CORRELATION OF ANTIOXIDANT AND ANTIPROLIFERATIVE ACTIVITY OF AMLA AND GINGER
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i8.26073Keywords:
Amla, Ginger aqueous extract, Cancer progression, Cancer stem cells, Antioxidant-induced cell deathAbstract
Objective: Our study focused on evaluating the anticancer property of ascorbic acid and aqueous extract of amla and ginger.
Methods: Antioxidant capacity of ascorbic acid, aqueous extract of amla, and ginger was obtained by 2,2-diphenyl-1-picrylhydrazyl method and total antioxidant capacity (TAC). Vero cell line, PA-1, Cal-27, Cal-27 CisR, and DysMSCTR16 cell lines were treated with antioxidants to evaluate its antiproliferative property using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Colony and spheroid formation assays were also carried out in the presence of extracts to assess its role in anticancer stem cell activity.
Results: Two volumes of amla 5 μl (~0.016 g) and 25 μl (~0.08 g) and ginger 5 μl (~0.02 g) and 25 μl (~0.1 g) showed TAC activity equivalent to 0.25 mM and 2 mM ascorbic acid, respectively. Amla and ascorbic acid showed significant antiproliferative property in normal (Vero) p=0.05, cancer (PA-1, Cal-27) p=0.005, and resistant (Cal-27 CisR) p=0.05 cell lines and ginger extract in Vero and Cal-27 cell lines (p=0.05). In PA-1 and Cal-27 CisR cell line, ginger extract showed proliferative activity (p=0.005). Antioxidants showed no antiproliferative activity in DysMSCTR16 cells. Amla extract and ascorbic acid showed significant inhibitory effect on spheroid (p=0.005) and colony formation capacity (p=0.0005) among dysplastic, cancer, and resistant cell lines. Ginger showed inhibitory effect (p=0.05) only in colony formation capacity.
Conclusion: Overall, we found a strong correlation between antioxidant and antiproliferative activity of ascorbic acid, amla, and ginger. Amla and ascorbic acid proved to be effective in controlling cell proliferation and self-renewal properties of cancer cells. However, ginger was found to have selective and less antiproliferative effect in comparison to amla.
Downloads
References
Bhatt ID, Rawat S, Badhani A, Rawal RS. Nutraceutical potential of selected wild edible fruits of the indian himalayan region. Food Chem 2017;215:84-91.
Wang CC, Yuan JR, Wang CF, Yang N, Chen J, Liu D, et al. Anti-inflammatory effects of phyllanthus emblica l on benzopyrene-induced precancerous lung lesion by regulating the il-1beta/mir-101/lin28b signaling pathway. Integr Cancer Ther 2017;16:505-15.
De A, Powers B, De A, Zhou J, Sharma S, Van Veldhuizen P, et al. Emblica officinalis extract downregulates pro-angiogenic molecules via upregulation of cellular and exosomal mir-375 in human ovarian cancer cells. Oncotarget 2016;7:31484-500.
Susanti SK, Santoso IS, Murwanti R, Suzery M, Oku H.Comparison on the cancer specific cytotoxicity of three gingers (Zingiber officinale rosc) leaves varieties from indonesia. Int J Pharm Phytochem Res 2017;9:129-34.
Kalantari K, Moniri M, Boroumand Moghaddam A, Abdul Rahim R, Bin Ariff A, Izadiyan Z, et al. A review of the biomedical applications of zerumbone and the techniques for its extraction from ginger rhizomes. Molecules 2017;22:pii: E1645.
Marx W, Ried K, McCarthy AL, Vitetta L, Sali A, McKavanagh D, et al. Ginger-mechanism of action in chemotherapy-induced nausea and vomiting: A review. Crit Rev Food Sci Nutr 2017;57:141-6.
Pournaderi PS, Yaghmaei P, Khodaei H, Noormohammadi Z, Hejazi SH. The effects of 6-gingerol on reproductive improvement, liver functioning and cyclooxygenase-2 gene expression in estradiol valerate - induced polycystic ovary syndrome in wistar rats. Biochem Biophys Res Commun 2017;484:461-6.
Zheng J, Zhou Y, Li Y, Xu DP, Li S, Li HB, et al. Spices for prevention and treatment of cancers. Nutrients 2016;8:pii: E495.
Roomi MW, Kalinovsky T, Rath M, Niedzwiecki A. A specific mixture of nutrients suppresses ovarian cancer A-2780 tumor incidence, growth, and metastasis to lungs. Nutrients 2017;9: pii: E303.
Fredotovic Z, Sprung M, Soldo B, Ljubenkov I, Budic-Leto I, Bilusic T, et al. Chemical composition and biological activity of allium cepa l. And allium x cornutum (clementi ex visiani 1842) methanolic extracts. Molecules 2017;22:pii: E448.
Egnell M, Fassier P, Lecuyer L, Gonzalez R, Zelek L, Vasson MP, et al. Antioxidant intake from diet and supplements and risk of digestive cancers in middle-aged adults: Results from the prospective nutrinet-sante cohort. Br J Nutr 2017;118:541-49.
Wilms D, Andra J.Comparison of patient-derived high and low phosphatidylserine-exposing colorectal carcinoma cells in their interaction with anti-cancer peptides. J Pept Sci 2017;23:56-67.
Leong SY, Burritt DJ, Hocquel A, Penberthy A, Oey I. The relationship between the anthocyanin and vitamin c contents of red-fleshed sweet cherries and the ability of fruit digests to reduce hydrogen peroxide-induced oxidative stress in caco-2 cells. Food Chem 2017;227:404-12.
Ashita S, Mandeep K, Jatinder Kaur K, Avinash Kaur N. Polyphenols in food: Cancer prevention and apoptosis induction. Current Medicinal Chemistry 2017;24:1-18.
Shivakumar A, Yogendra Kumar MS. Critical review on the analytical mechanistic steps in the evaluation of antioxidant activity. Crit Rev Anal Chem 2018;48:214-36.
Suarez-Arroyo IJ, Loperena-Alvarez Y, Rosario-Acevedo R, Martinez- Montemayor MM. Ganoderma spp.: A promising adjuvant treatment for breast cancer. Medicines (Basel) 2017;4:1-29.
Li T, Fu X, Tse AK, Guo H, Lee KW, Liu B, et al. Inhibiting stat3 signaling is involved in the anti-melanoma effects of a herbal formula comprising sophorae flos and lonicerae japonicae flos. Sci Rep 2017;7:3097.
Roter DL, Yost KJ, O’Byrne T, Branda M, Leppin A, Kimball B, et al. Communication predictors and consequences of complementary and alternative medicine (cam) discussions in oncology visits. Patient Educ Couns 2016;99:1519-25.
Ohkoshi E, Umemura N. Induced overexpression of cd44 associated with resistance to apoptosis on DNA damage response in human head and neck squamous cell carcinoma cells. Int J Oncol 2017;50:387-95.
Naik PP, Das DN, Panda PK, Mukhopadhyay S, Sinha N, Praharaj PP, et al. Implications of cancer stem cells in developing therapeutic resistance in oral cancer. Oral Oncol 2016;62:122-35.
Simple M, Suresh A, Das D, Kuriakose MA. Cancer stem cells and field cancerization of oral squamous cell carcinoma. Oral Oncol 2015;51:643-51.
Kulsum S, Sudheendra HV, Pandian R, Ravindra DR, Siddappa G, R N, et al. Cancer stem cell mediated acquired chemoresistance in head and neck cancer can be abrogated by aldehyde dehydrogenase 1 A1 inhibition. Mol Carcinog 2017;56:694-711.
Siddappa G, Kulsum S, Ravindra DR, Kumar VV, Raju N, Raghavan N, et al. Curcumin and metformin-mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells. Mol Carcinog 2017;56:2446-60.
Prieto P, Pineda M, Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal Biochem 1999;269:337-41.
Mensor LL, Menezes FS, Leitão GG, Reis AS, dos Santos TC, Coube CS, et al. Screening of brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. Phytother Res 2001;15:127-30.
Abubakar IB, Lim KH, Kam TS, Loh HS. Enhancement of apoptotic activities on brain cancer cells via the combination of γ-tocotrienol and jerantinine A. Phytomedicine 2017;30:74-84.
Adaramoye O, Erguen B, Nitzsche B, Höpfner M, Jung K, Rabien A, et al. Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cells. Chem Biol Interact 2017;274:100-6.
Afrin S, Forbes-Hernandez TY, Gasparrini M, Bompadre S, Quiles JL, Sanna G, et al. Strawberry-tree honey induces growth inhibition of human colon cancer cells and increases ROS generation: A Comparison with manuka honey. Int J Mol Sci 2017;18:pii: E613.
Vitale M, Vaccaro O, Masulli M, Bonora E, Del Prato S, Giorda CB, et al. Polyphenol intake and cardiovascular risk factors in a population with Type 2 diabetes: The TOSCA.IT study. Clin Nutr 2017;36:1686 92.
Nunez-Sanchez MA, Gonzalez-Sarrias A, Garcia-Villalba R, Monedero-Saiz T, Garcia-Talavera NV, Gomez-Sanchez MB, et al. Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: A randomized clinical trial. J Nutr Biochem 2017;42:126-33.
Venkata KC, Anand S, Debasis B, Anupam B. A small plant with big benefits: Fenugreek (trigonella foenum-graecum linn.) for disease prevention and health promotion. Molecular Nutrition & Food Research 2017;61:1600950.
Colomer R, Sarrats A, Lupu R, Puig T. Natural polyphenols and their synthetic analogs as emerging anticancer agents. Curr Drug Targets 2017;18:147-59.
Tafazoli A. Coenzyme q10 in breast cancer care. Future Oncol 2017;13:1035-41.
Nikseresht M, Kamali AM, Rahimi HR, Delaviz H, Toori MA, Kashani IR, et al. The hydroalcoholic extract of matricaria chamomilla suppresses migration and invasion of human breast cancer mda-mb-468 and mcf-7 cell lines. Pharmacognosy Res 2017;9:87-95.
Ashraf K, Sultan S, Shah SA. Phychemistry, phytochemical, pharmacological and molecular study of zingiber officinale roscoe: A review. Int J Pharm Pharm Sci 2017;9:8-16.
Pounis G, Di Castelnuovo A, Bonaccio M, Costanzo S, Persichillo M, Krogh V, et al. Flavonoid and lignan intake in a mediterranean population: Proposal for a holistic approach in polyphenol dietary analysis, the moli-sani study. Eur J Clin Nutr 2016;70:338-45.
Bastide N, Dartois L, Dyevre V, Dossus L, Fagherazzi G, Serafini M, et al. Dietary antioxidant capacity and all-cause and cause-specific mortality in the e3n/epic cohort study. Eur J Nutr 2017;56:1233-43.
Bakker MF, Peeters PH, Klaasen VM, Bueno-de-Mesquita HB, Jansen EH, Ros MM, et al. Plasma carotenoids, vitamin c, tocopherols, and retinol and the risk of breast cancer in the european prospective investigation into cancer and nutrition cohort. Am J Clin Nutr 2016;103:454-64.
Noh H, Freisling H, Assi N, Zamora-Ros R, Achaintre D, Affret A, et al. Identification of urinary polyphenol metabolite patterns associated with polyphenol-rich food intake in adults from four European countries. Nutrients 2017;9:pii: E796.
Vece MM, Agnoli C, Grioni S, Sieri S, Pala V, Pellegrini N, et al. Dietary total antioxidant capacity and colorectal cancer in the italian epic cohort. PLoS One 2015;10:e0142995.
Jeurnink SM, Ros MM, Leenders M, van Duijnhoven FJ, Siersema PD, Jansen EH, et al. Plasma carotenoids, vitamin c, retinol and tocopherols levels and pancreatic cancer risk within the European prospective investigation into cancer and nutrition: A nested case-control study: Plasma micronutrients and pancreatic cancer risk. Int J Cancer 2015;136:E665-76.
Dai F, Liu GY, Li Y, Yan WJ, Wang Q, Yang J, et al. Insights into the importance for designing curcumin-inspired anticancer agents by a prooxidant strategy: The case of diarylpentanoids. Free Radic Biol Med 2015;85:127-37.
Lea MA. Flavonol regulation in tumor cells. J Cell Biochem 2015;116:1190-4.
Tao L, Park JY, Lambert JD. Differential prooxidative effects of the green tea polyphenol, (-)-epigallocatechin-3-gallate, in normal and oral cancer cells are related to differences in sirtuin 3 signaling. Mol Nutr Food Res 2015;59:203-11.
Lee WJ. The prospects of vitamin c in cancer therapy. Immune Netw 2009;9:147-52.
Ramaswamy JS, Reddy CU. Comparative study of in silico and in vitro anticancer activity of traditional indian medicinal plants-a reverse pharmacological approach. Int J Curr Pharm Res 2017;9:42-6.
Alamdari DH, Aghasizadeh-Sharbaf M, Mohadjerani M, Ferns GA, Avan A. Prooxidant-antioxidant balance and antioxidant properties of thuja orientalis l: A potential therapeutic approach for diabetes mellitus. Curr Mol Pharmacol 2018;11:109-12.
Andrade Volkart P, Benedetti Gassen R, Mühlen Nogueira B, Nery Porto B, Eduardo Vargas J, Arigony Souto A, et al. Antitumor activity of resveratrol is independent of cu(II) complex formation in MCF-7 cell line. Bioorg Med Chem Lett 2017;27:3238-42.
Fernandes AP, Gandin V. Selenium compounds as therapeutic agents in cancer. Biochim Biophys Acta 2015;1850:1642-60.
Hu K, Yin F, Yu M, Sun C, Li J, Liang Y, et al. In-tether chiral center induced helical peptide modulators target p53-mdm2/mdmx and inhibit tumor growth in stem-like cancer cell. Theranostics 2017;7:4566-76.
Eren D, Betul YM. Revealing the effect of 6-gingerol, 6-shogaol and curcumin on mpges-1, gsk-3beta and beta-catenin pathway in a549 cell line. Chem Biol Interact 2016;258:257-65.
Kaur IP, Deol PK, Kondepudi KK, Bishnoi M. Anticancer potential of ginger: Mechanistic and pharmaceutical aspects. Curr Pharm Des 2016;22:4160-72.
Kapoor V, Aggarwal S, Das SN. 6-gingerol mediates its anti tumor activities in human oral and cervical cancer cell lines through apoptosis and cell cycle arrest. Phytother Res 2016;30:588-95.
Chavare A, Chowdari P, Ghosh S, Pawar P, Patkar M, Dakave S, et al. Safety and bioactivity studies of jasad bhasma and its in-process intermediate in swiss mice. J Ethnopharmacol 2017;197:73-86.
Saraphanchotiwitthaya PS. Immunomodulatory effect of different proportions of the herbal mixture in triphala on human t lymphocytes (molt-4). Int J Pharm Pharm Sci 2015;7:282-8.
Gopalsamy B, Farouk AA, Mohamad TA, Sulaiman MR, Perimal EK. Antiallodynic and antihyperalgesic activities of zerumbone via the suppression of il-1beta, il-6, and tnf-alpha in a mouse model of neuropathic pain. J Pain Res 2017;10:2605-19.
Mekuria AB, Erku DA, Gebresillassie BM, Birru EM, Tizazu B, Ahmedin A. Prevalence and associated factors of herbal medicine use among pregnant women on antenatal care follow-up at university of gondar referral and teaching hospital, ethiopia: A cross-sectional study. BMC Complement Altern Med 2017;17:86.
Kulkarni RA, Deshpande AR. Anti-inflammatory and antioxidant effect of ginger in tuberculosis. J Complement Integr Med 2016;13:201-6.
Johri RK, Zutshi U. An ayurvedic formulation ‘trikatu’ and its constituents. J Ethnopharmacol 1992;37:85-91.
Ashraf SS, Shah SA. Phychemistry, phytochemical, pharmacological and molecular study of Zingiber officinale roscoe: A review. Int J Pharm Pharm Sci 2017;9:8-16.
Krishnamoorthy D, Sankaran M. Modulatory effect of pleurotus ostreatus on oxidant/antioxidant status in 7, 12-dimethylbenz (a) anthracene induced mammary carcinoma in experimental rats--a dose-response study. J Cancer Res Ther 2016;12:386-94.
Gunasekaran V, Elangovan K, Devaraj SN. Targeting hepatocellular carcinoma with piperine by radical-mediated mitochondrial pathway of apoptosis: An in vitro and in vivo study. Food Chem Toxicol 2017;105:106-18.
Choi EJ. Evaluation of equol function on anti-or prooxidant status in vivo. J Food Sci 2009;74:H65-71.
Stolzenberg-Solomon RZ, Sheffler-Collins S, Weinstein S, Garabrant DH, Mannisto S, Taylor P, et al. Vitamin e intake, alpha-tocopherol status, and pancreatic cancer in a cohort of male smokers. Am J Clin Nutr 2009;89:584-91.
Lin ZY, Chuang WL. Pharmacologic concentrations of ascorbic acid cause diverse influence on differential expressions of angiogenic chemokine genes in different hepatocellular carcinoma cell lines. Biomed Pharmacother 2010;64:348-51.
del Bello B, Paolicchi A, Comporti M, Pompella A, Maellaro E. Hydrogen peroxide produced during gamma-glutamyl transpeptidase activity is involved in prevention of apoptosis and maintainance of proliferation in u937 cells. FASEB J 1999;13:69-79.
Soo E, Thakur S, Qu Z, Jambhrunkar S, Parekh HS, Popat A. Enhancing delivery and cytotoxicity of resveratrol through a dual nanoencapsulation approach. J Colloid Interface Sci 2016;462:368-74.
Ganjam GK, Chi TF, Kietzmann T, Dimova EY. Resveratrol: Beneficial or not? Opposite effects of resveratrol on hypoxia-dependent pai-1 expression in tumour and primary cells. Thromb Haemost 2016;115:461-3.
Do QD, Angkawijaya AE, Tran-Nguyen PL, Huynh LH, Soetaredjo FE, Ismadji S, et al. Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of limnophila aromatica. J Food Drug Anal 2014;22:296-302.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
