Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2016 | Research article

Pro-apoptotic and cytotoxic effects of enriched fraction of Elytranthe parasitica (L.) Danser against HepG2 Hepatocellular carcinoma

Authors: Nimmy Kumar, Subhankar Biswas, Asha Elizabeth Mathew, Subin Varghese, Jessy Elizabeth Mathew, K. Nandakumar, Jesil Mathew Aranjani, Richard Lobo

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

Login to get access

Abstract

Background

Hepatocellular carcinoma (HCC), the most common type of liver cancer accounts for more than one million deaths worldwide. Current treatment modality for HCC is marginally effective. Plants belonging to Mistletoe family (Loranthaceae) have been used in chemotherapy for many years. The present study was aimed at exploring the anti-proliferative, pro-oxidant and pro-apoptotic potential of stem of Elytranthe parasitica (L.) Danser (EP), a parasitic shrub belonging to Loranthaceae.

Methods

Elytranthe parasitica (L.) Danser, a climbing parasitic shrub was investigated for its cytotoxic activity against HepG2, a hepatocellular carcinoma cell line by Sulforhodamine B (SRB) assay. Further, pro-oxidant activity of EP extract/fractions was studied using copper phenanthroline assay. To understand the mechanism of cell death, the pro-apoptotic effects of Hep-G2 cells treated with EP extract/fractions were visualized by dual staining using acridine orange and ethidium bromide, a morphological marker of apoptosis. Phytochemical profiling of EP was explored by estimating the phenol, flavonoid and tannin content in its various fractions and extract. The occurrence of gallic acid, a principal polyphenol in EP extract and fractions was detected and further quantified using HPTLC (High Performance Thin Layer Chromatography) fingerprinting.

Result

Active fraction of Elytranthe parasitica, EP.DEE exhibited potent cytotoxic activity in a dose dependent manner against HepG2 hepatocellular carcinoma cell line with an IC50 of 56.7 ± 7.8 μg/mL. Dual staining with acridine orange and ethidium bromide revealed that HepG2 cells treated with EP active fractions underwent cell death chiefly by apoptosis. Highest phenol, flavonoid and tannin content were observed in active fractions, EP.EA (Ethyl acetate fraction) and EP.DEE (Diethyl ether fraction). Gallic acid was identified and quantified in EP extract and active fractions, EP.DEE and EP.EA.

Conclusion

Our findings indicate EP active fraction could be a promising contender in the treatment of hepatocellular carcinoma.
Literature
1.
2.
3.
EASL–EORTC Clinical Practice Guideline. Management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.CrossRef
4.
5.
Cabibbo G, Enea M, Attanasio M, Bruix J, Craxı A, Camm C. A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma. Hepatology. 2010;51(4):1274–83.CrossRefPubMed
6.
7.
8.
9.
Liu BL, Zhang X, Zhang W, et al. New enlightenment of French Paradox: resveratrol's potential for cancer chemoprevention and anti-cancer therapy. Cancer Biol Ther. 2007;6:1833–6.CrossRefPubMed
10.
Ding M, Feng R, Wang SY, et al. Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. J Biol Chem. 2006;281:17359–68.CrossRefPubMed
11.
Bhat GK. Flora of Udupi. Udupi, India: Indian Naturalist; 2003. p. 548–9.
12.
Narasimhachar SG. Latin and Kannada names of indigenous and medicinal plants of mysore. Mysore, India: Government Press; 1969.
13.
Zhengyi W, Raven P, Deyuan H. Flora of China. St Louis, USA: Missouri Botanical Garden; 2003. p. 220–39.
14.
Anderson LA, Philipson JD. Mistletoe – the magic herb. The Pharm J. 1982;229:437–9.
15.
16.
Kienle GS, Glockmann A, Schink M, Kiene H. Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research. J Exp Clin Can Res. 2009;28:79–112.CrossRef
17.
Büssing A. Immune modulation using mistletoe (Viscum album L.) extracts Iscador. Arzneimittelforschung. 2006;56(6A):508–15.PubMed
18.
Melzer J, Iten F, Hostanka K, Saller R. Efficacy and safety of mistletoe preparations (Viscum album) for patients with cancer diseases. Forsch Komplementmed. 2009;16:217–26.CrossRefPubMed
19.
Devehat FL, Bakthiar A, Bezivin C, Amoros M, Boustie J. Antiviral and cytotoxic activities of some Indonesian plants. Fitoterapia. 2002;73:400–5.CrossRef
20.
Hermawan A, Murwanti R, Artanti N, Meiyanto E, et al. Effect of the water extract of Macrosolen cochinchinensis (Lour.) Tiegh. leaves on 7,12-dimethylbenz-antracene induced female mice liver carcinogensis. J Chin Pharm Sci. 2011;20(6):627–32.CrossRef
21.
Sodde V, Dashora N, Prabhu K, Lobo R. Evaluation of anticancer activity of Macrosolen parasiticus (L.) Danser Stem on Ehrlich’s Ascites Carcinoma treated mice. Int J Can Res. 2011;7(2):135–43.CrossRef
22.
Sodde V, Lobo R, Kumar N, Maheshwari R, Shreedhara CS. Cytotoxic activity of macrosolen parasiticus (L.) Danser on the growth of breast cancer cell line (MCF-7). Pharmacog Mag. 2015;11 Suppl 1:S156–60. doi:10.​4103/​0973-1296.​157719.
23.
Houghton P, Raman A. Laboratory Handbook for the fractionation of crude extracts. US: Springer; 1998. p. 54–65.CrossRef
24.
Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc. 2006;1(3):1112–6.CrossRefPubMed
25.
Dorman D, Hiltunen R. Antioxidant and pro-oxidant in vitro evaluation of water soluble food related botanical extracts. Food Chem. 2011;129:1612–8.CrossRef
26.
Aruoma OI, Murcia A, Butler J, Halliwell B. Evaluation of the anti-oxidant and pro-oxidant actions of gallic acid and its derivatives. J Agri Food Chem. 1993;141:1880–5.CrossRef
27.
Liu K, Liu P, Liu R, Wu X. Dual AO/EB staining to detect apoptosis in Osteosarcoma cells compared with Flow cytometry. Med Sci Monit Basis Res. 2015;21:15–20.CrossRef
28.
29.
Evans WC, Evans D. Trease and evans pharmacognosy. Philadelphia: Saunders Ltd; 2009.
30.
Sawant L, Pandita N, Prabhakar B. Determination of gallic acid in phyllanthus emblica linn. dried powder by HPTLC. J Pharm Bioallied Sci. 2010;2(2):105–8.CrossRefPubMedPubMedCentral
31.
Adesegun SA, Fajana A, Orabueze CI, Coker HAB. Evaluation of anti-oxidant properties of phaulopsis fascisepala C.B.C.I. (Acanthaceae). Evid Based Compl Alt Med. 2009;6(2):227–31.CrossRef
32.
Chang CC, Yang M-H, Wen H-M, Chern J-C. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J Food Drug Anal. 2002;10(3):178–82.
33.
Bubba MD, Giordani E, Pippucci L, Cincinelli A, Checchini L, Galvan P. Changes in tannins, ascorbic acid and sugar content in astringent persimmons during on-tree growth and ripening and in response to different postharvest treatments. J Food Compos Anal. 2009;22:668–77.CrossRef
34.
Houghton P, Fang R, Techatanawat I, Steventon G, Hylands PJ, Lee CC. The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity. Methods. 2007;42:377–87.CrossRefPubMed
35.
36.
Sun G, Zhang S, Xie Y, Zhang Z, Zhao W. Gallic acid as a selective anticancer agent that induces apoptosis in SMMC-7721 human hepatocellular carcinoma cells. Oncol Lett. 2016;11:150–8.PubMed
37.
Newell A, Yousef G, Lila M, Ramirez-Mares M, Mejia E. Comparative in vitro bioactivities of tea extracts from six species of Ardisia and their effect on growth inhibition of HepG2 cells. J Ethnopharmacol. 2010;130:536–44.CrossRefPubMed
38.
Babich H, Schuck AG, Weisburg JH, Zuckerbraun HL. Research strategies in the study of the pro-oxidant nature of polyphenol nutraceuticals. J Toxicol. 2011; doi:10.​1155/​2011/​467305
39.
Aruoma OI, Evans PJ, Kaur H, Sutcliffe L, Halliwell B. Evaluation of the antioxidant and potential pro-oxidant properties of food additives and of Trolox C, vitamin E and probucol. Free Rad Res Commun. 1990;10:143–57.CrossRef
40.
Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J. Vitamin C exhibits pro-oxidant properties. Nature. 1998;392–559.
41.
Schumacker PT. Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell. 2006;10:175–6.CrossRefPubMed
42.
Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev. 2011;8:579–91. doi:10.​1038/​nrd2803.
43.
Pervaiz S, Clement MV. Tumor intracellular redox status and drug resistance — serendipity or a causal relationship? Curr Pharm Des. 2004;10:1969–77.CrossRefPubMed
44.
Magda D, Miller RA. Motexafin gadolinium: a novel redox active drug for cancer therapy. Semin Cancer Biol. 2006;16:466–76.CrossRefPubMed
45.
Maeda H, et al. Effective treatment of advanced solid tumors by the combination of arsenic trioxide and L-buthionine-sulfoximine. Cell Death Differ. 2004;11:737–46.CrossRefPubMed
46.
Hannun Y. Apoptosis and the dilemma of cancer chemotherapy. J Am Soc Hematol. 1997;89(6):1845–53.
47.
Xiao J, Huang G, Zhu C, Ren D, Zhang S. Morphological study on apoptosis HeLa cell induced by soyasaponins. Toxicol In Vitro. 2007;21:820–6.CrossRefPubMed
48.
Frankfurt OS, Krishnan A. Apoptosis based drug screening and detection of selective toxicity to cancer cells. Anticancer Drugs. 2003;14:555–61.CrossRefPubMed
49.
Liu HR. Potential synergy of phytochemicals in cancer prevention. J Nutr. 2004;135(12):3479S–84S.
50.
Li T, Zhang X, Zhao X. Powerful protective effects of gallic acid and tea polyphenols on human hepatocytes injury induced by hydrogen peroxide or carbon tetrachloride in vitro. J Med Plant Res. 2010;4(3):247–54.
51.
Inoue M, Suzuki R, Sakaguchi N, Li Z, Takeda T, Ogihara Y, Jiang BY, Chen Y. Selective induction of cell death in cancer cells by gallic acid. Biol Pharm Bull. 1995;18(11):1526–30.CrossRefPubMed
52.
Apak R, et al. Novel pro-oxidant activity assay for polyphenols, vitamins C and E using a modified CUPRAC method. Talanta. 2013;115:583–9.CrossRefPubMed
Metadata
Title
Pro-apoptotic and cytotoxic effects of enriched fraction of Elytranthe parasitica (L.) Danser against HepG2 Hepatocellular carcinoma
Authors
Nimmy Kumar
Subhankar Biswas
Asha Elizabeth Mathew
Subin Varghese
Jessy Elizabeth Mathew
K. Nandakumar
Jesil Mathew Aranjani
Richard Lobo
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1395-3

Other articles of this Issue 1/2016

BMC Complementary Medicine and Therapies 1/2016 Go to the issue

Research article

Antimalarial properties of crude extracts of seeds of Brucea antidysenterica and leaves of Ocimum lamiifolium

Research article

Acupuncture for insomnia after stroke: a systematic review and meta-analysis

Research article

Exploring self-use, attitude and interest to study complementary and alternative medicine (CAM) among final year undergraduate medical, pharmacy and nursing students in Sierra Leone: a comparative study

Research article

Anti-fatigue effect of Amarkand on endurance exercise capacity in rats

Research article

Celastrus orbiculatus extract inhibits the migration and invasion of human glioblastoma cells in vitro

Research article

Chemical profiling, antimicrobial and insecticidal evaluations of Polygonum hydropiper L