Bioprospecting the Anticancer Efficacy of Garcinia anomala from North-East India in Ovarian Cancer Cells – An In Vitro Study

Jump To References Section

Authors

  • Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara – 390002, Gujarat ,IN
  • Environmental and Industrial Biotechnology Division, TERI Northeastern Regional Centre, The Energy and Resource Institute, Guwahati – 781036, Assam ,IN
  • Organic Chemistry, ICAR-Directorate of Medicinal and Aromatic Plants Research, Anand – 387310, Gujarat ,IN
  • Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara – 390002, Gujarat ,IN
  • Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara – 390002, Gujarat ,IN
  • Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara – 390002, Gujarat ,IN
  • Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara – 390002, Gujarat ,IN
  • Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara – 390002, Gujarat ,IN

DOI:

https://doi.org/10.18311/jer/2024/34612

Keywords:

Antioxidant, Anticancer, Garcinia, Phytochemicals, Transcript Analysis

Abstract

Background: Ovarian cancer is a type of gynaecological cancer with a worldwide prevalence affecting women aged above 50. Despite several advances made in chemotherapy and surgery, the average time of clinical exemption is approximately two years, and the 5-year survival rate is 45%. But even after survival, they have long-term side effects. So, there is an urgent need for natural anticancer drugs. In this context, Garcinia spp. is one such plant that is explored for its anticancer properties. However, the endemic species Garcinia anomala from North-East India has not been studied for anticancer efficacy. Thereby present study aimed to understand the anticancer efficacy of hexane and methanol extracts of Garcinia anomola short mamilla plant available in the North-East region of India with a major emphasis on antioxidant potential. Further, the best extract with higher antioxidant activity was used to evaluate the anticancer potential through modulation of redox status. Methods: Total phenolic content in extract samples was determined by the Folin-Ciocalteu method. The 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity assay was used to assess the antioxidant activities of extracts. For in vitro evaluation of the anticancer potential of the extract, ovarian teratocarcinoma PA1 cells were used as a model to study the dose-dependent effect of the extract. Various assays, such as wound healing assay and transcriptional analysis of genes, such as Bcl-2, PCNA, and TP53, were performed. For the redox parameter, DCFDA (2’,7’-Dichlorofluoroscin Diacetate) assay was used. Results: The results showed that Garcinia anomola methanol extract (EB) exhibited higher antioxidant activity in comparison to the hexane extract (EA). A cytotoxicity assay was performed to find the effective IC50. From this assay, the effective dose concentration confirmed for EA was 40 µg/mL, EB was 20 µg/mL, and the time point selected was 24 hrs. As the IC50 for EB was less than EA, EB was chosen for further assays. From the wound healing assay, the migration rate obtained was 0.967±0.041 µm/hr. The methanol extract was found to affect key cell cycle checkpoint genes at the transcript level. Conclusion: These results indicate that the anticancer potential is mediated through the modulation of antioxidant status. Thus, Garcinia anomala short mamilla extract from northeast India has good efficacy as an anticancer agent, which can be considered as a future potent drug candidate for ovarian cancer.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Downloads

Published

2024-08-26

How to Cite

Pillai, G., Kar, A., Kumar, S., Shah, Z., Pawar, R., Bhurawala, N., Mahapatra, A., & Nampoothiri, L. (2024). Bioprospecting the Anticancer Efficacy of <i>Garcinia anomala</i> from North-East India in Ovarian Cancer Cells – An <i>In Vitro</i> Study. Journal of Endocrinology and Reproduction, 28(1), 47–57. https://doi.org/10.18311/jer/2024/34612

Issue

Section

Research Article

 

References

Roett MA, Evans P. Ovarian cancer: An overview. Am Fam Physician. 2009; 80(6):609-16.

Monteiro AFM, De O. Viana J, Nayarisseri A, Zondegoumba EN, Mendonça Junior FJB, Scotti MT, et al. Computational studies applied to flavonoids against Alzheimer’s and Parkinson’s diseases. Oxid Med Cell Longev. 2018; 2018:1-21. https://doi.org/10.1155/2018/7912765 PMid:30693065 PMCid:PMC6332933

Jhofi M, Husni E, Hamidi D. Anticancer and antioxidant activity of Asam Kandis (Garcinia cowa Roxb.) leaf extract and fraction. 2nd International Conference on Contemporary Science and Clinical Pharmacy 2021 (ICCSCP 2021) 2021 Nov 17. Atlantis Press; 2021. p. 214-221. https://doi.org/10.2991/ahsr.k.211105.032

US Preventive Services Task Force. Screening for ovarian cancer. JAMA. 2018; 319(6):588-94. https://doi.org/10.1001/jama.2017.21926 PMid:29450531

Smith RA, Andrews K, Brooks D, DeSantis CE, Fedewa SA, Lortet-Tieulent J, et al. Cancer screening in the United States, 2016: A review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin. 2016; 66(2):95-114. https://doi.org/10.3322/caac.21336 PMid:26797525

Volpe J, Filipi JG, Cooper OR, Penson RT. Frontline therapy of ovarian cancer: Trials and tribulations. Curr Opin Obstet Gynecol. 2018; 30(1):1-6. https://doi.org/10.1097/GCO.0000000000000434 PMid:29251676

Ambarwati NS, Elya BE, Malik AM, Hanafi M. Phytochemical and antimicrobial studies on Garcinia lattissima Miq. fruit extract. Asian J Pharm Clin Res. 2017; 10(7):230-2. https://doi.org/10.22159/ajpcr.2017.v10i7.18528

Zelenak C, Pasham V, Jilani K, Tripodi PM, Rosaclerio L, Pathare G, et al. Tanshinone IIA stimulates erythrocyte phosphatidylserine exposure. Cell Physiol Biochem. 2012; 30(1):282-94. https://doi.org/10.1159/000339064 PMid:22759974

Mackeen MM, Ali AM, Lajis NH, Kawazu K, Kikuzaki H, Nakatani N. Antifungal garcinia acid esters from the fruits of Garcinia atroviridis. Z Naturforsch C. 2002; 57(3-4):291-5. https://doi.org/10.1515/znc-2002-3-416 PMid:12064729

Panthong K, Hutadilok-Towatana N, Panthong A. Cowaxanthone F. A new tetraoxygenated xanthone, and other anti-inflammatory and antioxidant compounds from Garcinia cowa. Can J Chem. 2009; 87(11):1636-40. https://doi.org/10.1139/V09-123

Balasubramanyam K, Altaf M, Varier RA, et al. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J BiolChem. 2004; 279(32):33716-26. https://doi.org/10.1074/jbc.M402839200 PMid:15155757

Qiao Y, Xu Y, Liu X, et al. Microwave assisted antibacterial action of Garcinia nanoparticles on gram-negative bacteria. Nat Commun. 2022; 13(1):2461. https://doi.org/10.1038/s41467-022-30125-w PMid:35513402 PMCid:PMC9072325

Muhammad Y, Kani YA, Iliya S, et al. Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria. SAGE Open Med. 2021; 9:2050312121991246. https://doi.org/10.1177/2050312121991246 PMid:33614035 PMCid:PMC7871282

Yamaguchi F, Saito M, Ariga T, et al. Free radical scavenging activity and antiulcer activity of garcinol from Garcinia indica fruit rind. J Agric Food Chem. 2000; 48(6):2320-5. https://doi.org/10.1021/jf990908c PMid:10888544

Sang S, Pan MH, Cheng X, et al. Chemical studies on antioxidant mechanism of garcinol: Analysis of radical reaction products of garcinol and their antitumor activities. Tetrahedron. 2001; 57(50):9931-8. https://doi.org/10.1016/S0040-4020(01)01015-8

Sang S, Pan MH, Cheng X, et al. Chemical studies on antioxidant mechanism of garcinol: Analysis of radical reaction products of garcinol and their antitumor activities. Tetrahedron. 2001; 57(50):9931-8. https://doi.org/10.1016/S0040-4020(01)01015-8

Fonmboh DJ, Abah ER, Fokunang TE, et al. An overview of methods of extraction, isolation and characterization of natural medicinal plant products in improved traditional medicine research. Asian J Res Med Pharm Sci. 2020; 9(2):31-57. https://doi.org/10.9734/ajrimps/2020/v9i230152

Kalita P, Tapan BK, Pal TK, Kalita R. Estimation of Total Flavonoids Content (TFC) and antioxidant activities of methanolic whole plant extract of Biophytum sensitivum Linn. J Drug Deliv Ther. 2013; 3(4):33-7. https://doi.org/10.22270/jddt.v3i4.546

Vani T, Rajani M, Sarkar S, Shishoo CJ. Antioxidant properties of the ayurvedic formulation triphala and its constituents. Int J Pharmacogn. 1997; 35(5):313-7. https://doi.org/10.1080/09251619708951274

Sánchez‐Moreno C, Larrauri JA, Saura‐Calixto F. Free radical scavenging capacity of selected red, rose and white wines. J Sci Food Agric. 1999; 79(10):1301-4. https://doi.org/10.1002/(SICI)1097-0010(19990715)79:10<1301::AID-JSFA367>3.3.CO;2-P

Navarro MC, Montilla MP, Cabo MM, et al. Antibacterial, antiprotozoal and antioxidant activity of five plants used in Izabal for infectious diseases. Phytother Res. 2003; 17(4):325-9. https://doi.org/10.1002/ptr.1134 PMid:12722133

Pramanik A, Laha D, Dash SK, et al. An in-vivo study for targeted delivery of copper-organic complex to breast cancer using chitosan polymer nanoparticles. Mater Sci Eng C. 2016; 68:327-37. https://doi.org/10.1016/j.msec.2016.05.014 PMid:27524027

Laha D, Pramanik A, Chattopadhyay S, et al. Folic acid modified copper oxide nanoparticles for targeted delivery in in vitro and in vivo systems. RSC Adv. 2015; 5(83):68169-78. https://doi.org/10.1039/C5RA08110F

Wahyuni FS, Byrne LT, Dianita R, et al. A new ring-reduced tetraprenyltoluquinone and a prenylated xanthone from Garcinia cowa. Aust J Chem. 2004; 57(3):223-6. https://doi.org/10.1002/chin.200431179

Khan MA, Rahman AA, Islam S, et al. A comparative study on the antioxidant activity of methanolic extracts from different parts of Morus alba L. (Moraceae). BMC Res Notes. 2013; 6:1-9. https://doi.org/10.1186/1756-0500-6-24 PMid:23331970 PMCid:PMC3559264

Cheok CY, Chin NL, Yusof YA, Law CL. Extraction of total phenolic content from Garcinia mangostana Linn. Hull. I. Effects of solvents and UV-vis spectrophotometer absorbance method. Food Bioprocess Tech. 2012; 5:2928-33. https://doi.org/10.1007/s11947-011-0627-2

Parthsarathy U, Nandakishore OP. A study on nutrient and medicinal compositions of selected Indian Garcinia species. Curr Bioact Compd. 2014; 10(1):55-61. https://doi.org/10.2174/157340721001140725001152

Ambarwati NS, Elya BE, Malik AM, Hanafi M. Phytochemical and antimicrobial studies on Garcinia lattissima Miq. fruit extract. Asian J Pharm Clin Res. 2017; 10(7):230-2. https://doi.org/10.22159/ajpcr.2017.v10i7.18528

Karimi E, Jaafar HZ, Ahmad S. Phenolics and flavonoids profiling and antioxidant activity of three varieties of Malaysian indigenous medicinal herb Labisia pumila Benth. J Med Plant Res. 2011; 5:1200-6.

Kim DO, Jeong SW, Lee CY. Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chem. 2003; 81(3):321-6. https://doi.org/10.1016/S0308-8146(02)00423-5

Kim KC, Lee C. Curcumin induces downregulation of E2F4 expression and apoptotic cell death in HCT116 human colon cancer cells; involvement of reactive oxygen species. Korean J Physiol Pharmacol. 2010; 14(6):391. https://doi.org/10.4196/kjpp.2010.14.6.391 PMid:21311680 PMCid:PMC3034119

Woo JH, Kim YH, Choi YJ, et al. Molecular mechanisms of curcumin-induced cytotoxicity: Induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-X L and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis. 2003; 24(7):1199-208. https://doi.org/10.1093/carcin/bgg082 PMid:12807727

Kumar S, Chattopadhyay SK, Darokar MP, et al. Cytotoxic activities of xanthochymol and isoxanthochymol substantiated by LC-MS/MS. Planta Med. 2007; 73(14):1452-6. https://doi.org/10.1055/s-2007-990255 PMid:17999352

Paunesku T, Mittal S, Protić M, et al. Proliferating Cell Nuclear Antigen (PCNA): Ringmaster of the genome. Int J Radiat Biol. 2001; 77(10):1007-21. https://doi.org/10.1080/09553000110069335 PMid:11682006

Levine AJ. p53, the cellular gatekeeper for growth and division. Cell. 1997; 88(3):323-31. https://doi.org/10.1016/S0092-8674(00)81871-1 PMid:9039259

Kirkin V, Joos S, Zörnig M. The role of Bcl-2 family members in tumorigenesis. Biochim Biophys Acta-Mol Cell Res. 2004; 1644(2-3):229-49. https://doi.org/10.1016/j.bbamcr.2003.08.009 PMid:14996506

Paul S, Mandal SK, Bhattacharyya SS, et al. In vitro and in vivo studies demonstrate anticancer property of root extract of Polygala senega. Journal Acupunct Meridian Stud. 2010; 3(3):188-96. https://doi.org/10.1016/S2005-2901(10)60035-0 PMid:20869020

Subapriya R, Kumaraguruparan R, Nagini S. Expression of PCNA, cytokeratin, Bcl-2 and p53 during chemoprevention of hamster buccal pouch carcinogenesis by ethanolic neem (Azadirachta indica) leaf extract. Clin Biochem. 2006; 39(11):1080-7. https://doi.org/10.1016/j.clinbiochem.2006.06.013 PMid:16989797

Grigalius I, Petrikaite V. Relationship between antioxidant and anticancer activity of trihydroxyflavones. Molecules. 2017; 22(12):2169. https://doi.org/10.3390/molecules22122169 PMid:29215574 PMCid:PMC6149854

Katsube N, Iwashita K, Tsushida T, et al. Induction of apoptosis in cancer cells by bilberry (Vaccinium myrtillus) and the anthocyanins. J Agric Food Chem. 2003; 51(1):68-75. https://doi.org/10.1021/jf025781x PMid:12502387

Ross HA, McDougall GJ, Stewart D. Antiproliferative activity is predominantly associated with ellagitannins in raspberry extracts. Phytochemistry. 2007; 68(2):218-28 https://doi.org/10.1016/j.phytochem.2006.10.014 PMid:17126865

Al-Dabbagh B, Elhaty IA, Al Hrout AA, et al. Antioxidant and anticancer activities of Trigonella foenum-graecum, Cassia acutifolia and Rhazya stricta. BMC Compl Altern Med. 2018; 18(1):1-2. https://doi.org/10.1186/s12906-018-2285-7 PMid:30134897 PMCid:PMC6103858

Ainsworth EA, Gillespie KM. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent. Nat Protoc. 2007; 2(4):875-7. https://doi.org/10.1038/nprot.2007.102 PMid:17446889

Mondal SK, Saha P, Mondal NB, Mazumder UK. Free radical scavenging property of Annona reticulata leaves. Orient Pharm Exp Med. 2008; 8(3):260-5. https://doi.org/10.3742/OPEM.2008.8.3.260