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Cytotoxic Properties of Methanolic Extracts from Quercus Infectoria and Terminalia Chebula on A549 and PC12 Cancer Cell Lines: A Comparative Study Based on Tannin-rich and Tannin-free content

Articles in Press

Document Type : Original Article

Authors

1 Department of Biochemistry, Fasa University of Medical Sciences, Fasa, Iran

2 Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

3 Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

4 Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

5 Department of Pharmacognosy, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

6 Environmental Health Engineering Department, Faculty of Health, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Background: Quercus infectoria and Terminalia chebula are traditional medicinal plants in the Middle East, known for their significant therapeutic properties. This study aimed to investigate the cytotoxic effects of tannin-rich and tannin-free methanolic extracts, derived from these plants, on A549 (human lung adenocarcinoma) and PC12 (mouse pheochromocytoma) cell lines.
Methods: The extracts were prepared from air-dried plant tissues using a maceration technique. Cytotoxicity was assessed using four different concentrations (1, 10, 50, and 100 µg/mL) using Trypan Blue and WST-1 assays. The half-maximal inhibitory concentrations (IC50) were determined for both cell lines.
Results: The IC50 values revealed that Quercus infectoria exhibited stronger cytotoxic activity compared to T. Chebula. In A549 cells, Quercus infectoria showed IC50 values of 80 µg/mL (tannin-rich) and 102 µg/mL (tannin-free), whereas Terminalia chebula demonstrated 104 µg/mL (tannin-rich) and 111 µg/mL (tannin-free). For PC12 cells, the IC50 values for Quercus infectoria were 68 µg/mL (tannin-rich) and 103 µg/mL (tannin-free), while Terminalia chebula recorded 80 µg/mL (tannin-rich) and 129 µg/mL (tannin-free).  
Conclusion: This study confirms that tannin-rich extracts exhibited greater cytotoxic effects than their tannin-free counterparts, emphasizing the role of tannins in influencing anticancer activity. The findings suggest that tannin-mediated toxicity is a key factor in the observed differences, providing valuable insights into the mechanistic contributions of tannins to cancer cell suppression, which warrants further research into their bioactive mechanisms.

Keywords

Main Subjects

References
  1. Srivastava S, Koay EJ, Borowsky AD, De Marzo AM, Ghosh S, Wagner PD, et al. Cancer overdiagnosis: a biological challenge and clinical dilemma. Nature reviews Cancer. 2019;19(6):349-58. DOI: 1038/s41568-019-0142-8
  2. Feng K, Li X, Bai Y, Zhang D, Tian L. Mechanisms of cancer cell death induction by triptolide: A comprehensive overview. Heliyon. 2024;10(2):e24335. doi: 10.1016/j.heliyon.2024.e24335.
  3. Leng G, Duan B, Liu J, Li S, Zhao W, Wang S, et al. The advancements and prospective developments in anti-tumor targeted therapy. Neoplasia. 2024;56:101024. doi: 10.1016/j.neo.2024.101024.
  4. Chen Q, Chen M, Liu Z. Local biomaterials-assisted cancer immunotherapy to trigger systemic antitumor responses. Chemical Society reviews. 2019;48(22):5506-26. doi: 10.1039/c9cs00271e.
  5. Lu Q-Y, Jin Y-S, Pantuck A, Zhang Z-F, Heber D, Belldegrun A, et al. Green tea extract modulates actin remodeling via Rho activity in an in vitro multistep carcinogenic model. Clinical cancer research. 2005;11(4):1675-83. doi: 10.1158/1078-0432.CCR-04-1608.
  6. Cross SE, Jin Y-S, Lu Q-Y, Rao J, Gimzewski JK. Green tea extract selectively targets nanomechanics of live metastatic cancer cells. Nanotechnology. 2011;22(21):215101. doi: 10.1088/0957-4484/22/21/215101.
  7. Gholamhoseinian A, Shahouzehi B, Mohammadi G. Trace Elements Content of Some Traditional Plants Used for the Treatment of Diabetes Mellitus. BRIAC. 2020;10(5): 6167-73.doi.org/10.33263/BRIAC105.61676173.
  8. Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer letters. 2008;269(2):199-225. doi: 10.1016/j.canlet.2008.03.009.
  9. Macdonald T, Epstein J, Sanderson I. Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies. Br J Nutr. 2010;103(11):1545-57. doi: 10.1017/S0007114509993667.
  10. Ghorbani A, Esmaeilizadeh M. Pharmacological properties of Salvia officinalis and its components. Journal of traditional and complementary medicine. 2017;7(4):433-40. doi: 10.1016/j.jtcme.2016.12.014.
  11. Grzegorczyk-Karolak I, Matkowski A, Wysokińska H. Antioxidant activity of extracts from in vitro cultures of Salvia officinalis L. Food Chemistry. 2007;104:536-41. org/10.1016/j.foodchem.2006.12.003
  12. Russo A, Formisano C, Rigano D, Senatore F, Delfine S, Cardile V, et al. Chemical composition and anticancer activity of essential oils of Mediterranean sage (Salvia officinalis L.) grown in different environmental conditions. Food and Chemical Toxicology. 2013;55:42-7. doi: 10.1016/j.fct.2012.12.036. 
  13. Buyel JF. Plants as sources of natural and recombinant anti-cancer agents. Biotechnology Advances. 2018;36(2):506-20. doi: 10.1016/j.biotechadv.2018.02.002.
  14. Kaur G, Athar M, Alam S. Q. infectoria galls possess antioxidant activity and abrogates oxidative stress-induced functional alterations in murine macrophages. Chem Biol Interact. 2008;171:272-82.. doi: 10.1016/j.cbi.2007.10.002.
  15. Deshpande M, Sk N. Phyto-pharmacological review of chebula Retz. NPAIJ. 2010; 6:24-28.
  16. Jokar A, Masoomi F, Sadeghpour O, Nassiri-Toosi M, Hamedi S. Potential therapeutic applications for T.chebula in Iranian traditional medicine. Journal of Traditional Chinese Medicine. 2016;36(2):250-4. DOI: 1016/s0254-6272(16)30035-8
  17. Prakash DV, Satya N, Sumanjali A, Meena V. Pharmacological review on T.chebula. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2012;3:679-83.
  18. Kim TG, Kang SY, Jung KK, Kang JH, Lee E, Han HM, et al. Antiviral activities of extracts isolated from Terminalis chebula Retz., Sanguisorba officinalis L., Rubus coreanus Miq. and Rheum palmatum L. against hepatitis B virus. Phytother Res. 2001;15(8):718-20. doi: 10.1002/ptr.832.
  19. Hanif A, Ibrahim AH, Ismail S, Al-Rawi SS, Ahmad JN, Hameed M, et al. Cytotoxicity against A549 Human Lung Cancer Cell Line via the Mitochondrial Membrane Potential and Nuclear Condensation Effects of Nepeta paulsenii Briq., a Perennial Herb. Molecules 2023; 28: 2812. doi: 10.3390/molecules28062812.
  20. Kowalczyk T, Merecz-Sadowska A, Rijo P, Mori M, Hatziantoniou S, Górski K, et al. Hidden in Plants—A Review of the Anticancer Potential of the Solanaceae Family in In Vitro and In Vivo Studies. Cancers 2022; 14: 1455. doi: 10.3390/cancers14061455.
  21. Yang J, Cao L, Li Y, Liu H, Zhang M, Ma H. et al. Gracillin Isolated from Reineckia carnea Induces Apoptosis of A549 Cells via the Mitochondrial Pathway. Drug Design, Development and Therapy, 2021; 15: 233–43. DOI:2147/DDDT.S278975
  22. Ginovyan M, Javrushyan H, Hovhannisyan S, Nadiryan E, Sevoyan G, Harutyunyan T, et al. 5‑fluorouracil and Rumex obtusifolius extract combination trigger A549 cancer cell apoptosis: uncovering PI3K/Akt inhibition by in vitro and in silico approaches. Scientific Reports, 2024; 14:14676. doi.org/10.1038/s41598-024-65816-5.
  23. Hostanska K, Jürgenliemk G, Abel G, Nahrstedt A, Saller R. Willow bark extract (BNO1455) and its fractions suppress growth and induce apoptosis in human colon and lung cancer cells. Cancer Detection and Prevention. 2007;31(2):129-39. doi: 10.1016/j.cdp.2007.03.001.
  24. Kong CS, Kim KH, Choi JS, Kim JE, Park C, Jeong JW. Salicin, an Extract from White Willow Bark, Inhibits Angiogenesis by Blocking the ROS‐ERK Pathways. Phytother Res. 2014;28(8):1246-51. doi: 10.1002/ptr.5126.
  25. An H-M, Li G-W, Lin C, Gu C, Jin M, Sun W-X, et al. Acorus tatarinowii Schott extract protects PC12 cells from amyloidinduced neurotoxicity. Die Pharmazie - An International Journal of Pharmaceutical Sciences. 2014;69. PMID: 24855834
  26. Li YF, Gong ZH, Yang M, Zhao YM, Luo ZP. Inhibition of the oligosaccharides extracted from Morinda officinalis, a Chinese traditional herbal medicine, on the corticosterone induced apoptosis in PC12 cells. Life sciences. 2003;72(8):933-42. doi: 10.1016/s0024-3205(02)02331-7.
  27. Gholamhoseinian A, Fallah H, Sharifi-Far F, Mirtajaddini M. Alpha mannosidase inhibitory effect of some Iranian plant extracts. Int J Pharmacol. 2008;4:460-5.
  28. Nyman U, Joshi P, Madsen L, Pedersen T, Pinstrup M, Rajasekharan S, et al. Ethnomedical information and in vitro screening for angiotensin-converting enzyme inhibition of plants utilized as traditional medicines in Gujarat, Rajasthan and Kerala (India). Journal of Ethnopharmacology. 1998;60(3):247-63. doi: 10.1016/s0378-8741(97)00158-x.
  29. de Anta JM, Real FX, Mayol X. Low tumor cell density environment yields survival advantage of tumor cells exposed to MTX in vitro. Biochimica et Biophysica Acta (BBA)-General Subjects. 2005;1721(1-3):98-106. doi: 10.1016/j.bbagen.2004.10.006.
  30. Santos MA, Enyedy EA, Nuti E, Rossello A, Krupenko NI, Krupenko SA. Methotrexate γ-hydroxamate derivatives as potential dual target antitumor drugs. Bioorganic & medicinal chemistry. 15(3):1266-74.  doi: 10.1016/j.bmc.2006.11.017.
  31. Ren J, Fang Z, Yao L, Dahmani FZ, Yin L, Zhou J, et al. A micelle-like structure of poloxamer–methotrexate conjugates as nanocarrier for methotrexate delivery. International journal of pharmaceutics. 2015;487(1-2):177-86. doi: 10.1016/j.ijpharm.2015.04.014. 
  32. Bag A, Bhattacharyya SK, Chattopadhyay RR. The development ofT.chebula Retz. (Combretaceae) in clinical research. Asian Pac J Trop Biomed. 2013;3(3):244-52. doi: 10.1016/S2221-1691(13)60059-3.
  33. Jain M, Chahar P, Jain V, Sharma A, Yadav NR. Role of Quercus infectoria in health and oral health – A review. Int J Green Pharm. 2019;13(3):180–85.
  34. Chung K-T, Wong TY, Wei C-I, Huang Y-W, Lin Y. Tannins and Human Health: A Review. Critical Reviews in Food Science and Nutrition. 1998;38(6):421-64. doi: 10.1080/10408699891274273.
  35. Gao J, Yang X, Yin W, Li M. Gallnuts: A Potential Treasure in Anticancer Drug Discovery. Evid Based Complement Alternat Med. 2018;2018:4930371. doi: 10.1155/2018/4930371.
  36. Rafiquzzaman R. Cytotoxic Effects of Q. Infectoria Extracts towards Cervical (Hela) and Ovarian (Caov-3) Cancer Cell Lines. Health and the Environment Journal. 2010;1(2):17-23.
  37. Saleem A, Husheem M, Härkönen P, Pihlaja K. Inhibition of cancer cell growth by crude extract and the phenolics ofT.chebula Retz. Journal of ethnopharmacology. 2002;81:327-36. doi: 10.1016/s0378-8741(02)00099-5.
  38. Ravi Shankara BE, Ramachandra YL, Rajan SS, Ganapathy PSS, Yarla NS, Richard SA, et al. Evaluating the Anticancer Potential of Ethanolic Gall Extract ofT.chebula (Gaertn.) Retz. (Combretaceae). Pharmacognosy Res. 2016;8(3):209-12. doi: 10.4103/0974-8490.182919.
  39. Wang M, Yang L, Ji M, Zhao P, Sun P, Bai R, et al. Aqueous Extract of T.chebula Induces Apoptosis in Lung Cancer Cells Via a Mechanism Involving Mitochondria-mediated Pathways. Brazilian Archives of Biology and Technology. 2015;58:208-15. org/10.1590/S1516-8913201400202
  40. Ahmad F, Surapaneni KM, Al-Subaie AM, Kamaraj B. Anti-proliferative activity and apoptotic induction of tannins extracted from Quercus infectoria on oral cancer KB cell lines. Journal of Applied Pharmaceutical Science, 2024; 14(06): 184-99. DOI: 7324/JAPS.2024.174009
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Articles in Press, Accepted Manuscript
Available Online from 22 November 2025
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