DOI QR코드

DOI QR Code

Quantitative Assessment of the Relative Antineoplastic Potential of the n-butanolic Leaf Extract of Annona Muricata Linn. in Normal and immortalized Human Cell Lines

  • George, V. Cijo (School of Bio Sciences and Technology, VIT University) ;
  • Kumar, D.R. Naveen (School of Bio Sciences and Technology, VIT University) ;
  • Rajkumar, V. (School of Bio Sciences and Technology, VIT University) ;
  • Suresh, P.K. (School of Bio Sciences and Technology, VIT University) ;
  • Kumar, R. Ashok (Department of Zoology, Government Arts College)
  • Published : 2012.02.29

Abstract

Natural products have been the target for cancer therapy for several years but there is still a dearth of information on potent compounds that may protect normal cells and selectively destroy cancerous cells. The present study was aimed to evaluate the cytotoxic potential of n-butanolic leaf extract of $Annona$ $muricata$ L. on WRL-68 (normal human hepatic cells), MDA-MB-435S (human breast carcinoma cells) and HaCaT (human immortalized keratinocyte cells) lines by XTT assay. Prior to cytotoxicity testing, the extract was subjected to phytochemical screening for detecting the presence of compounds with therapeutic potential. Their relative antioxidant properties were evaluated using the reducing power and $DPPH^*$radical scavenging assay. Since most of the observed chemo-preventive potential invariably correlated with the amount of total phenolics present in the extract, their levels were quantified and identified by HPLC analysis. Correlation studies indicated a strong and significant (P<0.05) positive correlation of phenolic compounds with free radical scavenging potential. The results revealed that the extract was moderately cytotoxic to normal cells with a mean IC50 value of 52.4 ${\mu}g$ when compared with those obtained for cancerous cells (IC50 values of 29.2 ${\mu}g$ for MDA-MB-435S and 30.1 ${\mu}g$ for HaCaT respectively). The study confirms the presence of therapeutically active antineoplastic compounds in the n-butanolic leaf extract of $Annona$ $muricata$. Isolation of the active metabolites from the extract is in prospect.

Keywords

References

  1. Baskar R, Rajeswari V, Kumar TS (2007). In vitro antioxidant studies in leaves of Annona species. Indian J Exp Biol, 45, 480-5.
  2. Bekro YA, Jana A, Mamyrbekova B, et al (2007). Etude ethnobotanique et screening phytochimique de Caesalpina benthamiana (Bail) Herend et Zarucchi (Caesalpiniaceae). Science Nature, 4, 217-25.
  3. Borris RP (1996). Natural product research. Perspective from a major Pharmaceutical company. J Ethnopharmacol, 51, 29-38. https://doi.org/10.1016/0378-8741(95)01347-4
  4. Chabner, Roberts (2005). Timeline: Chemotherapy and the war on cancer. Nat Rev Cancer, 5, 65-72. https://doi.org/10.1038/nrc1529
  5. Dohou N, Yamni K, Tahrouch S, et al (2003). Screening phytochimique dune endemique Libero- Marocaine, Thymelaea luthroides. Bull Pharm Bordeau, 142, 61-8.
  6. Fortunato E A, McElroy A K, Sanchez I, et al (2000). Exploitation of cellular signaling and regulatory pathways by human cytomegalovirus. Trends Microbiol, 8, 111-9. https://doi.org/10.1016/S0966-842X(00)01699-1
  7. Gali-Muhtasib H, Bakkar N (2002). Modulating cell cycle: current applications and future prospects for future drug development. Curr. Cancer Drug Targets, 2, 1-17. https://doi.org/10.2174/1568009023334015
  8. Gouemo NP, Yasuda RP, Morad M, et al (2003). Audiogenic seizure alters the expression of calcium and potassium channel protein in inferior colliculus neurons of the genetically epilepsy-prone rat (GEPR-3). Abs Soc Neurosci Program, ?, 212-20.
  9. Gulcin I, Oktay M, Kirecci E, et al (2003). Screening of antioxidant and antimicrobial activities of anise (Pimpinella anisum L.) seed extracts. Food Chem, 83, 371-82. https://doi.org/10.1016/S0308-8146(03)00098-0
  10. Hansakul P, Ngamkitidechakul C, Ingkaninan K, et al (2009). Antiproliferative, apoptotic induction, and antiinvasive effects of Leersia hexandra (L.) Sw, Panicum repens Linn, and Brachiaria mutica (Forsk.) Stapf extracts on human cancer cells. J Sci Technol, 31, 79-84.
  11. Hill AF (1952). Economic Botany. A textbook of useful plants and plant products. 2nd edn. McGarw-Hill Book Company Inc, New York.
  12. Koleva, Van Beek TA, Linssen JPH, et al (2002). Screening of plant extracts for antioxidant activity: a comparative study on three testing methods. Phytochemical Analysis, 13, 8-17. https://doi.org/10.1002/pca.611
  13. Liaw CC, Change FR, Lin CY, et al (2002). New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata. J Nat Prod, 65, 470-5. https://doi.org/10.1021/np0105578
  14. Lister E, Wilson P (2001). Measurement of total phenolics and ABTS assay for antioxidant activity (personal communication). Crop Research Institute, Lincoln, New Zealand.
  15. Magadula JJ, Innocent E, Otiewo JN (2009). Mosquito larvicidal and cytotoxic activities of 3 Annona species and isolation of active principles. J Med Plants Res, 3, 674-80.
  16. Nagamine MK, da Silva TC, Matsuzaki P, et al (2009). Cytotoxic effects of butanolic extract from Pfaffia paniculata (Brazilian Ginseng) on cultured human breast cancer cell line MCF-7. Experimental and toxicologic pathology, 61, 75-82. https://doi.org/10.1016/j.etp.2008.01.017
  17. Pardhasaradhi BV, Reddy M, Ali AM, et al (2005). Differential cytotoxic effects of Annona squamosa seed extracts on human tumour cell lines: Role of reactive oxygen species and glutathione. J Biosci, 30, 237-44. https://doi.org/10.1007/BF02703704
  18. Polterait O (1997). Antioxidants and free-radical scavengers of Natural Origin. Current Org. Chem, 1, 415-40.
  19. Powis G (1983). Dose-dependent metabolism, therapeutic effect, and toxicity of anticancer drugs in man. Drug Metab Rev, 14, 1145-63. https://doi.org/10.3109/03602538308991425
  20. Sakakibara H, Honda Y, Nakagawa S, et al (2003). Simultaneous determination of all polyphenols in vegetables, fruits, and teas. J of Agricultural and Food Chemistry, 51, 571-81. https://doi.org/10.1021/jf020926l
  21. Sameer Mehndiratta, Sunil Kumar, Ajay Kumar Meena, et al (2011). A Review on Plants a useful source of anti-cancer drugs. J of Pharmacy Research, 4, 264-71.
  22. Shalini, Rachana Srivastava (2009). Antifungal activity screening and hplc analysis of crude extract from tectona grandis, shilajit, valeriana wallachi. EJEAFChe, 8, 218-29.
  23. Siddhuraju P, Mohan PS, Becker K (2002). Studies on the antioxidant activity of Indian Laburnum (Cassia fistula L.): a preliminary assessment of crude extracts from stem bark, leaves, flowers and fruit pulp. Food Chem, 79, 61-7. https://doi.org/10.1016/S0308-8146(02)00179-6
  24. Suresh Kumar, Suresh PK, Vijaybabu MR, et al (2006). Anticancer effects of ethanolic neem extract on prostate cancer cell line (PC-3). J of Ethnopharmacology, 105, 246-50. https://doi.org/10.1016/j.jep.2005.11.006
  25. Thatte U, Bagadey S, Dahanukar S (2000). Modulation of programmed cell death by medicinal plants. Molecular and cellular Biochemistry, 46, 199-214.
  26. Velioglu YS, Mazza G, Gao L, et al (1998). Antioxidant activity and total phenolics in selected fruits, vegetables, and grain products. J of Agricultural and Food Chemistry, 46, 4113-7. https://doi.org/10.1021/jf9801973
  27. Weislow R, Kiser DL, Fine J, et al (1989). New soluble-formazan assay for HIV-1 cytopathic effects: application to high-flux screening of synthetic and natural products for AIDSantiviral activity. J Natl Cancer Inst, 81, 577-86. https://doi.org/10.1093/jnci/81.8.577
  28. Ye F, Shen Z, Xie M (2002). Alpha glucosidase inhibition from a Chinese medicinal herb (Ramulus mori) in normal and diabetic rats and mice. Phytomedicine, 9, 161-6. https://doi.org/10.1078/0944-7113-00065
  29. Yen GC, Duh PD, Tsai CL (1993). Relationship between antioxidant activity and maturity of peanut hulls. J Agr Food Chem, 41, 67-70. https://doi.org/10.1021/jf00025a015
  30. Yildirim A, Mavi, Kara AA (2001). Determination of antioxidant and antimicrobial activities of Rumes crispus L. extracts. J Agr. Food Chem, 49, 4083-9. https://doi.org/10.1021/jf0103572
  31. Yu L, Haley S, Perret J, et al (2002). Free radical scavenging properties of wheat extracts. J of Agricultural and Food Chemistry, 50, 1619-24. https://doi.org/10.1021/jf010964p
  32. Yuan SS, Chang HL, Chen HW, et al (2003). Annonacin, a monotetrahydrofuran acetogenin, arrests cancer cells at the G1 phase and causes cytotoxicity in a Baxand caspase-3-related pathway. Life Sciences, 72, 2853-61. https://doi.org/10.1016/S0024-3205(03)00190-5

Cited by

  1. Apoptosis-Induced Cell Death due to Oleanolic Acid in HaCaT Keratinocyte Cells -a Proof-of-Principle Approach for Chemopreventive Drug Development vol.13, pp.5, 2012, https://doi.org/10.7314/APJCP.2012.13.5.2015
  2. Comparative Studies to Evaluate Relative in vitro Potency of Luteolin in Inducing Cell Cycle Arrest and Apoptosis in HaCaT and A375 Cells vol.14, pp.2, 2013, https://doi.org/10.7314/APJCP.2013.14.2.631
  3. The Chemopotential Effect of Annona muricata Leaves against Azoxymethane-Induced Colonic Aberrant Crypt Foci in Rats and the Apoptotic Effect of Acetogenin Annomuricin E in HT-29 Cells: A Bioassay-Guided Approach vol.10, pp.4, 2015, https://doi.org/10.1371/journal.pone.0122288
  4. on the Prostate, BPH-1 Cells, and Some Target Genes vol.14, pp.1, 2015, https://doi.org/10.1177/1534735414550198
  5. Antioxidant, DNA protective efficacy and HPLC analysis of Annona muricata (soursop) extracts vol.52, pp.4, 2015, https://doi.org/10.1007/s13197-014-1289-7
  6. Anti-cancer effect of Annona Muricata Linn Leaves Crude Extract (AMCE) on breast cancer cell line vol.16, pp.1, 2016, https://doi.org/10.1186/s12906-016-1290-y
  7. Herbal remedies and functional foods used by cancer patients attending specialty oncology clinics in Trinidad vol.16, pp.1, 2016, https://doi.org/10.1186/s12906-016-1380-x
  8. (Graviola) Leaf Extract via Activation of Mitogen-Activated Protein Kinase Pathways in RAW 264.7 Macrophages vol.2016, pp.1741-4288, 2016, https://doi.org/10.1155/2016/2905127
  9. L. Seeds vol.2016, pp.2090-9071, 2016, https://doi.org/10.1155/2016/6948098
  10. Bioefficacy of Graviola leaf extracts in scavenging free radicals and upregulating antioxidant genes vol.7, pp.2, 2016, https://doi.org/10.1039/C5FO01258A
  11. A Review of Black Salve: Cancer Specificity, Cure, and Cosmesis vol.2017, pp.1741-4288, 2017, https://doi.org/10.1155/2017/9184034
  12. (Soursop) vol.5, pp.5, 2017, https://doi.org/10.1002/fsn3.498
  13. leaves and their influence on genomic stability vol.80, pp.23-24, 2017, https://doi.org/10.1080/15287394.2017.1377653
  14. Linn. (Annonaceae) Fruit Extract in Rodents vol.17, pp.12, 2014, https://doi.org/10.1089/jmf.2013.0088
  15. Annona muricata (Annonaceae): A Review of Its Traditional Uses, Isolated Acetogenins and Biological Activities vol.16, pp.7, 2015, https://doi.org/10.3390/ijms160715625
  16. L.) as potent source of natural antioxidants for stabilization of palm olein during accelerated storage vol.4, pp.6, 2016, https://doi.org/10.1002/fsn3.349
  17. ): A Comprehensive Mechanistic Review vol.2018, pp.1942-0994, 2018, https://doi.org/10.1155/2018/1826170
  18. Exploring the Leaves of Annona muricata L. as a Source of Potential Anti-inflammatory and Anticancer Agents vol.9, pp.1663-9812, 2018, https://doi.org/10.3389/fphar.2018.00661
  19. Thermal characterization and microbiology assay of Annona muricata L. leaves pp.1588-2926, 2019, https://doi.org/10.1007/s10973-019-08050-w