Cytotoxic effect of Tilia dasystyla and Polygonatum orientale Desf extracts on AGS and SKOV-3 cancer cell lines

Document Type : Research Paper


1 Department of Biotechnology, Faculty of Biological Science, Alzahra University, Tehran , Iran

2 Department of Biomedical Science, Women Research Center, Alzahra University, Tehran, Iran



Nowadays medicinal plants have been considered as the complementary medicine in cancer treatment by researchers. Some plants possess chemical compounds which are able to inhibit the growth of cancer cells or even eliminate them through apoptosis or necrosis. In current study anticancer effect of Tilia dasystyla and Polygonatum orientale Desf extracts on AGS and SKOV-3 cancer cell lines were investigated. The cytotoxic effect of Tilia dasystyla and Polygonatum orientale Desf extracts on AGS and SKOV-3 has not been reported so far. Cancer cell lines were treated with different concentrations (100-5000 µg/ml) of T. dasystyla and P. orientale Desf methanol extracts for 24, 48, 72 hours. Cell viability of AGS and SKOV-3 cancer cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method. Results of the study indicate that, extracts of T. dasystyla and P. orientale Desf showed cytotoxic effect on AGS and SKOV-3 cancer cell lines. The lowest IC50 value of AGS and SKOV-3 cell lines was about 1.02 ± 0.01 mg /ml and 1.14 ± 0.17 mg / ml respectively. T. dasystyla and P. orientale Desf extracts showed cytotoxic effect on AGS and SKOV-3 cancer cell lines in time- and dose-dependent manner. Full potential of the extracts, as an option for cancer treatment, is yet to be determined by further studies on animal models and subsequent trials.


  • Modamio P, Lastra C F, Marino E I. A comparative in vitro study of percutaneous preparations of β-blockers in human skin. J. Pharm. (2000) 194: 249-259.
  • Barry B W. Novel mechanisms and devices to enable successful transdermal drug delivery. J. Pharm. Sci. (2001) 14: 101-114.
  • Shin S-C, Cho C-W. Enhanced transdermal delivery of pranoprofen from the bioadhesive gels. Pharm. Res. (2006) 29: 928-933.
  • Shin S-C, Kim J-Y, Oh I-J. A mucoadhesive and physicochemical characterization of carbopol-poloxamer gels containing triamcinolone acetonide. Drug Dev. Ind. Pharm. (2000) 26: 307-312.
  • Carter S J. Cooper and Gunn’s Tutorial Pharmacy. 6th ed., CBS Publishers; New Delhi (2000).
  • Anand B. Application of organogels in pharmaceuticals. J. Sci. Ind. Res. (2001) 60: 311-318.
  • Beverley J T, Barrie C F. The transdermal revolution. Drug Deliv. Today (2004) 9: 697-703.
  • Cheong-Weon C, Deok-Bae K, Sang-Chul S. Development of bioadhesive transdermal bupivacaine gels for enhanced local anesthetic action. J. Pharm. Res. (2012) 11: 423-431.
  • Hema C, Ajay R, Permender R, Vikash K. Optimization and formulation design of carbopol loaded Piroxicam gel using novel penetration enhancers. J. Bio. Macromol. (2013)55: 246–253.
  • Rachel S H W, Kalliopi D. Effect of drug loading method and drug physicochemical properties on the material and drug release properties of poly (ethylene oxide) hydrogels for transdermal delivery. Polym. (2017) 9: 286.
  • Veeran G K, Guru V B. Water soluble polymers for pharmaceutical applications. (2011) 3: 1972-2009.
  • Anne B, Emer S, and Garret A F G. Analgesic-antipyretic agents; pharmacotherapy of gout. Brunton L L, Lazo J S, Parker K L (Eds.) In: Goodman & Gilman's the pharmacological basis of therapeutics. The McGraw-Hill Companies, Inc. (2006).
  • Moffat A C, Osselton M D, Widdop B, Clarke's Analysis of Drugs and Poisons. 3rd ed., Pharmaceutical Press; London (2004).
  • Ramesh G, Vamshi V Y, Shravan K Y, Chinna R P, Madhusudan R Y. Optimization of Hydrogels for transdermal delivery of lisinopril by Box–Behnken statistical design. AAPS PharmSciTech. (2009) 10: 505-514.
  • Mohammed A, Abdul A, Yasmin S, Asgar A. Status of terpenes as skin penetration enhancers. Drug Discov. Today (2007) 12: 1061-1067.
  • Bharti S, Subheet J, Tiwary A K Percutaneous permeation enhancement by terpenes: Mechanistic view. The AAPS J. (2008) 10:120-132.
  • Weijiang Y, Guohua J, Yang Z, Depeng L, Bin X, Junyi Z Polymer microneedles fabricated from alginate and hyaluronate for transdermal delivery of insulin. Sci. Eng. C (2017) 80: 187–196.
  • Sejal A, Praveen K, Hetal P T. Statistically optimized fast dissolving microneedle transdermal patch of meloxicam: A patient friendly approach to manage arthritis. J. Pharm. Sci. (2017) 104: 114-123.
  • Machekposhtia S A, Soltania M, Najafizadehc P, Ebrahimic S A, Chen P. Biocompatible polymer microneedle for topical/dermal delivery of tranexamic acid. Control. Rel. (2017) 261: 87-92.
  • Wandi et al. A boosting skin vaccination with dissolving microneedle patch encapsulating M2e vaccine broadens the protective efficacy of conventional influenza vaccines. Control. Rel. (2017) 261: 1-9.
  • Fan C, Qinying Y, Yang Y, Mei X W. BCG vaccine powder-laden and dissolvable microneedle arrays for lesion free vaccination. Control. Rel. (2017) 255: 36–44.
  • Ahlam et al. DNA vaccination for cervical cancer; a novel technology platform of RALA mediated gene delivery via polymeric microneedles. : Nanotechnol. Biol Med. (2017) 13: 921–932.
  • Pim et al. Diphtheria toxoid and N-trimethyl chitosan layer-by-layer coated pH-sensitive microneedles induce potent immune responses upon dermalbvaccination in mice. Control. Rel. (2017) 262: 28–36.
  • Jaya A, Sebastien H, Haripriya K, Devin V M, Winston P P, Mark R P. Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects. (2017) 128: 1-7.
  • Anroop B. Synthesis and comparative skin permeability of atenolol and propanolol esters. Drug Deliv. Sci. Tech. (2005) 15: 187-90.
  • Ghosh B, Reddy L. Effect of physicochemical parameters on skin permeability of antihypertensive. Indian J. Exp. Bio. (2001) 39: 710-714.
  • Sera U V, Ramana M V. In vitro skin absorption and drug release -a comparison of four commercial hydrophilic gel preparations for topical use. Pharmacist (2006) 73: 356-360.
  • Loganathan V, Manimaran S, Jaswanth A, Sulaiman A, Reddy M V S, Kumar B S, Rajaseskaran A. The effects of polymers and permeation enhancers on release of Flurbiprofen from gel formulations. J. Pharm. Sci. (2001) 63: 200-204.
  • Chul et al. Effect of sodium chloride on the gelation temperature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium. J. Pharm. (2001) 226: 195-205.
  • Sanjay J B, Padsalg A, Patel K K, Mokale V. Formulation, development and evaluation of fluconazole gel in various polymer bases. Asian J. Pharm. (2007) 1: 63-68.
  • Gupta G, Gaud R. Release rate of Nimesulide from different gellants. Indian J. Pharm. Sci. (1999) 61: 227-230.
  • Gupta G, Gaud R. Release rate of Tenoxicam from acrypol gels. Indian Pharmacist (2005) 17: 69-76.
  • Patel V, Prajapati B, Patel H, Patel K. Mucoadhesive bilayer tablets for Propranolol HCl. AAPS PharmSciTech. (2007) : E1-E6.
  • Roul L K, Manna N K, Parhi R N, Sahoo S, Suresh P. Dissolution rate enhancement of Alprazolam by solid dispersion. Indian J. Pharm. Edu. Res. (2012) 46: 38-44.
  • Wang D, Zhao J, Liu X, Sun F, Zhou Y, Teng L, Li Y. Parenteral thermo-sensitive organogel for schizophrenia therapy, in vitro and in vivo evaluation. J. Pharm. Sci. (2014) 60: 40–44.
  • Takmaz E A, Inal O, Baykara T. Studies on transdermal delivery enhancement of zidovudine. AAPS PharmSciTech. (2009) 10: 88–97.
  • Meera G, Ajay K B. Vehicle influence on permeation through intact and compromised skin. J. Pharm. (2014) 472: 362–368.
  • Parhi R. Development and optimization of pluronic® F127 and HPMC based thermosensitive gel for the skin delivery of metoprolol succinate. Drug Deliv. Sci. Technol. (2016) 36: 23-33.
  • Parhi R, Padilam S. Transdermal delivery of Diltiazem HCl from matrix film: Effect of penetration enhancers and study of antihypertensive activity in rabbit model. J. Adv. Res. (2016) 7: 539–550.
  • Singh H, Ghosh M N. Modified plethysmometer for measuring foot volume of unanaesthetized rats. Pharm. Pharmacol. (1968) 20: 316-317.
  • Bhavesh KL, Hiray RS, Ghongane BB Evaluation of analgesic and anti-inflammatory activity of extract of Holoptelea Integrifolia and Argyreia Speciosa in animal models. Clin. Diagnostic Res. (2015) 9: FF01-FF04.
  • D'Amour F E, Smith D N. A method for determining loss of pain sensation. Pharmacol. Exp. Ther. (1941) 72: 74-79.
  • Jaiswal S R, Sontakke S D. Experimental evaluation of analgesic and anti-inflammatory activity of simvastatin and atorvastatin. Ind. J. Pharmacol. (2012) 44: 475-479.
  • Chaudhary H, Rohilla A, Rathee P, Kumar V Optimization and formulation design of carbopol loaded Piroxicam gel using novel penetration enhancers. Int. J. Biol. Macromol. (2013) 55: 246–253.
  • Sougata J, Sreejan M, Amit K N, Kalyan K S, Sanat K B. Carbopol gel containing chitosan-egg albumin nanoparticles for transdermal aceclofenac delivery. Colloids and Surf. B: Biointerf. (2014) 114: 36–44.
  • Abdul A, Mohd A, Asgar A. Investigation of antihypertensive activity of carbopol valsartan transdermal gel containing 1,8-cineole. J. Biological. Macromol. (2014) 64: 144–149.
  • Raida A-K, Jingyuan W, Angel E-M C, Amy M-J K, Stephanie S M L, Joohee Y. Transdermal delivery of propranolol hydrochloride through chitosan nanoparticles dispersed in mucoadhesive gel. Polym. (2016) 153: 176–186.
  • Williams A C, Barry B W. Penetration enhancers. Drug Deliv. Rev. (2004) 56: 603–618
  • Parhi R, Podilam S, Subasini P. Pluronic lecithin organogel (PLO) of diltiazem hydrochloride: effect of solvents/penetration enhancers on ex vivo permeation. Drug Deliv. Transl. Res. (2016) 6: 243-253.
  • Shubhmita B, Kaushalkumar D, Venkata V K V. Microneedles in the clinic. Control. Rel. (2017) 260: 164–182.
  • Iervolino M, Cappello B, Raghavan S L, Hadgraft J. Penetration enhancement of ibuprofen from supersaturated solutions through human skin. J. Pharm. (2001)212: 131–141.