Skip to main content
SpringerLink
Log in

In-vivo antiproliferative activity of Morus latifolia leaf and bark extracts against Ehrlich’s ascites carcinoma

  • Original Article
  • Published:
Toxicological Research Aims and scope Submit manuscript

Abstract

Cancer is the second death causing disease all over the world and until today 100 different types of cancer have been identified whose treatment methods consist of serious side effects on human body. To reduce the frequency of adverse effects of cancer treatment, nowadays plant derived natural components are getting priority. The plant Morus latifolia is widely available in northern part of Bangladesh. The earlier researches suggested that popular varieties of some Morus sp. like Morus alba, Morus indica etc. have good anti-proliferative activity. Hence, this study was designed to evaluate the anti-proliferative activity of leaf and bark extracts of M. latifolia against Ehrlich’s ascites carcinoma (EAC) in vivo. The leaf and bark extracts of M. latifolia were used in several bioassays including Brine shrimp lethality test, hemagglutination activity test, antioxidant activity test, and cell growth inhibition test. Besides, fluorescence microscopy was performed to study apoptotic features in EAC cells, and molecular analysis like real-time PCR were also conducted. The results of Brine shrimp lethality test, hemagglutination activity test, and antioxidant activity assay supported the cell growth inhibition capability of leaf and bark extracts which was confirmed by in vivo cell growth inhibition bioassay. Moreover, the experimental extracts were able to induce cell apoptotis through altering the expression pattern of Bcl-2 and Bax genes. All of the results of this study suggest that several noble compounds are present in M. latifolia plant extracts which are capable for healing cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Todaro M, Bonanno A, Tornambè G, Di Grigoli A, Luisa Scatassa M, Giaccone P (2009) Utilization of mulberry leaves (Morus latifolia cv. Kokusou 21) in diets for dairy ewes. Ital J Anim Sci 8:438–440

    Google Scholar 

  2. Bernal J, Mendiola JA, Ibez E, Cifuentes A (2011) Advanced analysis of nutraceuticals. J Pharm Bbiomed Anal 55:758–775

    CAS  Google Scholar 

  3. Iqbal S, Younas U, Chan KW, Sarfraz RA, Uddin MK (2012) Proximate composition and antioxidant potential of leaves from three varieties of Mulberry (Morus sp.): a comparative study. Int J Mol Sci 13:6651–6664

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Islam MS, Rahi MS, Koli HK, Jerin I, Sajib SA, Hoque KMF, Reza MA (2018) Evaluation of phytochemical, antioxidant, cytotoxicity and in vitro antibacterial activity of aqueous extract of Ganoderma lucidum cultivated in Bangladeshi habitat. Malaya J Biosci 5:1–13

    CAS  Google Scholar 

  5. Niemi M, Sthle G (2016) The use of ayurvedic medicine in the context of health promotiona mixed methods case study of an ayurvedic centre in Sweden. BMC Complement Altern Med 16:62–75

    PubMed  PubMed Central  Google Scholar 

  6. Narayanaswamy V (1981) Origin and development of ayurveda:(a brief history). Anc Sci Life 1:1–7

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Hou DX (2003) Potential mechanisms of cancer chemoprevention by anthocyanins. Curr Mol Med 3:149–159

    CAS  PubMed  Google Scholar 

  8. Islam MS, Rahi MS, Jerin I, Hasan KE, Sajib SA, Ferdaus KMKB, Hoque KMF, Reza MA (2017) Antiproliferative, antioxidant and antibacterial activity of seed extract of Thuja occidentalis. Int J Biosci 11:372–386

    Google Scholar 

  9. Al-Mamun MA, Husna J, Khatun M, Hasan R, Kamruzzaman M, Hoque KMF, Reza MA, Ferdousi Z (2016) Assessment of antioxidant, anticancer and antimicrobial activity of two vegetable species of Amaranthus in Bangladesh. BMC Complement Altern Med 16:157–167

    PubMed  PubMed Central  Google Scholar 

  10. Tagne RS, Telefo BP, Nyemb JN, Yemele DM, Njina SN, Goka SMC, Lienou LL, Kamdje AHN, Moundipa PF, Farooq AD (2014) Anticancer and antioxidant activities of methanol extracts and fractions of some Cameroonian medicinal plants. Asian Pac J Trop Med 7:S442–S447

    Google Scholar 

  11. Krishnamoorthy M, Ashwini P (2011) Anticancer activity of Cynodon dactylon L. extract on Ehrlich ascites carcinoma. J Environ Res Dev 5:551–557

    Google Scholar 

  12. Fadeyi SA, Fadeyi OO, Adejumo AA, Okoro C, Myles EL (2013) In vitro anticancer screening of 24 locally used Nigerian medicinal plants. BMC Complement Altern Med 13:79–87

    PubMed  PubMed Central  Google Scholar 

  13. Cragg G, Newman D (2003) Plants as a source of anticancer and anti HIV agents. Ann Appl Biol 143:127–133

    CAS  Google Scholar 

  14. Gao PF, Watanabe K (2011) Introduction of the World Health Organization project of the international classification of traditional medicine. Zhong Xi Yi Jie He Xue Bao 9:1161–1164

    PubMed  Google Scholar 

  15. Ferguson LR, Chen H, Collins AR, Connell M, Damia G, Dasgupta S, Malhotra M, Meeker AK, Amedei A, Amin A (2015) Genomic instability in human cancer: molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition. Semin Cancer Biol 35:5–24

    Google Scholar 

  16. Bernstein C, Bernstein H (2015) Epigenetic reduction of DNA repairs in progression to gastrointestinal cancer. World J Gastrointest Oncol 7:30–46

    PubMed  PubMed Central  Google Scholar 

  17. Du L, Kim JJ, Chen B, Zhu S, Dai N (2017) Marital status is associated with superior survival in patients with esophageal cancer: a Surveillance, Epidemiology, and End Results study. Oncotarget 8:95965–95972

    PubMed  PubMed Central  Google Scholar 

  18. Roukos DH (2009) Genome wide association studies: how predictable is a persons cancer risk? Expert Rev Anticancer Ther 9:389–392

    PubMed  Google Scholar 

  19. Alam AK, Hossain AS, Khan MA, Kabir SR, Reza MA, Rahman MM, Islam MS, Rahaman MAA, Rashid M, Sadik MG (2016) The antioxidative fraction of white mulberry induces apoptosis through regulation of p53 and NFKB in EAC cells. PLoS ONE 11:e0167536

    PubMed  PubMed Central  Google Scholar 

  20. Lü JM, Lin PH, Yao Q, Chen C (2010) Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med 14:840–860

    PubMed  Google Scholar 

  21. Brudner M, Karpel M, Lear C, Chen L, Yantosca LM, Scully C, Sarraju A, Sokolovska A, Zariffard MR, Eisen DP (2013) Lectin dependent enhancement of Ebola virus infection via soluble and transmembrane C type lectin receptors. PLoS ONE 8:e60838

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Kabir SR, Nabi MM, Nurujjaman M, Reza MA, Alam AK, Zaman RU, Khalid BFK, Ruhul MA, Hasan MMK, Hossain MA (2015) Momordica charantia seed lectin: toxicity, bacterial agglutination and antitumor properties. Appl Biochem Biotechnol 175:2616–2628

    CAS  PubMed  Google Scholar 

  23. Rutishauser U, Sachs L (1975) Cell-to-cell binding induced by different lectins. J Cell Biol 65:247–257

    CAS  PubMed  Google Scholar 

  24. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Reed JC (2000) Mechanisms of apoptosis. Am J Pathol 157:1415–1430

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Searle J, Lawson T, Abbott P, Harmon B, Kerr J (1975) An electron microscope study of the mode of cell death induced by cancer chemotherapeutic agents in populations of proliferating normal and neoplastic cells. J Pathol 116:129–138

    CAS  PubMed  Google Scholar 

  27. Balasubramanian A, Ramalingam K, Krishnan S, Ajm C (2005) Anti-inflammatory activity of Morus indica Linn. Iran J Pharmacol Ther 4:13–15

    Google Scholar 

  28. Khalid N, Fawad SA, Ahmed I (2011) Antimicrobial activity, phytochemical profile and trace minerals of black mulberry (Morus nigra L.) fresh juice. Pak J Bot 43:91–96

    CAS  Google Scholar 

  29. Kabir S, Islam F, Jahangir Alom M, Abu Zubair M, Absar N (2012) Purification, characterizations of a snake guard seeds lectin with antitumor activity against Ehrlich ascites carcinoma cells in vivo in mice. Protein Pept Lett 19:360–368

    CAS  PubMed  Google Scholar 

  30. Hasan MM, Islam MS, Hoque KMF, Haque A, Reza MA (2019) Effect of Citrus macroptera fruit pulp juice on alteration of caspase pathway rendering anti-proliferative activity against Ehrlich’s ascites carcinoma in mice. Toxicol Res 35:271–277

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Le VQA, Ahn JY, Heo MY, Cho SJ, Yoon H, Park J, Ko JH, Lee L, Han J, Kim SY (2017) Proteomic profiles of Daphnia magna exposed to lead (II) acetate trihydrate and atrazine. Genes Genomics 39:887–895

    CAS  Google Scholar 

  32. Brand-Williams W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT-Food Sci Technol 28:25–30

    CAS  Google Scholar 

  33. Sur P, Ganguly DK (1994) Tea plant root extract (TRE) as an antineoplastic agent. Planta Med 60:106–109

    CAS  PubMed  Google Scholar 

  34. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005) Cancer statistics, 2005. CA Cancer J Clin 55:10–30

    PubMed  Google Scholar 

  35. Aruoma OI (1998) Free radicals, oxidative stress, and antioxidants in human health and disease. J Am Oil Chem Soc 75:199–212

    CAS  Google Scholar 

  36. Mukherjee PK, Kumar V, Houghton PJ (2007) Screening of Indian medicinal plants for acetylcholinesterase inhibitory activity. Phytother Res 21:1142–1145

    PubMed  Google Scholar 

  37. Lpez-Lzaro M (2010) A new view of carcinogenesis and an alternative approach to cancer therapy. Mol Med 16:144–153

    Google Scholar 

  38. Meyer BN, Ferrigni NR, Putnam JE, Jacobsen LB, Nichols DJ, McLaughlin JL (1982) Brine shrimp: a convenient general bioassay for active plant constituents. Planta Med 45:31–34

    CAS  PubMed  Google Scholar 

  39. Rieser MJ, Gu Z-M, Fang X-P, Zeng L, Wood KV, McLaughlin JL (1996) Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona muricata. J Nat Prod 59:100–108

    CAS  PubMed  Google Scholar 

  40. Jeyaprakash AA, Jayashree G, Mahanta S, Swaminathan C, Sekar K, Surolia A, Vijayan M (2005) Structural basis for the energetics of jacalinsugar interactions: promiscuity versus specificity. J Mol Biol 347:181–188

    Google Scholar 

  41. De Meja EG, Prisecaru VI (2005) Lectins as bioactive plant proteins: a potential in cancer treatment. Crit Rev Food Sci Nutr 45:425–445

    Google Scholar 

  42. Liu B, Bian HJ, Bao JK (2010) Plant lectins: potential antineoplastic drugs from bench to clinic. Cancer Lett 287:1–12

    CAS  PubMed  Google Scholar 

  43. Kabir SR, Zubair MA, Nurujjaman M, Haque MA, Hasan I, Islam MF, Hossain MT, Hossain MA, Alam MT (2011) Purifica- tion and characterization of a Ca2+ dependent novel lectin from Nymphaea nouchali tuber with antiproliferative activities. Biosci Rep 31:465–475

    CAS  PubMed  Google Scholar 

  44. Ahmed H, Chatterjee B, Debnath A (1988) Interaction and in vivo growth inhibition of Ehrlich ascites tumor cells by jacalin. J Biosci 13:419–424

    CAS  Google Scholar 

  45. Jaganathan SK, Mondhe D, Wani Z, Pal HC, Mandal M (2010) Effect of honey and eugenol on Ehrlich ascites and solid carcinoma. Biomed Res Int 2010:989163

    Google Scholar 

  46. Bhattacharyya A, Choudhuri T, Pal S, Chattopadhyay S, Datta GK, Sa G, Das T (2003) Apoptogenic effects of black tea on Ehrlichs ascites carcinoma cell. Carcinogenesis 24:75–80

    CAS  PubMed  Google Scholar 

  47. Islam M, Rahi M, Jahangir CA, Rahman MH, Jerin I, Amin R, Hoque KMF, Reza MA (2018) In vivo anticancer activity of Basella alba leaf and seed extracts against Ehrlich’s ascites carcinoma (EAC) cell line. Evid Based Complement Altern Med 2018:1537896

    Google Scholar 

  48. Hyun JH, Kang JI, Kim SC, Kim E, Kang JH, Kwon JM, Park DB, Lee YJ, Yoo ES, Kang HK (2008) The effects of Crinum asiaticum on the apoptosis induction and the reversal of multidrug resistance in HL-60/MX2. Toxicol Res 24:29–36

    Google Scholar 

  49. Gomes A, Giri B, Alam A, Mukherjee S, Bhattacharjee P, Gomes A (2011) Anticancer activity of a low immunogenic protein toxin (BMP1) from Indian toad (Bufo melanostictus, Schneider) skin extract. Toxicon 58:85–92

    CAS  PubMed  Google Scholar 

  50. Brown JM, Attardi LD (2005) The role of apoptosis in cancer development and treatment response. Nat Rev Cancer 5:231–237

    CAS  PubMed  Google Scholar 

  51. Sa DJ, Lee EJ, Yoo BS (2009) Apoptosis induction by menadione in human promyelocytic leukemia HL-60 cells. Toxicol Res 25:113–118

    CAS  Google Scholar 

  52. Chinni SR, Li Y, Upadhyay S, Koppolu PK, Sarkar FH (2001) Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene 20:2927–2936

    CAS  PubMed  Google Scholar 

  53. Giannakakou P, Robey R, Fojo T, Blagosklonny MV (2001) Low concentrations of paclitaxel induce cell type dependent p53, p21 and G1/G2 arrest instead of mitotic arrest: molecular determinants of paclitaxel- induced cytotoxicity. Oncogene 20:3806–3813

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

All the authors are grateful to Dr. Saidur Rahman (Chief Scientific Officer, Bangladesh Sericulture Research and Training Institute, Rajshahi, Bangladesh) for providing the experimental plant materials.

Funding

There was no significant financial support for this research work.

Author information

Authors and Affiliations

  1. Molecular Biology and Protein Science Laboratory, Department of Genetic Engineering and Biotechnology, Faculty of Life and Earth Science, University of Rajshahi, Rajshahi, 6205, Bangladesh

    Md. Shihabul Islam, Chowdhury Arif Jahangir, Md. Sifat Rahi, Md. Mahmudul Hasan, Salek Ahmed Sajib, Kazi Md. Faisal Hoque & Md Abu Reza

Authors
  1. Md. Shihabul Islam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chowdhury Arif Jahangir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Md. Sifat Rahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Md. Mahmudul Hasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Salek Ahmed Sajib
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kazi Md. Faisal Hoque
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Md Abu Reza
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Md Abu Reza.

Ethics declarations

Conflict of interest

All the authors declared that there are no conflicts of interest about this paper for publication.

Additional information

Md. Shihabul Islam and Chowdhury Arif Jahangir have eqaully contributed and considered as first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Islam, M.S., Jahangir, C.A., Rahi, M.S. et al. In-vivo antiproliferative activity of Morus latifolia leaf and bark extracts against Ehrlich’s ascites carcinoma. Toxicol Res. 36, 79–88 (2020). https://doi.org/10.1007/s43188-019-00011-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43188-019-00011-7

Keywords

Search

Navigation