IN VIVO ANTITUMOR ACTIVITY OF PHYTOCHEMICAL PITC-2 OBTAINED FROM TISSUE CULTURED PLANT PLUCHEA INDICA ON SARCOMA-180 SOLID TUMOR MICE MODEL


Soumita Goswami, Souvik Debnath, Saumen Karan, Tapan Kumar Chatterjee

Abstract


 Objective: PITC-2 was isolated from the methanolic root extract of tissue cultured medicinal plant Pluchea indica (L.) Less. PITC-2 is a thiophene derivative which is 2-(Prop-1-ynyl)-5(5,6-dihydroxyhexa-1,3-diynyl)-thiophene. The main objective of the study is to evaluate the in vivo antitumor activity of PITC 2 against sarcoma-180 cancer cell in Swiss albino mice.

Methods: The antitumor activity was evaluated by treatment with PITC-2 at a dose of 2.5 and 5 mg/kg b.w for 21 days on sarcoma-180 mice model. Cell viability was studied using 3-(4, 5- dimethylthiazol -2-yl)-2, 5-diphenyl tetrazolium bromide assay and cell apoptosis, G1 cell cycle arrest and reduction in tumor cell proliferation were evaluated by histopathological analysis and Bcl-2, cyclic-D1, and Ki-67 protein expression through immunohistochemistry study.

Results: Precisely, PITC-2 had a cytotoxic effect on various in vitro cancer cells. Significant decreases in solid tumor volume and weight along with increase lifespan also observed. The histopathological and immunohistopathological examination indicates that PITC-2 induces apoptosis, typical morphological changes and suppresses tumor cell proliferation along with G1 cell cycle arrest through the downregulation of the intratumoral expression of Bcl-2, cyclic D1, and Ki-67 and thus highlighting antiproliferative and apoptotic properties against sarcoma-180 in vivo solid tumor model.

Conclusion: The present results clearly demonstrate that PITC-2 significantly inhibits sarcoma-180 cell growth in a dose-dependent manner in in vivo mice model. Besides this, the study reveals a comprehensive perception of the possible mechanism behind the antitumor activity of PITC-2 by significant changes in the morphological, hematological, biochemical parameters in sarcoma-180 cells.


Keywords


Apoptosis, Cell viability, PITC-2, Sarcoma-180, Antitumor activity, Cell proliferation.

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References


Bissell MJ, Radisky D. Putting tumours in context. Nat Rev Cancer 2001;1:46-54.

Fattah AA, Darwish HA, Fathy N, Shouman SA. Carbition anhydrase inhibition boost the antitumor effect of imatinib mesylate via potentiating the antiangiogenic and antimetastatic machineries. Toxicol Appl Pharmacol 2017;316:123-38.

Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ, et al. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43-66.

Hussein BH, Azab HA. A novel antitumor agent Ln(lll) 2-thioacetate benzothiazole induces anti-angiogenic effect and cell death in cancer cell lines. Eur J Med Chem 2012;51:99-109.

American Cancer Society. Global Cancer Facts and Figure. 3rd ed. Atlanta: American Cancer Society; 2015. p. 1-61.

Skommer J, Brittain T, Raichoudhuri S. Bcl-2 inhibits apoptosis by increasing time-to-death and intrinsic cell-to-cell variations in the mitochondrial pathway of cell death. Apoptosis 2010;15:1223-33.

Swanton E, Savory P, Cosulich S, Woodman P. Bcl-2 regulates caspase 3/caspase 2 apoptotic cascade in cytosolic extracts. Oncogene 1999;18:1781-7.

Nygren P, Larsson R. Overview of the clinical efficacy of investigational anticancer drugs. J Intern Med 2003;253:46-75.

Nozlena SA, Ahmed AB, Rasedee A, Tengku IA, Rahman H, Keong SY. Zerumbone (ZER) induces apoptosis in HEPG2 cells via mitochondrial pathway. Int J Pharm Pharm Sci 2015;7:298-302.

Harborne JB. Arsenal for survival: Secondary plant products. Taxon 2000;49:435-49.

Pramanik KC, Biswas R, Mitra A, Bandyopadhyay D, Mishra M, Chatterjee TK. Tissue culture of the plant Pluchea indica (L.) Less. and evaluation of diuretic potential of its leaves. Orient Pharm Exp Med 2007;7:197-204.

Chakraborty S, Chatterjee TK. Targeting viseral leishmaniasis by mannosylated liposome incorporated PITC-2 isolated from the plant Pluchea indica (L) Less. Int J Pharm Bio Sci 2017;8:396-408.

Biswas R, Dutta PK, Achari B, Bandyopadhyay D, Mishra M, Pramanik KC, et al. Isolation of pure compound R/J/3 from Pluchea indica (L.) less. And its anti-amoebic activities against entamoeba histolytica. Phytomedicine 2007;14:534-7.

Mutiah R, Sukardiman, Widyawaruyanti A. Cytotoxic effect of crude exteact and fraction from Calotropis gigantea leaves on human colon cancer widr cell lines. Int J Pharm Pharm Sci 2017;9:83-6.

Sinha A, Banerjee K, Banerjee A, Das S, Choudhuri SK. Synthesis characterisation and biological evaluation of a noble vanadium complex as a possible anticancer agent. J Organi Chem 2014;772-773:34-41.

Joseph MM, Aravind SR, George SK, Pillai KR, Mini S, Sreelekha TT, et al. Antitumor activity of galactoxyloglucan-gold nanoparticles against murine ascites and solid carcinoma. Colloids Surf B Biointerfaces 2014;116:219-27.

Pal A, Bhattacharya I, Bhattacharya K, Mandal C, Ray M. Methylglyoxal induced activation of murine peritoneal macrophages and surface markers of T lymphocytes in sarcoma-180 bearing mice: Involvement of MAP kinase, NF-kappa beta signal transduction pathway. Mol Immunol 2009;46:2039-44.

Nascimento FR, Cruz GV, Pereira PV, Silva MC. Ascitic and solid Ehrlich tumor ingibition by Chenopodium ambrosiodes L. treatment. Cell Immunol 2006;78:2650-3.

Chakraborty A, Talukday D, Pal A, Ray M. Immunomodulation of macrophages by methyl glyoxal conjugated with chitosan nanoparticles against sarcoma-180 tumor in mice. Cell Immunol 2014;287:27-35.

Bala A, Kar B, Halder PK, Bera S. Evaluation of anticancer activity of Cleome gynandra on ehrlich’s ascitec carcenoma treated mice. J Ethnopharmacol 2010;129:131-4.

Gaballah HH, Gaber RA, Mohamed DA. Apigenin potentiates the antitumor activity of 5-FU on solid ehrlick carcinoma: Crosstalk between apoptotic and JNK mediated autophagic cell death platforms. Toxicol Appl Pharmacol 2017;316:27-35.

de Costa PM, de Costa MP, Jamacaru VF, Ferreira PM. Inprovement of in vivo anticancer and antiangiogenic potential of thalidomide derivatives. Chem Biol Interact 2015;239:174-83.

Gupta M, Mazumder UK, Kumar RS, Kumar TS. Antitumor activity and antioxidant role of bauhinia racemosa against ehrlich ascites carcinoma in swiss albino mice. Acta Pharmacol Sin 2004;25:1070-6.

Elsherbiny NM, Younis NN, Elseweids MM. The synergistic effect between vanillin and doxorubicin in ehrlich ascites carcinoma solid tumor and MCF-7 human brest cancer cell line. Pathol Res Pract 2016;212:767-77.

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A, et al. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.

Debnath S, Karan S, Debnath M, Chatterjee TK. Poly-L-Lysine inhibits tumor angiogenesis and induces apoptosis in ehrlich ascites carcinoma and sarcoma S-180 tumor. Asian Pac J Cancer Prev 2017;18:2255-68.

de Sousa AP, Torres MR, Pessoa C, Lotufo LV. In vivo growth-inhibition of sarcoma 180 tumor by alginates from brown seaweed Sargassum vulgare. Carbohydr Polym 2007;69:7-13.

Govindarasu M, Palani M, Vaiyapuri M. In ailico docking study on kaempferitrin with diverse inflammatory and apoptotic proteins functional approach towards the colon cancer. Int J Pharm Pharm Sci 201;9:199-204.

Paul S, Kundu R. Induction of apoptosis by fatty acid rich fraction of Solanum nigrum on carvical cancer cell lines. Int J Pharm Pharm Sci 2017;9:199-206.

de Silva Faria MC, dos Santos NAG, Rodrigues MA, dos Santos AC. Effect of diabetes on biodistribution, nephrotoxicity and antitumor activity of cicplatin in mice. Chem Biol Interact 2015;229:119-31.

Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki67. J Immunol 1984;133:1710-15.

Diehl JA. Cycling to cancer with cyclic D1. Cancer Biol Ther 2002;3(1):226-31.

Baldin V, Lukas J, Marcote MJ, Pagano M, Draette G. Cyclic D1 is a nuclear protein requires for cell cycle progression in G1. Genes Dev 1993;7:812-21.




About this article

Title

IN VIVO ANTITUMOR ACTIVITY OF PHYTOCHEMICAL PITC-2 OBTAINED FROM TISSUE CULTURED PLANT PLUCHEA INDICA ON SARCOMA-180 SOLID TUMOR MICE MODEL

Topics

Pharmaceutical Technology, Pharmacology

Keywords

Apoptosis, Cell viability, PITC-2, Sarcoma-180, Antitumor activity, Cell proliferation.

DOI

10.22159/ajpcr.2018.v11i4.23968

Date

01-04-2018

Additional Links

Manuscript Submission

Journal

Asian Journal of Pharmaceutical and Clinical Research
Vol 11 Issue 4 April 2018 Page: 211-218

Print ISSN

0974-2441

Online ISSN

2455-3891

Statistics

82 Views | 96 Downloads

Authors & Affiliations

Soumita Goswami
Pharmacology Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata - 700 032, West Bengal, India.
India

Souvik Debnath
Pharmacology Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata - 700 032, West Bengal, India.
India

Saumen Karan
Pharmacology Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata - 700 032, West Bengal, India.
India

Tapan Kumar Chatterjee
Pharmacology Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata - 700 032, West Bengal, India.
India


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