Anti-tumoral Immunity and Chemo-preventive Effectiveness of Herbal Extracts of Curcumin, Ginger, Clove and Amygdaline in Ehrlich Ascites Carcinoma-Challenging Mice


Cite item

Full Text

Abstract

Background::Due to its systemic toxicity, traditional chemotherapy of tumors is being taken into consideration. Herbal therapy, containing phytochemical polyphenol derivatives such as Curcumin (Cur), Ginger (Gin), Cloves (Clov) and Amygdaline (Amyg), is one of the numerous complementary and alternative approaches as an anti-cancer therapy and holds great promise for cancer chemo-prevention with fewer side effects.

Aim::The current study was designated to assess anti-tumoral immunity and anti-cancer and chemo-preventive effectiveness of herbal extracts of Cur, Ginger, Clov and Amyg in Ehrlich Ascites Carcinoma (EAC)-challenging mice. Methods: Chemo-preventive efficacy of herbal extracts of Cur, Gin, Clov and Amyg were analyzed in vivo by examination of the apoptosis rate of EAC tumor cells by flow cytometry. The total numbers of EAC cells, splenocytes counts and leucocytes count with their differentials relative % in peripheral blood (PB) of EACchallenging mice were investigated.

Results::EAC-challenging mice treated with herbal extracts of Cur, Gin, Clov and Amyg showed a marked decline in EAC tumor cell count and a noticeable increase in apoptosis rate of EAC tumor cells, a remarkable decrease in serum level of cancer antigen 125 (CA-125) with an obvious increase in the number of splenocytes comparing to that in EAC-challenging mice treated with PBS alone. Moreover, the data indicated an insignificant change in the total leucocytes count and their differentials relative % of eosinophil, neutrophils, monocytes and lymphocytes in EAC-challenging mice treated with Cur and Amyg, but these parameters were markedly increased in EAC-challenging mice injected with Gin and Clov compared to that in EAC-challenging mice treated with PBS alone.

Conclusion::To conclude, the herbal extracts of Cur, Gin, Clov and Amyg may have anti-tumoral immunity and anti-cancer potency and potential to reduce the resistance to cancer conventional chemotherapy and exert cancer chemo-protective approaches with low adverse effects. Further research is necessary to determine the regimen's toxicity on various tissues and organs and to connect the diagnostic and therapeutic approaches used in the regimen's biomedical use.

About the authors

Soha Gomaa

Department of Zoology, Faculty of Science, Tanta University

Author for correspondence.
Email: info@benthamscience.net

Mohamed Nassef

Department of Zoology, Faculty of Science, Tanta University

Email: info@benthamscience.net

Randa El-Naggar

Department of Zoology, Faculty of Science, Tanta University

Email: info@benthamscience.net

Ahmed Massoud

Department of Zoology, Faculty of Science, Tanta University

Email: info@benthamscience.net

Mona El-Kholy

Department of Zoology, Faculty of Science, Tanta University

Email: info@benthamscience.net

References

  1. Torigoe, T.; Izumi, H.; Ishiguchi, H.; Yoshida, Y.; Tanabe, M.; Yoshida, T.; Igarashi, T.; Niina, I.; Wakasugi, T.; Imaizumi, T.; Momii, Y.; Kuwano, M.; Kohno, K. Cisplatin resistance and transcription factors. Curr. Med. Chem. Anticancer Agents, 2005, 5(1), 15-27. doi: 10.2174/1568011053352587 PMID: 15720258
  2. Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2021. CA Cancer J. Clin., 2021, 71(1), 7-33. doi: 10.3322/caac.21654 PMID: 33433946
  3. Lin, S.R.; Fu, Y.S.; Tsai, M.J.; Cheng, H.; Weng, C.F. Natural compounds from herbs that can potentially execute as autophagy inducers for cancer therapy. Int. J. Mol. Sci., 2017, 18(7), 1412. doi: 10.3390/ijms18071412 PMID: 28671583
  4. Ma, L.; Zhang, M.; Zhao, R.; Wang, D.; Ma, Y.; Ai, L. Plant natural products: Promising resources for cancer chemoprevention. Molecules, 2021, 26(4), 933. doi: 10.3390/molecules26040933 PMID: 33578780
  5. De Flora, S.; Ferguson, L.R. Overview of mechanisms of cancer chemopreventive agents. Mutat. Res., 2005, 591(1-2), 8-15. doi: 10.1016/j.mrfmmm.2005.02.029 PMID: 16107270
  6. George, B.P.; Chandran, R.; Abrahamse, H. Role of phytochemicals in cancer chemoprevention: Insights. Antioxidants, 2021, 10(9), 1455. doi: 10.3390/antiox10091455 PMID: 34573087
  7. Ramos, S. Cancer chemoprevention and chemotherapy: Dietary polyphenols and signalling pathways. Mol. Nutr. Food Res., 2008, 52(5), 507-526. doi: 10.1002/mnfr.200700326 PMID: 18435439
  8. Surh, Y.J. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer, 2003, 3(10), 768-780. doi: 10.1038/nrc1189 PMID: 14570043
  9. Noureini, S.K.; Wink, M. Antiproliferative effects of crocin in HepG2 cells by telomerase inhibition and hTERT down-regulation. Asian Pac. J. Cancer Prev., 2012, 13(5), 2305-2309. doi: 10.7314/APJCP.2012.13.5.2305 PMID: 22901211
  10. Elsayed, E.A.; Sharaf-Eldin, M.A.; El-Enshasy, H.A.; Wadaan, M. In vitro assessment of anticancer properties of Moringa peregrine essential seed oil on different cell lines. Pak. J. Zool., 2016, 48, 853-859.
  11. Xu, D.P.; Li, Y.; Meng, X.; Zhou, T.; Zhou, Y.; Zheng, J.; Zhang, J.J.; Li, H.B. Natural antioxidants in foods and medicinal plants: Extraction, assessment and resources. Int. J. Mol. Sci., 2017, 18(1), 96. doi: 10.3390/ijms18010096 PMID: 28067795
  12. Ouyang, L.; Luo, Y.; Tian, M.; Zhang, S.Y.; Lu, R.; Wang, J.H.; Kasimu, R.; Li, X. Plant natural products: from traditional compounds to new emerging drugs in cancer therapy. Cell Prolif., 2014, 47(6), 506-515. doi: 10.1111/cpr.12143 PMID: 25377084
  13. Pai, M.P.; Cottrell, M.L.; Kashuba, A.D.; Bertino, J.S. Pharmacokinetics and pharmacodynamics of anti-infective agents. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases; Elsevier: Amsterdam, The Netherlands, 2015, pp. 252-262.
  14. Chen, S.; Flower, A.; Ritchie, A.; Liu, J.; Molassiotis, A.; Yu, H.; Lewith, G. Oral Chinese herbal medicine (CHM) as an adjuvant treatment during chemotherapy for non-small cell lung cancer: A systematic review. Lung Cancer, 2010, 68(2), 137-145. doi: 10.1016/j.lungcan.2009.11.008 PMID: 20015572
  15. Fu, B.; Wang, N.; Tan, H.Y.; Li, S.; Cheung, F.; Feng, Y. Multi-component herbal products in the prevention and treatment of chemotherapy-associated toxicity and side effects: A review on experimental and clinical evidences. Front. Pharmacol., 2018, 9, 1394. doi: 10.3389/fphar.2018.01394 PMID: 30555327
  16. Serafini, M.; Stanzione, A.; Foddai, S.; Anton, R.; Delmulle, L. The European role on traditional herbal medicinal products and traditional plant food supplements. J. Clin. Gastroenterol., 2012, 46(Suppl.), S93-S94. doi: 10.1097/MCG.0b013e318266b08f PMID: 22955367
  17. Aung, T.; Qu, Z.; Kortschak, R.; Adelson, D. Understanding the effectiveness of natural compound mixtures in cancer through their molecular mode of action. Int. J. Mol. Sci., 2017, 18(3), 656. doi: 10.3390/ijms18030656 PMID: 28304343
  18. Gomez-Cadena, A.; Urueña, C.; Prieto, K.; Martinez-Usatorre, A.; Donda, A.; Barreto, A.; Romero, P.; Fiorentino, S. Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model. Cell Death Dis., 2016, 7(6), e2243. doi: 10.1038/cddis.2016.134 PMID: 27253407
  19. Saetang, J.; Tedasen, A.; Sangkhathat, S.; Sangkaew, N.; Dokduang, S.; Prompat, N.; Taraporn, S.; Graidist, P. Low piperine fractional piper nigrum extract enhanced the antitumor immunity via regulating the Th1/Th2/Treg cell subsets on NMU-induced tumorigenesis rats. Planta Med., 2022, 88(7), 527-537. doi: 10.1055/a-1458-5646 PMID: 33902130
  20. Lee, S.; Han, S.; Park, J.S.; Jeong, A.L.; Jung, S.H.; Choi, K.D.; Han, T-Y.; Han, I-Y.; Yang, Y. Herb mixture C5E aggravates doxorubicin-induced apoptosis of human breast cancer cell lines. J. Korean Soc. Appl. Biol. Chem., 2013, 56(5), 567-573. doi: 10.1007/s13765-013-3195-5
  21. Wang, Z.; Xie, C.; Huang, Y.; Lam, C.W.K.; Chow, M.S.S. Overcoming chemotherapy resistance with herbal medicines: Past, present and future perspectives. Phytochem. Rev., 2014, 13(1), 323-337. doi: 10.1007/s11101-013-9327-z
  22. Chen, S.; Wang, Z.; Huang, Y.; O’Barr, S.A.; Wong, R.A.; Yeung, S.; Chow, M.S.S. Ginseng and anticancer drug combination to improve cancer chemotherapy: A critical review. Evid. Based Complement. Alternat. Med., 2014, 2014, 1-13. doi: 10.1155/2014/168940 PMID: 24876866
  23. Koh, Y.C.; Ho, C.T.; Pan, M.H. Recent advances in cancer chemoprevention with phytochemicals. Yao Wu Shi Pin Fen Xi, 2020, 28(1), 14-37. doi: 10.38212/2224-6614.1219 PMID: 31883602
  24. Shukla, Y.; Pal, S.K. Dietary cancer chemoprevention: An overview. Int. J. Hum. Genet., 2004, 4(4), 265-276.v. doi: 10.1080/09723757.2004.11885905
  25. Konga, A.K.; Muchandi, A.S.; Ponnaiah, G.P. Soxhlet extraction of Spirogyra sp. algae: An alternative fuel. Biofuels, 2017, 8(1), 29-35. doi: 10.1080/17597269.2016.1196328
  26. Halle, W.; Halder, M.; Worth, A.; Genschow, E. The Registry of Cytotoxicity: Toxicity testing in cell cultures to predict acute toxicity (LD50) and to reduce testing in animals. Altern. Lab. Anim., 2003, 31(2), 89-198. doi: 10.1177/026119290303100204 PMID: 15612878
  27. Gothoskar, S.V.; Ranadive, K.J. Anticancer screening of SAN-AB: An extract of marking nut, Semecarpus anacardium. Indian J. Exp. Biol., 1971, 9(3), 372-375. PMID: 5144337
  28. Abdel Salam, S.R.; Salem, M.; Nassef, M.; Abdu, S.; El-Adl, R. Efficacy of combined administration of chemoimmunotherapy with bone marrow cells or granulocyte-colony stimulating factor-mobilized stem cells on expansion of myeloid and stem cells. Clin. Cancer Investig. J., 2017, 6(1), 73-80. doi: 10.4103/ccij.ccij_4_17
  29. Nassef, M. Immunobiochemical modulations caused by clomazone in Swiss albino mice. J. Basic Appl. Zool., 2017, 78, 1-8.
  30. Gomaa, S. Adverse effects induced by diclofenac, ibuprofen, and paracetamol toxicity on immunological and biochemical parameters in Swiss albino mice. J. Basic Appl. Zool., 2018, 79(1), 1-9.
  31. Fang, C.; Cao, Y.; Liu, X.; Zeng, X.T.; Li, Y. Serum CA125 is a predictive marker for breast cancer outcomes and correlates with molecular subtypes. Oncotarget, 2017, 8(38), 63963-63970. doi: 10.18632/oncotarget.19246 PMID: 28969044
  32. Mondal, J.; Bishayee, K.; Panigrahi, A.K.; Khuda-Bukhsh, A.R. Low doses of ethanolic extract of Boldo (Peumus boldus) can ameliorate toxicity generated by cisplatin in normal liver cells of mice in vivo and in WRL-68 cells in vitro, but not in cancer cells in vivo or in vitro. J. Integr. Med., 2014, 12(5), 425-438. doi: 10.1016/S2095-4964(14)60045-5 PMID: 25292342
  33. Lai, C.S.; Ho, C.T.; Pan, M.H. The cancer chemopreventive and therapeutic potential of tetrahydrocurcumin. Biomolecules, 2020, 10(6), 831. doi: 10.3390/biom10060831 PMID: 32486019
  34. Rasmussen, P. Potion or poison? Ginger. J. Prim. Health Care, 2011, 3(3), 235-236. doi: 10.1071/HC11235 PMID: 21892429
  35. Zadorozhna, M.; Mangieri, D. Mechanisms of chemopreventive and therapeutic proprieties of ginger extracts in cancer. Int. J. Mol. Sci., 2021, 22(12), 6599. doi: 10.3390/ijms22126599 PMID: 34202966
  36. Kubatka, P.; Uramova, S.; Kello, M.; Kajo, K.; Kruzliak, P.; Mojzis, J.; Vybohova, D.; Adamkov, M.; Jasek, K.; Lasabova, Z.; Zubor, P.; Fialova, S.; Dokupilova, S.; Solar, P.; Pec, M.; Adamicova, K.; Danko, J.; Adamek, M.; Busselberg, D. Antineoplastic effects of clove buds (Syzygium aromaticum L.) in the model of breast carcinoma. J. Cell. Mol. Med., 2017, 21(11), 2837-2851. doi: 10.1111/jcmm.13197 PMID: 28524540
  37. Park, H.J.; Yoon, S.H.; Han, L.S.; Zheng, L.T.; Jung, K.H.; Uhm, Y.K.; Lee, J.H.; Jeong, J.S.; Joo, W.S.; Yim, S.V.; Chung, J.H.; Hong, S.P. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells. World J. Gastroenterol., 2005, 11(33), 5156-5161. PMID: 16127745
  38. Chen, Y.; Ma, J.; Wang, F.; Hu, J.; Cui, A.; Wei, C.; Yang, Q.; Li, F. Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells. Immunopharmacol. Immunotoxicol., 2013, 35(1), 43-51. doi: 10.3109/08923973.2012.738688 PMID: 23137229
  39. Barakat, H.; Aljutaily, T.; Almujaydil, M.S.; Algheshairy, R.M.; Alhomaid, R.M.; Almutairi, A.S.; Alshimali, S.I.; Abdellatif, A.A.H. Amygdalin: A Review on its characteristics, antioxidant potential, gastrointestinal microbiota intervention, anticancer therapeutic and mechanisms, toxicity, and encapsulation. Biomolecules, 2022, 12(10), 1514. doi: 10.3390/biom12101514 PMID: 36291723
  40. Lin, S.; Wen, J.; Xu, X.; Shi, J.; Zhang, W.; Zheng, T.; Hou, Y.; Zhang, Y.; Li, Z.; Wang, K.; Jin, J.; Yue, L.; Abay, B.; Li, M.; Yue, Q.; Fan, L. Amygdalin induced mitochondria-mediated apoptosis of lung cancer cells via regulating nfκb-1/nfκb signaling cascade in vitro and in vivo. Am. J. Chin. Med., 2022, 50(5), 1361-1386. doi: 10.1142/S0192415X22500586 PMID: 35681261
  41. Hosny, S.; Sahyon, H.; Youssef, M.; Negm, A. Prunus Armeniaca L. seed extract and its amygdalin containing fraction induced mitochondrial-mediated apoptosis and autophagy in liver carcinogenesis. Anticancer. Agents Med. Chem., 2021, 21(5), 621-629. doi: 10.2174/1871520620666200608124003 PMID: 32510292
  42. Si, Z.; Zhang, B. Amygdalin attenuates airway epithelium apoptosis, inflammation, and epithelial-mesenchymal transition through restraining the tlr4/nf-kappab signaling pathway on lps-treated beas-2b bronchial epithelial cells. Int. Arch. Allergy Immunol., 2021, 182(10), 997-1007. doi: 10.1159/000514209 PMID: 34428767
  43. Alwan, A.M.; Afshari, J.T. In vivo growth inhibition of human caucasian prostate adenocarcinoma in nude mice induced by amygdalin with metabolic enzyme combinations. BioMed Res. Int., 2022, 2022, 1-7. doi: 10.1155/2022/4767621 PMID: 35637752
  44. Wang, R.; Zhang, D.; Tang, D.; Sun, K.; Peng, J.; Zhu, W.; Yin, S.; Wu, Y. Amygdalin inhibits TGFβ1-induced activation of hepatic stellate cells (HSCs) in vitro and CCl4-induced hepatic fibrosis in rats in vivo. Int. Immunopharmacol., 2021, 90, 107151. doi: 10.1016/j.intimp.2020.107151 PMID: 33296784
  45. Xiao, Z.; Ji, Q.; Fu, Y.D.; Gao, S.Q.; Hu, Y.H.; Liu, W. Amygdalin ameliorates liver fibrosis through inhibiting activation of tgf-beta/smad signaling. Chin. J. Integr. Med., 2021, 11, 1-9. PMID: 34816365
  46. Zhang, C.; Lin, J.; Zhen, C.; Wang, F.; Sun, X.; Kong, X.; Gao, Y. Amygdalin protects against acetaminophen-induced acute liver failure by reducing inflammatory response and inhibiting hepatocyte death. Biochem. Biophys. Res. Commun., 2022, 602, 105-112. doi: 10.1016/j.bbrc.2022.03.011 PMID: 35259588
  47. Al-Khafaji, K.; Taskin, T.T. Molecular dynamics simulation, free energy landscape and binding free energy computations in exploration the anti-invasive activity of amygdalin against metastasis. Comput. Methods Programs Biomed., 2020, 195, 105660. doi: 10.1016/j.cmpb.2020.105660 PMID: 32726718
  48. Park, W.; Amin, A.R.M.R.; Chen, Z.G.; Shin, D.M. New perspectives of curcumin in cancer prevention. Cancer Prev. Res. , 2013, 6(5), 387-400. doi: 10.1158/1940-6207.CAPR-12-0410 PMID: 23466484
  49. Shanmugam, M.; Rane, G.; Kanchi, M.; Arfuso, F.; Chinnathambi, A.; Zayed, M.; Alharbi, S.; Tan, B.; Kumar, A.; Sethi, G. The multifaceted role of curcumin in cancer prevention and treatment. Molecules, 2015, 20(2), 2728-2769. doi: 10.3390/molecules20022728 PMID: 25665066
  50. Yang, Z.J.; Huang, S.Y.; Zhou, D.D.; Xiong, R.G.; Zhao, C.N.; Fang, A.P.; Zhang, Y.J.; Li, H.B.; Zhu, H.L. Effects and mechanisms of curcumin for the prevention and management of cancers: An updated review. Antioxidants, 2022, 11(8), 1481. doi: 10.3390/antiox11081481 PMID: 36009200
  51. Palipoch, S.; Punsawad, C.; Koomhin, P.; Suwannalert, P. Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress. BMC Complement. Altern. Med., 2014, 14(1), 111. doi: 10.1186/1472-6882-14-111 PMID: 24674233
  52. Kim, Y.J.; Jeon, Y.; Kim, T.; Lim, W.C.; Ham, J.; Park, Y.N.; Kim, T.J.; Ko, H. Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-β1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells. Bioorg. Med. Chem. Lett., 2017, 27(4), 1081-1088. doi: 10.1016/j.bmcl.2016.12.042 PMID: 28110870
  53. Lechner, J.F.; Stoner, G.D. Gingers and their purified components as cancer chemopreventative agents. Molecules, 2019, 24(16), 2859. doi: 10.3390/molecules24162859 PMID: 31394732
  54. Wee, L.H.; Morad, N.A.; Aan, G.J.; Makpol, S.; Ngah, W.Z.W.; Yusof, Y.A.M. Mechanism of chemoprevention against colon cancer cells using combined Gelam honey and Ginger extract via mTOR and Wnt/β-catenin pathways. Asian Pac. J. Cancer Prev., 2015, 16(15), 6549-6556. doi: 10.7314/APJCP.2015.16.15.6549 PMID: 26434873
  55. Vemuri, SK; Banala, RR; Subbaiah, GPV; Srivastava, SK; Reddy, AG; Malarvili, T Anti-cancer potential of a mix of natural extracts of turmeric, ginger and garlic: A cell-based study. Egyptian J. Basic Appl. Sci., 2017, 4(4), 332-344. doi: 10.1016/j.ejbas.2017.07.005
  56. Yekta, Z.P.; Ebrahimi, S.M.; Hosseini, M.; Nasrabadi, A.N.; Sedighi, S.; Surmaghi, M.H.S.; Madani, H. Ginger as a miracle against chemotherapy-induced vomiting. Iran. J. Nurs. Midwifery Res., 2012, 17(5), 325-329. PMID: 23853643
  57. Lete, I.; Alluέ, J. The effectiveness of ginger in the prevention of nausea and vomiting during pregnancy and chemotherapy. Integrat. Med. Insightst, 2016, 11, S36273. doi: 10.4137/IMI.S36273
  58. Shukla, Y.; Singh, M. Cancer preventive properties of ginger: A brief review. Food Chem. Toxicol., 2007, 45(5), 683-690. doi: 10.1016/j.fct.2006.11.002 PMID: 17175086
  59. Zari, A.T.; Zari, T.A.; Hakeem, K.R. Anticancer properties of eugenol: A review. Molecules, 2021, 26(23), 7407. doi: 10.3390/molecules26237407 PMID: 34885992
  60. Fujisawa, S.; Murakami, Y. Eugenol and its role in chronic diseases. In: Drug Discovery from Mother Nature; Springer: Cham, 2016; pp. 45-66. doi: 10.1007/978-3-319-41342-6_3
  61. Moradi, B.; Heidari-Soureshjani, S.; Asadi-Samani, M.; Yang, Q. A systematic review of phytochemical and phytotherapeutic characteristics of bitter almond. Int. J. Pharmaceut. Phytopharmacol. Res., 2017, 7, 1-9.
  62. Christodoulou, P.; Boutsikos, P.; Neophytou, C.M.; Kyriakou, T.C.; Christodoulou, M.I.; Papageorgis, P.; Stephanou, A.; Patrikios, I. Amygdalin as a chemoprotective agent in co-treatment with cisplatin. Front. Pharmacol., 2022, 13, 1013692. doi: 10.3389/fphar.2022.1013692 PMID: 36204233
  63. Albogami, S.; Hassan, A.; Ahmed, N.; Alnefaie, A.; Alattas, A.; Alquthami, L.; Alharbi, A. Evaluation of the effective dose of amygdalin for the improvement of antioxidant gene expression and suppression of oxidative damage in mice. PeerJ., 2020, 8, e9232. doi: 10.7717/peerj.9232 PMID: 32509470
  64. Kitic, D.; Miladinovic, B.; Randjelovic, M.; Szopa, A.; Sharifi-Rad, J.; Calina, D.; Seidel, V. Anticancer potential and other pharmacological properties of (Prunus armeniaca L.): An updated overview. Plants, 2022, 11(14), 1885. doi: 10.3390/plants11141885 PMID: 35890519

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2024 Bentham Science Publishers