In this study, the fruits of both mature and air-dried figs were exposed to selective sequential extracting processes using soxhlet. Different polarity and non-polarity solvents were used to increase the yield of the isolated extracts. Methanol, ethyl acetate, chloroform, and n-hexane were used to precipitate and isolate the effective compound 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na from 11 extracts and 7 compounds extracted from the organic layer. Various spectral techniques were applied, including UV-spectroscopy, FT-IR, GC-Mass, 1H-NMR, and 13C-NMR for the detection of the precipitate. The aim of current work is to deal with the synthesis of a novel compound 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na from fig fruit and study its effect as anticancer and anti-proliferative agent against SKOV-3, and AMJ-13 cells. The effect of the active compound on breast cancer cells, ovarian cancer cell proliferation was measured by the MTT assay, while its ability to induce apoptosis was detected using DAPI, acridine orange/ethidium bromide (AO/EtBr) staining, flow cytometry assay and finally mitochondrial membrane potential (MMP). Real-Time PCR was used to detect changes in the expression of mRNA for Bax and Bcl-2, P53, caspase-8, and caspase-9. Treated cancer cells with 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na significantly increased ROS synthesis, with subsequent reduction of the MMP through mechanisms that included Bax upregulation P53, Caspase-8, and Caspase-9 and Bcl-2 downregulation. The outcomes of the current study show that 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na extracted from fig fruit suppressed cancers cells’ proliferation, resulting in apoptosis as a novel pathway that involves mitochondrial mechanism via activated P53 and caspase-8 signaling. In addition, the extract exerted no toxic effects, neither on serum levels of liver functional enzymes nor on the normal histological architecture of the lungs and spleen. We demonstrated how the 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na affects cancer cells along with a study the possible mechanisms involved in this effect which is mitochondrial damage and P53 pathway. We conclude that 2-benzhydrylsulfinyl-n-hydroxyacetamide-Na holds a promising potential as an anticancer therapeutic agent.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Abdel-Aty AM, Hamed MB, Salama WH, Ali MM, Fahmy AS, Mohamed SA (2019) Ficus carica, Ficus sycomorus and Euphorbia tirucalli latex extracts: phytochemical screening, antioxidant and cytotoxic properties. Biocatal Agric Biotechnol 20:101199. https://doi.org/10.1016/j.bcab.2019.101199
Bamodu OA, Huang WC, Tzeng DT, Wu A, Wang LS, Yeh CT (2015) Ovatodiolide sensitizes aggressive breast cancer cells to doxorubicin anticancer activity, eliminates their cancer stem cell-like phenotype, and reduces doxorubicin-associated toxicity. Cancer Lett 364(2):125–134. https://doi.org/10.1016/j.canlet.2015.05.006
Rufa’I UZ, Hidayah AB, Swethadri GK, Atif B, Idris MA, Maryam IU (2015) Non-toxic antiproliferative effect of Ficus carica fruit extracts on estrogen receptor positive breast cancer cell (MCF-7). J Chem Pharm Res 7(10):815–821
Bhadoria AS, Kapil U, Sareen N, Singh P (2013) A case-control study in tertiary care hospitals of North India. Indian J Cancer 50(4):316–321. https://doi.org/10.4103/0019-509X.123606
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. https://doi.org/10.3322/caac.20107
Bharti AC, Takada Y, Aggarwal BB (2004) Curcumin (Diferuloylmethane) inhibits receptor activator of NF-κB ligand-induced NF-κB activation in osteoclast precursors and suppresses osteoclastogenesis. J Immunol 172(10):5940–5947. https://doi.org/10.4049/jimmunol.172.10.5940
Celik H, Aydin T, Solak K, Khalid S, Farooqi AA (2018) Curcumin on the “flying carpets” to modulate different signal transduction cascades in cancers: next-generation approach to bridge translational gaps. J Cell Biochem 119(6):4293–4303. https://doi.org/10.1002/jcb.26749
Farhan M, Malik A, Ullah FM, Afaq S, Faisal M, Farooqi AA, Biersack B, Schobert R, Ahmad A (2019) Garcinol Sensitizes NSCLC Cells to Standard Therapies by Regulating EMT-Modulating miRNAs. Int J Mol Sci 20 (4). doi: 10.3390/ijms20040800
Mann J (2002) Natural products in cancer chemotherapy: past, present and future. Nat Rev Cancer 2(2):143–148. https://doi.org/10.1038/nrc723
Batra P, Sharma AK (2013) Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech 3(6):439–459. https://doi.org/10.1007/s13205-013-0117-5
Shamkant BB, Vainav VP, Atmaram HB, Raghunath TM (2014) Traditional uses phytochemistry and pharmacology of Ficus carica. Pharm Biol 52(11):1487–1503. https://doi.org/10.3109/13880209.2014.892515
Solomon A, Golubowicz S, Yablowicz Z, Grossman S, Bergman M, Gottlieb HE, Altman A, Kerem Z, Flaishman MA (2006) Antioxidant activities and anthocyanin content of fresh fruits of common fig (Ficus carica L.). J Agric Food Chem 54(20):7717–7723. https://doi.org/10.1021/jf060497h
Barolo MI, Ruiz Mostacero N, López SN (2014) Ficus carica L. (Moraceae): an ancient source of food and health. Food Chem 164:119–127. https://doi.org/10.1016/j.foodchem.2014.04.112
Jing L, Zhang YM, Luo JG, Kong LY (2015) Tirucallane-type triterpenoids from the fruit of Ficus carica and their cytotoxic activity. Chem Pharm Bull 63(3):237–243. https://doi.org/10.1248/cpb.c14-00779
Tian J, Zhang Y, Yang X et al (2014) Ficus carica polysaccharides promote the maturation and function of dendritic cells. Int J Mol Sci 15(7):12469–12479. https://doi.org/10.3390/Ijms150712469
Yang J, He D, Peng Y et al (2017) Matrine suppresses the migration and invasion of NSCLC cells by inhibiting PAX2-induced epithelialmesenchymal transition. Onco Targets Ther 10:5209–5217. https://doi.org/10.2147/OTT.S149609
Ikegami H, Nogata H, Inoue Y et al (2013) Expression of FcFT1, a flowering locus T-like gene, is regulated by light and associated with inflorescence differentiation in fig (Ficus carica L.). BMC Plant Biol 13:216. https://doi.org/10.1186/1471-2229-13-216
Zhang Yu, Wan Y, Huo Bo, Li B, Jin Y, Xin Hu (2018) Extracts and components of Ficus carica leaves suppress survival, cell cycle, and migration of triple-negative breast cancer MDA-MB-231 cells. OncoTargets Ther 11:4377–4386. https://doi.org/10.2147/OTT.S171601
Kim SS, Cho H-J, Cho J-M, Kang JY, Yang H-W, Yoo TK (2013) Dual silencing of Hsp27 and c-FLIP enhances doxazosin-induced apoptosis in PC-3 prostate cancer cells. Sci World J 2013:7. https://doi.org/10.1155/2013/174392
Ocker M, Höpfner M (2012) Apoptosis-modulating drugs for improved cancer therapy. Eur Surg Res 48(3):111–120. https://doi.org/10.1159/000336875
Schumacker PT (2006) Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell 10(3):175–176. https://doi.org/10.1016/j.ccr.2006.08.015
Simon HU, Haj-Yehia A, Levi-Schaffer F (2000) Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 5(5):415–418. https://doi.org/10.1023/A:1009616228304
Martinou J-C, Youle RJ (2011) Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell 21(1):92–101. https://doi.org/10.1016/j.devcel.2011.06.017
Yao K, Gietema JA, Shida S, Selvakumaran M, Fonrose X, Haas NB, Testa J, O'Dwyer PJ (2005) In vitro hypoxia-conditioned colon cancer cell lines derived from HCT116 and HT29 exhibit altered apoptosis susceptibility and a more angiogenic profile in vivo. Br J Cancer 93(12):1356–1363. https://doi.org/10.1038/sj.bjc.6602864
Ivanov I, Dincheva I, Badjakov I, Petkova N, Denev P, Pavlov A (2018) GC-MS analysis of unpolar fraction from Ficus carica L. (fig) leaves. Int Food Res J 25(1):282–286
Ivanov I, Dencheva N, Petkova N, Denev P (2015) Determination of total polyphenols and antioxidant activity of different extracts from Ficus carica L. leaves. Appl Res Tech Technol Educ 3:87–92
Quisenberry AJ, Baker LE (2015) Dopaminergic mediation of the discriminative stimulus functions of modafinil in rats. Psychopharmacology 232(24):4411–4419. https://doi.org/10.1007/s00213-015-4065-0
Jie JL, Douglas SJ (2010) Modern drug synthesis. Wiley, New York, pp 2. ISBN 978-1-118-70124-9. Doi: 10.1002/9780470768594
Al-Hashimia AG, Al-Salman HN, Al-Jadaan NA (2018) GC-mass analysis and estimation of pomegranate husks extracts and the biological efficacy of compound tri-butyl acetyl citrate as one of the extract against food fungi. Orient J Chem 34(4):2089–2097. https://doi.org/10.13005/ojc/3404049
Albukhaty S, Naderi-Manesh H, Tiraihi T, Sakhi Jabir M (2018) Poly-l-lysine-coated superparamagnetic nanoparticles: a novel method for the transfection of pro-BDNF into neural stem cells. Artif Cells Nanomed Biotechnol 46(3):S125–S132. https://doi.org/10.1080/21691401.2018.1489272
Ali SH, Sulaiman GM, Al-Halbosiy MMF, Jabir MS, Hameed AH (2019) Fabrication of hesperidin nanoparticles loaded by poly lactic co-Glycolic acid for improved therapeutic efficiency and cytotoxicity. Artif Nanomed Biotechnol 47(1):378–394. https://doi.org/10.1080/21691401.2018.1559175
Ali Z, Jabir M, Al-Shammari A (2019) Gold nanoparticles inhibiting proliferation of human breast cancer cell line. Res J Biotechnol 14:79–82
Khashan KS, Jabir MS, Abdulameer FA (2018) Carbon nanoparticles decorated with cupric oxide nanoparticles prepared by laser ablation in liquid as an antibacterial therapeutic agent. Mater Res Express. https://doi.org/10.1088/2053-1591/aab0ed
Alsaedi IIJ, Taqi ZJ, Abdul Hussien AM, Sulaiman GM, Jabir MS (2019) Graphene nanoparticles induces apoptosis in MCF-7 cells through mitochondrial damage and NF-KB pathway. Mater Res Express 6(9):095413. https://doi.org/10.1088/2053-1591/ab33af
Kadhem H, Ibraheem S, Jabir M, Kadhim A, Taqi Z, Florin M (2019) Zinc Oxide nanoparticles induces apoptosis in human breast cancer cells via caspase-8 and P53 pathway. Nano Biomed Eng 11(1):35–43. https://doi.org/10.5101/nbe.v11i1.p35-43
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262
Ali IH, Jabir MS, Al-Shmgani HSA, Sulaiman GM, Sadoon AH (2018) Pathological and immunological study on infection with Escherichia Coli in ale BALB/c mice. J Phys Conf Ser 1003:012009. https://doi.org/10.1088/1742-6596/1003/1/012009
Jabir MS, Taha AA, Sahib UI (2018) Linalool loaded on glutathione-modified gold nanoparticles: a drug delivery system for a successful antimicrobial therapy. Artif Cells Nanomed Biotechnol 46(2):345–355. https://doi.org/10.1080/21691401.2018.1457535
Khodarahmi GA, Ghasemi N, Hassanzadeh F, Safaie M (2011) Cytotoxic effects of different extracts and latex of Ficus carica L. on HeLa cell line. Iran J Pharm Res 10(2):273–277
Mustapha N, Pinon A, Limami Y, Simon A, Ghedira K, Hennebelle T, Chekir-Ghedira L (2016) Crataegus azarolus leaves induce antiproliferative activity, cell cycle arrest, and apoptosis in human HT-29 and HCT-116 colorectal cancer cells. J Cell Biochem 117(5):1262–1272. https://doi.org/10.1002/jcb.25416
Rubnov S, Kashman Y, Rabinowitz R, Schlesinger M, Mechoulam R (2001) Suppressors of cancer cell proliferation from Fig (Ficus carica) resin: isolation and structure elucidation. J Nat Prod 64(7):993–996. https://doi.org/10.1021/np000592z
Ullman S, Clark G, Roan K (1952) The effects of the fraction R3 of the latex of Ficus carica L. on the tissues of mice bearing spontaneous mammary tumors. Exp Med Surg 10(4):287–305
Jabir MS, Taha AA, Sahib UI, Taqi ZJ, Al-Shammari AM, Salman AS (2019) Novel of nano delivery system for Linalool loaded on gold nanoparticles conjugated with CALNN peptide for application in drug uptake and induction of cell death on breast cancer cell line. Mater Sci Eng C 94:949–964. https://doi.org/10.1016/j.msec.2018.10.014
The authors are warmly grateful to all those working in analytical research laboratories who have made a lot of effort to achieve the results of this research. The authors report that this work was supported by the laboratories of the Department of Chemistry, University of Sheffield, UK. College of the Pharmacy, University of Basrah, Basrah, Iraq and Department of Applied Sciences, University of Technology, Baghdad, Iraq.
Conflict of interest
We authors declare that we do not have any conflict of interest.
Compliance with ethics requirements
All Institutional and National Guidelines for the care and use of animals were followed and approved by Animal Care and Ethics Committee at Biotechnology Division, Applied Sciences Department, University of Technology, Baghdad, Iraq according to Ref. No. AS 569/12/01/2019.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Al-Salman, H.N.K., Ali, E.T., Jabir, M. et al. 2-Benzhydrylsulfinyl-N-hydroxyacetamide-Na extracted from fig as a novel cytotoxic and apoptosis inducer in SKOV-3 and AMJ-13 cell lines via P53 and caspase-8 pathway. Eur Food Res Technol 246, 1591–1608 (2020). https://doi.org/10.1007/s00217-020-03515-x
- Anticancer activity