PHYTOCHEMICAL PROFILING AND ANTICANCER ACTIVITY OF DRAGON FRUIT HYLOCEREUS UNDATUS EXTRACTS AGAINST HUMAN HEPATOCELLULAR CARCINOMA CANCER (HEPG-2) CELLSHTML Full Text
PHYTOCHEMICAL PROFILING AND ANTICANCER ACTIVITY OF DRAGON FRUIT HYLOCEREUS UNDATUS EXTRACTS AGAINST HUMAN HEPATOCELLULAR CARCINOMA CANCER (HEPG-2) CELLS
K. Padmavathy, K. Sivakumari *, S. Karthika, S. Rajesh and K. Ashok
Department of Zoology, Presidency College, Chennai - 600005, Tamil Nadu, India.
ABSTRACT: To investigate the phytoconstituents and anticancer potential followed by apoptotic studies of H. undatus fruit extracts on HepG-2 cells. Qualitative phytochemical profiling and anti-proliferation activity of Aqueous, Chloroform, Ethyl acetate, Hexane, and Methanol extracts of dragon fruit pulp was carried out. Based on the results of anti-proliferation studies, methanol extract was taken further for apoptotic study by treating HepG-2 cells for nuclear staining using DAPI and GC-MS analysis to elucidate the presence of active compounds. Qualitative phytochemical analysis revealed the presence of carbohydrates, tannins, saponins, anthocyanin, quinones, cardiac glycosides, terpenoids, triterpenoids, phenols, acids, and steroids in aqueous fruit extract. Similarly, chloroform fruit extract showed the presence of carbohydrates, saponins, alkaloids, cardiac glycosides, triterpenoids, phenols, and coumarins. Likewise, Ethyl acetate fruit extract had carbohydrates, tannins, saponins, flavonoids, alkaloids, anthocyanin, cardiac glycosides, terpenoids, triterpenoids, acids, and steroids. In hexane fruit extract, carbohydrate, saponins, anthocyanin, quinones, phenols, and acids were present. But more phytocompouds such as carbohydrates, tannins, saponins, flavonoids, alkaloids, anthocyanin, cardiac glycosides, terpenoids, triterpenoids, phenols, acids, and steroids were found in methanol fruit extract. A dose-dependent anti-proliferative assay revealed that the IC50 value was 112.43 µg/ml in aqueous extract, 99.13 µg/ml in chloroform extract, 102.68 µg/ml in ethyl acetate extract, 83.96 µg/ml in hexane extract, and 69.09 µg/ml in methanol extract at 24 h incubation. Methanol fruit extract of H. undatus showed intense fragments of a nucleus as signs of apoptosis by DAPI staining. GC-MS results revealed that 43 aromatic compounds are present in methanol extract, which may have polyphenolic compounds. This study in-toto pragmatically shows that methanol extracts of H. undatus have demonstrated promising anticancer properties against human liver cancer (HepG-2) cells.
Dragon fruit, Phytochemicals, HepG-2, MTT, DAPI, GC-MS
INTRODUCTION: Cancer is a major public health problem, with significant associated death and disability. It is the second leading cause of death in developed countries 1, 2. Cancer is considered a human tragedy, and the causality prevalence resulting from cancer is increasing.
WHO has predicted that by 2020, that the number of cancer new cases will reach 15 million 3. Cancers that arise in any other part of the body, such as lung, colon, or breast, and spread to the liver is called metastatic cancer rather than liver cancer 4.
Liver cancer is the second most common cause of cancer death, accounting for more than 7,00,000 deaths every year. Hepatocellular carcinoma (HCC) is the major type of liver cancer (70%-80%), followed by intrahepatic cholangio-carcinoma 5-11. The main risk factors for liver cancer are hepatitis B/hepatitis C virus infection, alcohol consumption, aflatoxin B1, and metabolic disorders 12. Herbal drugs include plants, herbal complexes and herbal products or plant or even a combination of plants which were used thousand years before inventing modern drugs 13. Herbal treasure options or complementary alternative medicine (CAM) offers a host of new phytochemicals that could be helpful as a preventive and clinical in managing the liver associated imbalance involving HCC. Several food items, as well as herbs that we use in our every-day life, could be protective agents against liver cancer. Studies have shown that traditional medicines could delay tumour progression, increase survival, and improve the quality of life due to synergis-tically efficient chemotherapy / radiotherapy 14.
Dragon fruit is an important source of phyto-chemicals such as polyphenols, flavonoids, and vitamin C, which are related to its antioxidant activity 15, 16. The red and white dragon fruits especially have recently drawn growing attention worldwide not only because of their economic values, but also for their health benefits 17. Red dragon fruit consumption was reported to decrease total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels while increasing the high-density lipoprotein cholesterol (HDL-C) level in type 2 diabetic 18. Though both red and white dragon fruits are reported to be a rich, natural and cost-effective source of bioactive nutrients, few studies focused on the beneficial effects of white dragon fruit on diabetes and NAFLD (Non-alchoholic Fatty Liver Disease) 19. Therefore, the present investigation was aimed to explore the phytoconstituents present in various pulp extracts of dragon fruit, H. undatus, and its anti-proliferative effect against human hepatocellular carcinoma (HepG-2) cell.
MATERIALS AND METHODS:
Collection and Identification: Dragon fruits, Hylocereus undatus were collected from Koyambedu fruit market, Chennai, Tamil Nadu, India. The fruit was identified and authenticated as per morphological characteristics by Prof. P. Jayaraman, Institute of Herbal Botany, Plant Anatomy Research Centre, West Tambaram, Chennai, Tamil Nadu, India (PARC/2017/3377).
Cancer Cell Line and Chemicals: Cancer cell line HepG-2 (Human Hepatocellular Carcinoma cell) was purchased from National Centre for Cell Science (NCCS) Pune, India. Dulbecco’s Modified Eagle Medium (DMEM), Trypsin- EDTA, Fetal Bovine Serum (FBS), 3-(4,5- Dimethyl thiazol-2yl)-2,5-dimethyl tetrazolium bromide (MTT), Dimethyl Sulphoxide (DMSO), Sodium bicar-bonate, Propidium Iodide, Acridine Orange, Ethidium Bromide and Antibiotic solution were purchased from Sigma, Lout., USA. Likewise, 96 well plates, 6 well plates, tissue culture flasks (25 mm2 and 75 mm2), 15 ml and 50 ml centrifuge tubes were purchased from Hi-Media, USA. Chemicals used in the present study were extra pure and highest analytical grade.
Preparation of Fruit Extracts:
Aqueous Extraction: The outer epicarp of the fruit was separated, and the endocarp was shade-dried. Exactly 20 g of dried endocarp was crushed to powder by maceration method using a kitchen blender. A suspension of 5% (w/v) was prepared in a flask by adding hot boiled distilled water to the fruit powder and kept in a shaker at 200 rpm for 4 h at 37ºC. Then, the suspension was brought to room temperature, filtered through four layers of No.1 Whatman filter paper, and finally passed through a 0.22 µm filter. The filtered aqueous extract was freeze-dried, and the powder was stored at -20 ºC until further use. For cell culture studies, 10 g of the freeze-dried powder was taken and dissolved in DMSO 10.
Chloroform, Ethyl Acetate, Hexane and Methanol Extraction: The dried endocarp powder (20 g) was taken, and a suspension of 5% (w/v) was prepared in a separate flask by soaking the fruit powder in chloroform, ethyl acetate, hexane, and methanol.
They were kept in 4 h on a shaker, filtered, and evaporated at room temperature in petri-dishes. The dried material was retrieved and stored in tubes at -20ºC until further experimental uses. The chloroform, ethyl acetate, hexane, and methanol extracts were dissolved in DMSO to prepare (10 mg/ml) stock solution for cell culture studies 10.
Preliminary Phytochemical Screening: All five fruit extracts were subjected to preliminary phytochemical screening for their phytoconstituents according to Kokate (1988) method.
The powdered extracts were dissolved in acetone and used for further phytochemical studies 20.
Anti-Proliferative Activity (MTT Assay): The anti-poliferative effect of all the five extracts of H. undatus against HepG-2 cancer cells was assessed by the MTT (3-(4, 5- dimethylthiazol-2yl)-2, 5-diphenyltetrazolium) method as described by Mosmann (1983) 21.
Nuclear Staining (DAPI Staining Method): Nuclear staining by using DAPI stain and viewing the apoptotic morphology of the HepG-2 cells under a fluorescence microscope, containing appropriate DAPI stain filters followed by the method of Jang et al. (2002) 22.
GC-MS Analysis (Gas-Chromatography and Mass Spectroscopy): Best anticancer activity was observed in methanol fruit extract when compared to other extracts of H. undatus, and hence the phytoconstituents of methanol fruit extract with its structure was assessed by GC-MS chromatogram.
The filtrate was analyzed for secondary metabolites by using GC MATE II GC-MS (Agilent). For this, 1.0 μl of the compound was injected through HP-5 capillary column, maintained at 220◦C, and helium was used as carrier gas at a flow rate of 1.0 ml/min. After analysis, the compound was identified by matching with the structural library.
Statistical Analysis: The data of MTT assay with five replicates were subjected to statistical analysis, and the mean value along with its respective standard error was calculated. The per cent change between control and experimental value was calculated. The data were analyzed statistically using ‘Two Way Analysis of Variance (ANOVA)’. The data together with tables and graphs/bar diagrams are presented in appropriate places in text 10.
Yield of Extracts: The powder of fruit pulp of H. undatus is highly soluble in distilled water, chloroform, ethyl acetate, hexane, and methanol. All the fruit extracts of H. undatus resembled a dark brown coloured paste.
Preliminary Phytochemical Screening: In our study, the analysis of phytoconstituents of H. undatus showed the presence of carbohydrate, tannins, saponins, anthocyanin, quinones, cardiac glycosides, terpenoids, triterpenoids, phenols, acids, and steroids in aqueous extract, carbo-hydrate, saponins, alkaloids, cardiac glycosides, triterpenoids, phenols and coumarins in chloroform extract, carbohydrate, tannins, saponins, flavonoids, alkaloids, anthocyanin, cardiac glycosides, terpenoids, triterpenoids, acids, steroids in ethyl acetate, carbohydrate, saponins, anthocyanin, quinones, phenols, and acids in hexane extract, carbohydrate, tannins, saponins, flavonoids, alkaloids, anthocyanin, cardiac glycol-sides, terpenoids, triterpenoids, phenols, acids and steroids in methanol extract Table 1.
TABLE 1: PHYTOCHEMICAL SCREENING OF VARIOUS FRUIT EXTRACTS OF H. UNDATUS
|S. no.||Secondary Metabolites||Aqueous||Chloroform||Ethyl Acetate||Hexane||Methanol|
+++ = Strongly present ++ = slightly present + = Present in trace amount - = absent.
Anticancer Activity: In our study, anti-proli-feration of the cells was assessed by MTT assay for 24 h in all the fruit pulp extracts of H. undatus, and the data are presented in Table 2 and Fig. 1.
The data revealed that anticabcer activity was seen in the HepG-2 cells when treated with different concentrations (25, 50, 75, and 100) of various fruit pulp extracts; the cell anti-proliferation being directly proportional to concentration. Per cent cell viability of HepG-2 cells was assessed for 24 h in all the fruit pulp extracts at varying concentrations. The control cells were 100% viable, and the viability decreased significantly with an increase in the concentration of the extracts. The per cent decrease in cell viability was indirectly proportional to the concentration of H. undatus pulp extracts.
Statistical treatment of the data by two-way ANOVA showed that all the values were significant at 5% level.
TABLE 2: PER CENT CELL VIABILITY OF HepG-2 CELLS WHEN TREATED WITH VARIOUS FRUIT EXTRACTS OF H. UNDATUS AT 24 H EXPOSURE
|25 µg/ml||93.07 ± 0.06*
|91.59 ± 1.19*
|89.02 ± 0.61*
|81.30 ± 1.34*
|79.46 ± 0.41*
|50 µg/ml||82.07 ± 0.06*
|78.67 ± 0.72*
|77.90 ± 0.28*
|61.34 ± 0.04*
|62.72 ± 0.88*
|75 µg/ml||71.02 ± 0.48*
|64.09 ± 0.79*
|62.33 ± 0.27*
|55.19 ± 1.29*
|46.06 ± 2.16*
|100 µg/ml||56.98 ± 0.43*
|49.50 ± 0.95*
|51.29 ± 0.38*
|40.71 ± 0.61*
|24.89 ± 3.35*
Values are mean ± SD. of five individual observations Values in parentheses are per cent change over control - Denotes per cent decrease over control * Denotes that values are significant at P<0.05.
FIG. 1: BAR DIAGRAM SHOWING DECREASE IN PERCENT VIABILITY OF HepG-2 CELLS, WHEN TREATED WITH VARIOUS FRUIT EXTRACTS OF H. UNDATUS AT 24 H EXPOSURE
The inhibitory concentration (IC50) value was 112.43 µg/ml in aqueous extract, 99.13 µg/ml in chloroform extract, 102.68 µg/ml in ethyl acetate extract, 83.96 µg/ml in hexane extract and 69.09 µg/ml in methanol extract at 24 h incubation Table 3.
At the end of 24 h, methanol extract showed higher activity when compared with the other four extracts, which obviously shows that methanol fruit extract has a profound effect in controlling HepG-2 cell proliferation even at low concentration.
TABLE 3: IC50 VALUES OF HepG-2 CELLS WHEN TREATED WITH VARIOUS FRUIT EXTRACTS OF H.UNDATUS AT 24 H EXPOSURE
|S. no.||Sample||IC50 Value (µg/ml)|
Cytomorphological Changes: The morphological changes of HepG-2 cancer cells were photographed and presented in Fig. 2.
The control HepG-2 cancer cells showed irregular confluent aggregates with rounded and polygonal cell morphology.
On the other hand, treatment of the cells with H. undatus fruit pulp extracts at 24 h of incubation resulted in the shrinkage of polygonal cells, and it appeared spherical in shape.
The cell shrinkage increased progressively, and it was dose and time-dependent. The rate of shrinkage was high in methanol extract than that of other extracts.
FIG. 2: CELL MORPHOLOGY OF HepG-2 CELLS WHEN TREATED WITH IC50 CONCENTRATIONS OF VARIOUS FRUIT EXTRACTS OF H. UNDATUS AT 24 H EXPOSURE
DAPI Staining: To confirm whether the cytotoxic effect induced by methanol fruit extract of H. undatus involves apoptotic changes, the nuclear condensation was studied by the DAPI staining method. In the case of control cells, a very negligible number of positive cells were present. In case of cells treated with 69.09 µg/ml (IC50 24 h concentration) and 100 µg/ml (maximum concentration of methanol extract), a progressive increase in the number of the positive cell was observed Fig. 3. Methanol extract of H. undatus showed intense fragments of the nucleus as signs of apoptosis by DAPI staining.
FIG. 3: FLUORESCENCE MICROSCOPIC IMAGES OF HepG-2 CELLS, WHEN TREATED WITH 24 H IC50 CONCENTRATION AND MAXIMUM CONCENTRATION OF METHANOL EXTRACT OF H. UNDATUS
GC-MS Spectral Analysis: The results pertaining to GC-MS analysis led to the identification of a number of compounds from the GC fractions of methanol extract of H. undatus. The presence of functional groups as detected by our GC-MS study of H. undatus methanol fruit extract revealed that it contains 43 active compounds with different retention time and mass peak such as n-Hexa-decanoic acid, sEthyl 13-methyl- tetra-deconaa, 3, 7, 11, 15 - Tetramethyl - 2 - hexa, Z-10-Methyl-11-tetradecen-1, n-Propyl 11-octa-decenate, Oleic acid, n-propyl 9,12-octadecadienoa, Ethyl 9,12,15-octadecatrieno, Methyl 19-methyl-eicosanate, Stigmasterol, Tricosanoic acid, methylest, Vitamin E, Pebtacosanoic acid, methyl, 17-Pentatriacotene, Squalene, N-(2-(Hydrohy (oxide) amino)-4, 4,7-Benzofurandione, -3-acetyl, Octacosyl triflora-oroacetate, Pregn-4-ene-3,11,20-trione, 4H, 8H - Benzo [1, 2 - b: 3, 4 - b] dip, Anthraerzo-statetraenol, 1,11-Dicartoethocy-1-beta, Silane, dimethyl (dimethyloct), 9,19-cydo-chloestene-, Ɔ-dio, Gamne-tocophenol, 4, 7-Benzo-flurandione, 3,H-cyloprop (1,2)-5. Alpha, Rhodoxanthin, Miibe-mycin b, 1-chloro-5-de, 2, 4, 6-Decatrienoic acid ‘la’, Hceadecananids. N, N-dis £ [2, Mitheamycin B, 5-demethoxy-5, d1-alpha-Tocophenol, 17-(1,5-dimethyl)-10,13, 1,1′-Dicarbo-ethyoxy-1. Beta, 4, 7-Benzofurandion, 1, 11-Benzofurandion, Campes-terol, 4, 25-Secoobscurinerran-4-one and 9, 19-Cycloeryost-24(28)-en-3 Fig. 4.
FIG. 4: GC-MS CHROMATOGRAM OF H. UNDATUS METHANOL EXTRACT
DISCUSSION: Fruits are an important source of natural phytocomponents with wide spectrum of applications. The ‘greener’ environmentally friendly processes in chemistry, and chemical technology is becoming increasingly popular and are much needed as a result of worldwide problems associated with environmental contamination. In Indian traditional medicine, H. undatus is used for diabetes treatment and prevention, to treat acne, to lower cholesterol levels, to improve cardiovascular health and to boost immunity. The use of this fruit is enormous and people of various countries are using this fruit for renal, bone disease and another ayurvedic purpose. The development of new phyto-compounds with a high impact on cancer therapy is a major challenge in medicine. Hence, the present investigation demonstrates that phytochemistry can conquer the limitation of conventional therapies used in practice.
In our study the analysis of phytoconstituents of H. undatus showed the presence of carbohydrate, tannins, saponins, anthocyanin, quinones, cardiac glycosides, terpenoids, triterpenoids, phenols, acids and steroids in aqueous extract, carbohydrate, saponins, alkaloids, cardiac glycosides, triter-penoids, phenols and coumarins in chloroform extract, carbohydrate, tannins, saponins, flavo-noids, alkaloids, anthocyanin, cardiac glycosides, terpenoids, triterpenoids, acids, steroids in ethyl acetate, carbohydrate, saponins, anthocyanin, quinones, phenols and acids in hexane extract, carbohydrate, tannins, saponins, flavonoids, alkaloids, anthocyanin, cardiac glycosides, terpenoids, triterpenoids, phenols, acids and steroids in methanol extract. Similar phytochemical analysis was done in Emblica officinalis 23, Lycopersicon esculentum 24, Avicennia officinalis and Pleurotus pulmonarius 25, Momordica charantia 26, and Garcinia mangostana 7. It has been reported that H. undatus consists of 150.46 ± 2.19 mg of polyphenolic component such as betalains, galic acid, and betacyanins per 100 g of dry weight 27. In cacti, red-violet betacyanins and yellow betaxanthins are the most important fruit pigments, belonging to betalain pigment 28. Betalain is a class of water-soluble pigments that provide color in a wide range of flowers and fruits 29. Moreover, betacyanins that are attached to N-heterocyclic compounds are a class of compounds that can also be employed as antioxidants, with radical scavenging activities 30.
In our study, the IC50 value was 112.43 µǥ/ml in aqueous extract, 99.13 µǥ/ml in chloroform extract, 102.68 µǥ/ml in ethyl acetate extract, 83.96 µǥ/ml in hexane extract, and 69.09 µǥ/ml in methanol extract at 24 h incubation. Similar results were also reported by several authors 7, 8, 10, 11, 31, 32. Methanol extracts of the peels of dragon fruit showed anti-proliferative activity against AGS human gastric and MCF-7 breast cancer cells stronger than exhibited by the flesh extracts 33.
A positive correlation was found between peel and flesh content of polyphenols and flavonoids and their respective anti-proliferative activities. Negative correlations were found between the per cent cell viability of HeLa, AGS, and MCF-7 and the total polyphenol content 33. Chiku and “dragon fruit” extracts exhibited remarkable inhibition of cell proliferation. The results were attributed to the scavenging of the cell proliferation-inducing nitric oxide by phytochemicals included in the fruit extract, resulting in the inhibition of MCF-7 cell proliferation 34. The anticancer properties of Hylocereus species were recently studied by several authors 33-35. Several evidences showed that polyphenols, flavonoids, and betanins that present in the Hylocereus species are responsible for the anticancer effects 33-35. It has been observed that H. undatus peel extracted by ethanol-water (50:50,v/v) solvent system showed anti-proliferative activity towards human hepatocellular carcinoma cell line (HepG-2) in a dose-dependent manner, and it recorded an IC50 at 21.81 ± 0.01 mg/ml after 48 h of incubation 35.
The anticancer activity of our study also corroborates with the results of the above authors, thus finding support from their work. Polyphenols were believed to be the main phytochemical compound for such anti-cancer effect, although the exact compound is yet to be identified. The polyphenols act through scavenging nitric oxide (NO) free radicals that promote tumor vascularization and metastasis. Compounds that inhibited NO might be considered as potential anticancer agents. On the other hand, the presence of C2-C3 double bond and three adjacent hydroxyl groups in the flavonoids was also suggested to be crucial for anticancer effects 36-39. Betacyanins that have a similar molecular structure as flavonoids were proposed to have similar anti-cancer effects 33.
The nuclear changes caused by methanol fruit extract of H. Undatus, involving apoptotic changes and the nuclear condensation was studied by the DAPI staining method. A very negligible number of positive cells were present in control cells, while in methanol extract treated cells both at IC50 24 h concentration and maximum concentration, a progressive increase in the number of the positive cell was observed. Methanol extract of H. undatus showed intense fragments of the nucleus as signs of apoptosis by DAPI staining. Work on DAPI staining was conducted in Curcuma longa on leukemic cell lines 37, thus supporting the present work. The GC-MS spectra are a useful tool in identifying the presence of certain functional groups in a molecule, and to confirm the types of functional groups on the biosorbent before and after chemical modification. The presence of glycosides, terpenoids, triterpenoids, phenols, and acids in GC-MS suggests that H. undatus methanol fruit extract is pharmacologically active, supporting the claim by traditional healers. This result obtained is comparable to the reported phytochemical components, which indicate the presence of polysaccharides, flavonoids, phenol, betacyanins in H. polyrhizus, H. megalanthus, and H. undatus 40-42. It has been stated that phenolic acids constitute about one-third of the dietary phenols and they are present in free and bound forms 43. Bound-phenolic may link to various plant components through ester, ether or acetal bonds 44. The high content of polyphenols gives fruits remarkable antioxidant activity and may help lessen the risk of cancer 45. The presence of phenols, betalains, and other antioxidant agents in dragon fruit might also be the reason for exerting antioxidant properties leading to the anti-proliferation of HepG-2 cells treated with methanol extract of dragon fruit. In-toto, our study investigated the anti-cancer activity of H. undatus fruit extract as a whole. The preliminary screening studies on phytochemical constituents of H. undatus fruit extract confirmed that the phytoconstituents present in these extracts possess the best anticancer and apoptotic activity. The present study indicates the anti-cancer potential of H. undatus fruit pulp methanol extract, and further experiments await the characterization of the active principle responsible for anti-cancer property. This study may be the subject of experimental validation and clinical trials to establish these said analogous as more potent drugs to treat various cancers in the future.
CONCLUSION: In conclusion, the methanol fruit pulp extracts of H. undatus have demonstrated promising anticancer and anti-apoptotic properties against human liver cancer (HepG-2) cells by an in-vitro method. Increasing awareness, promotion, and utilization of this fruit for public benefits are highly encouraged, and the identification of active phytoconstituents in the fruit pulp will serve as a natural cytotoxic agent against various cancers.
ACKNOWLEDGEMENT: The authors thank Prof. P. Jayaraman, Institute of Herbal Botany, Plant Anatomy Research Centre, West Tambaram, Chennai, Tamil Nadu, India, for authentic identification of dragon fruit, V CLIN BIO LAB Pvt. Ltd, Sri Ramachandra Medical University, Porur, Chennai for cell line studies and NIOT Chennai for GC-MS analysis.
CONFLICTS OF INTEREST: The authors declare that there is no conflict of interest in this manuscript.
- Peedell C: Concise Clinical Oncology. Elsevier Butter-worth Heinemann Philadelphia USA 2005; 3-5.
- Jayaprakash P, Sivakumari K, Ashok K, Rajesh S, Prabhu D and Chandrasekar D: Anticancer potential of green synthesized silver nanoparticles of Sargassum wightii against human prostate cancer (PC-3) cell line. European Journal of Pharmaceutical and Medical Research 2017; 4(3): 275-87.
- Tavakoli J, Miar S, Zadehzare MM and Akbari H: Evaluation of effectiveness of herbal medication in cancer care: a review study. Iranian Journal of Cancer Prevention 2012; 5(3): 144-56.
- Mathew S, Faheem M, Archunan G, Ilyas M, Begum N, Jahangir S, Qadri I, Qahtani Mal and Mathew S: In-silico studies of medicinal compounds against hepatitis C capsid protein from North India. Bioinformatics and Biology Insights 2014; 8(8): 159-68.
- Marquardt JU, Andersen JB and Thorgeirsson SS: Functional and genetic deconstruction of the cellular origin in liver cancer. Nature Reviews Cancer 2015; 15(11): 653-67.
- Pawlotsky JM, Feld JJ, Zeuzem S and Hoofnagle JH: From non-A, non-B hepatitis to hepatitis C virus cure. Journal of Hepatology 2015; 62(1): 87-99.
- Manimekalai I, Sivakumari K, Ashok K and Rajesh S: Antioxidant and anticancer potential of mangosteen fruit, Garcinia mangostana against hepatocellular carcinoma (HepG-2) cell line. World Journal of Pharmacy and Pharmaceutical Sciences 2016; 5(2): 253-93.
- Manimekalai I, Sivakumari K, Ashok K and Rajesh S: Phytochemical profiling of mangosteen fruit, Garcinia mangostana. World Journal of Pharmacy and Pharma-ceutical Sciences 2016; 5(2): 221-52.
- Rajesh S, Sivakumari K and Ashok K: In-silico docking of selected compound from Cardiospermum halicacabum Leaf against human hepatocellular carcinoma (HepG-2) cell line. International Journal of Computational Bioinformatics and In-silico Modelli 2016; 5(2): 780-86.
- Rajesh S, Sivakumari K, Ashok K and Abitha AR: Anticancer activity of Cardiospermum halicacabum Leaf extracts against hepatocellular carcinoma cell line (HepG-2). World Journal of Pharmacy and Pharmaceutical Sciences 2016; 5(3): 1133-54.
- Hemalatha G, Sivakumari K, Rajesh S and Shyamala Devi K: Phytochemical profiling, anticancer and apoptotic activity of graviola (Annona muricata) fruit extract against human hepatocellular carcinoma (HepG-2) cells. International Journal of Zoology and Applied Biosciences 2020; 5(1): 32-47.
- Chatterjee R and Mitra A: An overview of effective therapies and recent advances in biomarkers for chronic liver diseases and associated liver cancer. International Immunopharmacology 2015; 24(2): 335-45.
- Smith-Hall C, Larsen HO and Pouliot M: People, plants and health: a conceptual framework for assessing changes in medicinal plant consumption. Journal of Ethnobiology and Ethnomedicine 2012; 8(1): 43-48.
- Weiss RF: Herbal Medicine: The Handbook of Herbal Medicine. (Ed.), Meuss AR, Translator. Edition 6 Beaconsfield Publishers Ltd UK 1998;
- Esquivel P, Stintzing FC and Carle R: Phenolic compound profiles and their corresponding antioxidant capacity of purple pitaya (Hylocereus sp.) genotypes. Zeitschrift fur Naturforschung C. Journal of Biosciences 2007; 62(9-10): 636-44.
- Nurliyana R, Syed Zahir I, Mustapha Suleiman K, Aisyah MR and Rahim K: Antioxidant study of pulps and peels of dragon fruits: a comparative study. International Food Research Journal 2010; 17(02): 512-18.
- Wybraniec S and Mizrahi Y: Fruit flesh betacyanin pigments in Hylocereus cacti. Journal of Agricultural and Food Chemistry 2002; 50(21): 6086-89.
- Abd Hadi N, Mohamad M, Rohin MAK and Yusof RM: Effects of red pitaya fruit (Hylocereus polyrhizus) consumption on blood glucose level and lipid profile in type 2 diabetic subjects. Borneo Science Journal 2012; 31(2): 113-29.
- Song H, Zheng Z, Wu J, Lai J, Chu Q and Zheng X: White pitaya (Hylocereus undatus) juice attenuates insulin resistance and hepatic steatosis in diet-induced obese mice. PloS One 2016; 11(2): 312-28.
- Kokate CK: Tannins: The Handbook of Pharmacognosy. Ed Edition 24 Nirali Prakashan Pune India 1988; 184.
- Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J of Immunological Methods 1983; 65(1-2): 55-63.
- Jang MH, Shin MC, Kang IS, Baik HH, Cho YH, Chu JP, Kim EH and Kim CJ: Caffeine induces apoptosis in human neuroblastoma cell line SK-N-MC. Journal of Korean Medical Science 2002; 17(5): 674-78.
- Chen KH, Lin BR, Chen CT and Ho CH: Emblica officinalis attentuates N-Nitrosodiethylamine-induced apoptosis, autophagy, and inflammation in rat livers. Journal of Medicinal Food 2011; 14(7-8): 746-55.
- Gupta P, Bansal MP and Koul A: Lycopene modulates initiation of N-nitrosodiethylamine induced hepato-carcinogenesis: Studies on chromosomal abnormalities, membrane fluidity and antioxidant defense system. Chemico Biological Interactions 2013; 206(2): 364-74.
- Xu WW, Li B, Lai ET, Chen L, Huang JJ, Cheung AL and Cheung PC: Water extract from Pleurotus pulmonarius with antioxidant activity exerts in-vivo chemoprophylaxis and chemosensitization for liver cancer. Nutrition and Cancer 2014; 66(6): 989-98.
- Zhang CZ, Fang EF, Zhang H-T, Liu LL and Yun JP: Momordica charantia lectin exhibits antitumor activity towards hepatocellular carcinoma. Investigational New Drugs 2014; 33(1): 1-11.
- Jamilah B, Shu CE, Kharidah M, Dzulkifly MA and Noranizan A: Physico-chemical characteristics of red pitaya (Hylocereus polyrhizus) peel. International Food Research Journal 2011; 18(01): 279-86.
- Stintzing FC, Schieber A and Carle R: Betacyanins in fruits from red-purple pitaya, Hylocereus polyrhizus (Weber) Britton & Rose. Food Chemistry 2002; 77(1): 101-06.
- Strack D, Vogt T and Schliemann W.: Recent advances in betalain research. Phytochemistry 2003; 62(3): 247-269.
- Wong YW and Siow LF: Effects of heat, pH, antioxidant, agitation and light on betacyanin stability using red-fleshed dragon fruit (Hylocereus polyrhizus) juice and concentrate as models. Journal of Food Science and Technology 2015; 52(5): 3086-92.
- Soerjomataram I, Oomen D, Lemmens V, Oenema A, Benetou V, Trichopoulou A, Coebergh JW, Barendregt J and de Vries E.: Increased consumption of fruit and vegetables and future cancer incidence in selected European countries. European Journal of Cancer 2010; 46(14): 2563-2580.
- Susanti VHE, Utomo SB, Syukri Y and Redjeki T: Phytochemical screening and analysis polyphenolic antioxidant activity of methanolic extract of white dragon fruit (Hylocereus undatus). Indonesian Journal of Pharmacy 2012; 23(1): 60-64.
- Wu LC, Hsu HW, Chen YC, Chiu CC, Lin YI and Ho JA: Antioxidant and anti-proliferative activities of red pitayas. Food Chemistry 2006; 95(2): 319-27.
- Jayakumar R and Kanthimathi MS: Inhibitory effects of fruit extracts on nitric oxide induced proliferation in MCF-7 cells. Food Chemistry 2011; 126(3): 956-60.
- Li F, Li S, Li H, Deng G, Ling W, Wu S, Xu X and Chen F: Anti-proliferative activity of peels, pulps and seeds of 61 fruits. Journal of Functional Foods 2013; 5(3): 1298-09.
- Jeong JH, Jung H, Lee SR, Lee HJ, Hwang KT and Kim TY: Anti-oxidant, anti-proliferative and anti-inflammatory activities of the extracts from black raspberry fruits and wine. Food Chemistry 2010; 123(2): 338-44.
- Hashim FJ, Shawkat MS and Aljewari H: Anti-cancer effect of Curcuma longa on leukemic cell lines evaluated by apoptosis and comet assay. International J of Pharmacy and Pharmaceutical Sciences 2013; 5(3): 671-74.
- Tenore GC, Novellino E and Basile A: Nutraceutical potential & antioxidant benefits of red pitaya (Hylocereus polyrhizus) extracts. Journal of Functional Foods 2012; 4(1): 129-36.
- Jayameena P, Sivakumari K, Ashok K and Rajesh S: In-vitro anti-inflammatory (membrane stabilization) and antioxidant potential of rutin. Research Journal of Life Sciences Bioinforamtics Pharmaceutical and Chemical Sciences 2018; 4(3): 265-74.
- Jayameena P, Sivakumari K, Ashok K and Rajesh S: Rutin: A potential anticancer drug against human colon cancer (HCT-116) cells. International Journal of Biology Pharmacy and Allied Sciences 2018; 7(9): 1731-45.
- Khalili RMA, Abdullah ABC and Manaf AA: Isolation and characterization of oligosaccharides composition in organically grown red pitaya, white pitaya and papaya. International Journal of Pharmacy and Pharmaceutical Sciences 2014; 6(2): 131-36.
- Chia SL and Chong GH: Effect of drum drying on physico-chemical characteristics of dragon fruit peel (Hylocereus polyrhizus). International Journal of Food Engineering 2015; 11(2): 285-93.
- Robbins RJ: Phenolic acids in foods: an overview of analytical methodology. Journal of Agricultural and Food Chemistry 2003; 51(10): 2866-87.
- Chalas J, Claise C, Edeas M, Messaoudi C, Vergnes L, Abella A and Linderbaum A: Effect of ethyl esterification of phenolic acids on low-density lipoprotein oxidation. Biomedicine & Pharmacotherapy 2001; 55(1): 54-60.
- Fu L, Xu BT, Xu XR, Gan RY, Zhang Y, Xia EQ and Li HB: Antioxidant capacities and total phenolic contents of 62 fruits. Food Chemistry 2011; 129(2): 345-50.
How to cite this article:
Padmavathy K, Sivakumari K, Karthika S, Rajesh S and Ashok K: Phytochemical profiling and anticancer activity of dragon fruit Hylocereus undatus extracts against human hepatocellular carcinoma cancer (hepg-2) cells. Int J Pharm Sci & Res 2021; 12(5): 2770-78. doi: 10.13040/IJPSR.0975-8232.12(5).2770-78.
All © 2013 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
K. Padmavathy, K. Sivakumari *, S. Karthika, S. Rajesh and K. Ashok
Department of Zoology, Presidency College, Chennai, Tamil Nadu, India.
12 May 2020
04 September 2020
15 September 2020
01 May 2021