging activity, pro-apoptosis, and anti-inflammatory effect in human colon (SW480) and breast cancer (MCF7) cells. Food Funct 4:681. https://doi.org/10.1039/c3fo30287c

    Article  CAS  PubMed  Google Scholar 

  32. Villagra A, Cheng F, Wang H-W et al (2009) The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance. Nat Immunol 10:92–100. https://doi.org/10.1038/ni.1673

    Article  CAS  PubMed  Google Scholar 

  33. Townsend MH, Felsted AM, Piccolo SR et al (2018) Metastatic colon adenocarcinoma has a significantly elevated expression of IL-10 compared with primary colon adenocarcinoma tumors. Cancer Biol Ther 19:913–920. https://doi.org/10.1080/15384047.2017.1360453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Verón HE, Gauffin Cano P, Fabersani E et al (2019) Cactus pear (Opuntia ficus-indica) juice fermented with autochthonous lactobacillus plantarum S-811. Food Funct 10:1085–1097. https://doi.org/10.1039/C8FO01591K

    Article  PubMed  Google Scholar 

  35. Dong M, Lin J, Lim W et al (2018) Role of brown adipose tissue in metabolic syndrome, aging, and cancer cachexia. Front Med 12:130–138. https://doi.org/10.1007/s11684-017-0555-2

    Article  PubMed  Google Scholar 

  36. Ginzac A, Barres B, Chanchou M et al (2020) A decrease in brown adipose tissue activity is associated with weight gain during chemotherapy in early breast cancer patients. BMC Cancer 20:96. https://doi.org/10.1186/s12885-020-6591-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Duda DG, Sunamura M, Lozonschi L et al (2002) Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis. Br J Cancer 86:490–496. https://doi.org/10.1038/sj.bjc.6600067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Authors want to thank to the Consejo Nacional de Ciencia y Tecnología (CONACYT) and the Tecnologico de Monterrey (NutriOmics Research Group) and the donation of O. ficus-indica (L.) flour by Alimentos Funcionales Sociedad de Responsabilidad Limitada Microindustrial.

Funding

This work was supported by Consejo Nacional de Ciencia y Tecnología (CONACYT-CB Research Project 1168708).

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Author notes

  1. M. Antunes-Ricardo and D. Guardado-Félix contributed equally to this work.

Authors and Affiliations

  1. Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Centro de Biotecnología-FEMSA, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, N.L., Mexico

    M. Antunes-Ricardo, D. Guardado-Félix, J. Garza-Martínez, L. Acevedo-Pacheco, J. A. Gutiérrez-Uribe, J. Villela-Castrejón, F. López-Pacheco & S. O. Serna-Saldívar

  2. Tecnologico de Monterrey, Campus Puebla, Vía Atlixcáyotl 2301, C.P. 72453, Puebla, Puebla, Mexico

    M. R. Rocha-Pizaña & J. A. Gutiérrez-Uribe

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  1. M. Antunes-Ricardo
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Correspondence to J. A. Gutiérrez-Uribe or S. O. Serna-Saldívar.

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Ethical Statement

The animal experiment protocol was approved by the Institutional Committee on Care and Use of Experimental Animals (CICUAL) of the Tecnológico de Monterrey, Monterrey, Mexico.

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Antunes-Ricardo, M., Guardado-Félix, D., Rocha-Pizaña, M.R. et al. Opuntia ficus-indica Extract and Isorhamnetin-3-O-Glucosyl-Rhamnoside Diminish Tumor Growth of Colon Cancer Cells Xenografted in Immune-Suppressed Mice through the Activation of Apoptosis Intrinsic Pathway. Plant Foods Hum Nutr 76, 434–441 (2021). https://doi.org/10.1007/s11130-021-00934-3

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