• P-ISSN 0974-6846 E-ISSN 0974-5645

Indian Journal of Science and Technology

Article

Indian Journal of Science and Technology

Year: 2023, Volume: 16, Issue: Special Issue 1, Pages: 75-88

Original Article

Methanolic Extract of Mallotus roxburghianus Muell. Exhibit Anti-Cancer Activity against Dalton’s Lymphoma Ascites (DLA) bearing Mice via Alterations of Apoptotic Genes E xpression and Redox-Homeostasis

Received Date:23 January 2023, Accepted Date:09 June 2023, Published Date:06 September 2023

Abstract

Objectives: The current study examined the anti-cancer effects of methanolic extract of Mallotus roxburghianus (MRME) using Dalton’s Lymphoma Ascites (DLA) bearing mice. Methods: According to OECD guidelines, the acute toxicity of MRME was assessed, and the LD50 of MRME was estimated using probit analysis. The effects of MRME on survival time, weight change, and antioxidant/oxidant status were determined in DLA mice by administering the animals with different doses of MRME, and doxorubicin was used as a standard reference drug. Cytotoxicity, activities of serum enzymes, and haematological parameters were also determined after treatment with MRME. Effects of MRME on DNA damage and the differential gene expression of apoptotic genes were also studied using Comet assay and qPCR techniques respectively. Findings: MRME significantly reduced tumour growth and extended the survival duration of tumour-bearing mice with increased in MST (26.0  0.72), AST (23.0  0.60), % IMLS (79.3  0.58) and % IALS (50.0  0.91) after treatment with 150 mg/kg. MRME also decreased antioxidant activities and enhanced lipid peroxidation. Decreased RBC levels and haemoglobin content in DLA mice were significantly reversed by MRME treatment. MRME also reduces AST, ALT, LDH, and CRE levels, which were otherwise increased in the DLA control animals. The apoptosis-based anti-cancer effects of M. roxburghianus were revealed by the induction of DNA damage, up-regulation of pro-apoptotic genes, and down-regulation of anti-apoptotic genes in DLA mice after M. roxburghianus treatment. MRME treatment increased the relative expressions of pro-apoptotic genes such as Apaf1, p53 and Bax by 3.19, 3.81 and6.06 folds, respectively when compared to untreated control. Novelty: Our study demonstrates the anti-cancer activities of the methanolic extract of M. roxburghianus leaves thus potentiating the use of the plant for further development of anti-cancer agents.

Keywords: Mallotus roxburghianus; Dalton’s Lymphoma Ascites; Anticancer; DNA damage; Apoptotic genes

References

  1. Zosangzuali M, Lalremruati M, Lalmuansangi C, Nghakliana F, Z. Pharmacological Importance and Chemical Composition of Mallotus roxburghianus Müell. Arg. In: Phytochemistry and Pharmacology of Medicinal Plants. (pp. 1-15) Apple Academic Press, Inc.. 2022.
  2. Anh NH, Park S, Trang DT, Yen DTH, Tai BH, Yen PH, et al. Genus mallotus (euphorbiaceae): a review on traditional medicinal use, phytochemistry and biological activities. Vietnam Journal of Science and Technology. 2022;60(2):141–174. Available from: https://doi.org/10.15625/2525-2518/16634
  3. Cancer facts sheet. World health organization . Available from: https://www.who.int/news-room/fact-sheets/detail/cancer
  4. Mohan L. Plant-Based Drugs as an Adjuvant to Cancer Chemotherapy. In: Akram M., ed. Alternative Medicine. IntechOpen. 2020.
  5. Prasathkumar M, Anisha S, Dhrisya C, Becky R, Sadhasivam S. Therapeutic and pharmacological efficacy of selective Indian medicinal plants – A review. Phytomedicine Plus. 2021;1(2):1–28. Available from: https://doi.org/10.1016/j.phyplu.2021.100029
  6. Elekofehinti OO, Iwaloye O, Olawale F, Ariyo EO. Saponins in Cancer Treatment: Current Progress and Future Prospects. Pathophysiology. 2021;28(2):250–272. Available from: https://doi.org/10.3390/pathophysiology28020017
  7. Khan T, Ali M, Khan A, Nisar P, Jan SA, Afridi S, et al. Anticancer Plants: A Review of the Active Phytochemicals, Applications in Animal Models, and Regulatory Aspects. Biomolecules. 2020;10(1):1–30. Available from: https://doi.org/10.3390/biom10010047
  8. Lalremruati M, Lalmuansangi C, Zosangzuali M, Tochhawng L, Trivedi AK, Kumar NS, et al. Mussaenda macrophylla Wall. exhibit anticancer activity against Dalton’s lymphoma ascites (DLA) bearing mice via alterations of redox-homeostasis and apoptotic genes expression. The Journal of Basic and Applied Zoology. 2022;83(6):1–14. Available from: https://doi.org/10.1186/s41936-022-00268-9
  9. Zosangzuali M, Pachuau L, Pau KS, Zothansiama. Effects of low-dose irradiation on chromosomal damage and oxidative stress in cultured human peripheral blood. Journal of Environmental Biology. 2020;41:908–914. Available from: http://dx.doi.org/10.22438/jeb/4(SI)/MS_1915
  10. Arfin S, Jha NK, Jha SK, Kesari KK, Ruokolainen J, Roychoudhury S, et al. Oxidative Stress in Cancer Cell Metabolism. Antioxidants. 2021;10(5):1–28. Available from: https://doi.org/10.3390/antiox10050642
  11. Aggarwal V, Tuli HS, Varol A, Thakral F, Yerer MB, Sak K, et al. Role of Reactive Oxygen Species in Cancer Progression: Molecular Mechanisms and Recent Advancements. Biomolecules. 2019;9(11):1–26. Available from: https://doi.org/10.3390/biom9110735
  12. Kim SJ, Kim HS, Seo YR. Understanding of ROS-Inducing Strategy in Anticancer Therapy. Oxidative Medicine and Cellular Longevity. 2019;2019:1–13. Available from: https://doi.org/10.1155/2019/5381692
  13. He H, Wang L, Qiao Y, Zhou Q, Li H, Chen S, et al. Doxorubicin Induces Endotheliotoxicity and Mitochondrial Dysfunction via ROS/eNOS/NO Pathway. Frontiers in Pharmacology. 2019;10(1531):1–16. Available from: https://doi.org/10.3389/fphar.2019.01531
  14. Kennedy L, Sandhu JK, Harper MEE, Cuperlovic-Culf M. Role of Glutathione in Cancer: From Mechanisms to Therapies. Biomolecules. 2020;10(10):1–28. Available from: https://doi.org/10.3390/biom10101429
  15. Iuchi K, Takai T, Hisatomi H. Cell Death via Lipid Peroxidation and Protein Aggregation Diseases. Biology. 2021;10(5):1–19. Available from: https://doi.org/10.3390/biology10050399
  16. Wang TH, Tseng WC, Leu YL, Chen CY, Lee WC, Chi YC, et al. The flavonoid corylin exhibits lifespan extension properties in mouse. Nature Communications. 2022;13(1238):1–16. Available from: https://doi.org/10.1038/s41467-022-28908-2
  17. Kapoor I, Bodo J, Hill BT, Hsi ED, Almasan A. Targeting BCL-2 in B-cell malignancies and overcoming therapeutic resistance. Cell Death & Disease. 2020;11(941):1–11. Available from: https://doi.org/10.1038/s41419-020-03144-y
  18. Afroze N, Pramodh S, Shafarin J, Bajbouj K, Hamad M, Sundaram MK, et al. Fisetin Deters Cell Proliferation, Induces Apoptosis, Alleviates Oxidative Stress and Inflammation in Human Cancer Cells, HeLa. International Journal of Molecular Sciences. 2022;23(3):1–20. Available from: https://doi.org/10.3390%2Fijms23031707
  19. Alam M, Ali S, Mohammad T, Hasan GM, Yadav DK, Hassan MI. B Cell Lymphoma 2: A Potential Therapeutic Target for Cancer Therapy. International Journal of Molecular Sciences. 2021;22(19):1–21. Available from: https://doi.org/10.3390/ijms221910442
  20. Carneiro BA, El-Deiry WS. Targeting apoptosis in cancer therapy. Nature Reviews Clinical Oncology. 2020;17:395–417. Available from: https://doi.org/10.1038/s41571-020-0341-y

Copyright

© 2023 Zosangzuali et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Published By Indian Society for Education and Environment (iSee)

DON'T MISS OUT!

Subscribe now for latest articles and news.