Antioxidant properties and anticancer activity of Olea europaea L. olive and Ficus carica fruit extracts against pancreatic cancer cell lines

Subject Areas : Medicinal and Herbal Plants

Nadia Dekdouk ¹ , Souad Ameddah ² , Chawki Bensouici ³ , Meghboun Ibtissem ⁴ , Menad Ahmed ⁵ , Fatima Martel ⁶

1 - Laboratoire de Biologie et Environnement, Faculté des Sciences de la Nature et de la Vie, Université des Frères Mentouri Constantine1, Algérie
2 - Laboratoire de Biologie et Environnement, Faculté des Sciences de la Nature et de la Vie, Université des Frères Mentouri Constantine1, Algérie
3 - Biotechnology Research Center (CRBt), Ali Mendjli, Constantine, Algérie
4 - Biotechnology Research Center (CRBt), Ali Mendjli, Constantine, Algérie
5 - Laboratoire de Biologie et Environnement, Faculté des Sciences de la Nature et de la Vie, Université des Frères Mentouri Constantine1, Algérie
6 - Unit of Biochemistry, Dept. of Biomedicine Faculty of Medicine of Porto 4200-319 Porto portugal

Received: 2023-11-16 Accepted : 2024-06-12 Published : 2024-09-21

Keywords: Antioxidant capacity, Anti-pancreatic cancer effect, Antiproliferative, Cytotoxic, Fig extract, Olive extract, Phytochemical composition,

Abstract :

Olea europaea (OFE) and Ficus carica (FFE) extracts have shown anticancer activity. In the currents report, we aim to evaluate the phytochemical composition, antioxidant properties and anticancer activity of OFE and FFE against PANC-1 and AsPC-1 pancreatic cancer cell lines. OFE possessed higher phenolic, flavonoid content and antioxidant ability than FFE. OFE and FFE induced a cytotoxic effect and their combination resulted in an increased cytotoxicity. OFE showed an antiproliferative effect while FFE had no effect. Combination of the two extracts resulted in an antiproliferative effect similar to that of OFE. OFE showed an antimigratory effect, while FFE exhibited a promigratory effect. Interestingly, combination of the two extracts resulted in an anti-migratory effect similar to that caused by OFE. In view of the findings of this study, these extracts could be considered potential sources of natural compounds with antioxidant and anti-pancreatic cancer effects. The combination of these extracts should be further investigated in the context of pancreatic cancer.

References:

Akl, M.R., Ayoub, N.M., Mohyeldin, M.M., Busnena, B.A., Foudah, A.I., Liu, Y.Y., Sayed, K.A.E., 2014. Olive phenolics as c-Met inhibitors:(-)-Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models. PLoS One 9, e97622.
Al Salman, H.N.K., Ali, E.T., Jabir, M., Sulaiman, G.M., Al Jadaan, S.A.S., 2020. 2 Benzhydrylsulfnyl N hydroxyacetamide Na extracted from fig as a novel cytotoxic and apoptosis inducer in SKOV 3 and AMJ 13 cell lines viaP53 and caspase 8 pathway. Eur. Food Res. Technol. 246, 1591-1608.
Apak, R., Güçlü, K., Özyürek, M., Çelik, S.E., 2008. Mechanism of antioxidant capacity assays and the CUPRAC (cupric ion reducing antioxidant capacity) assay. Microchim. Acta 160, 413-419.
Arvaniti, O.S., Samaras, Y., Gatidou, G., Thomaidis,N.S., Stasinakis, A.S., 2019. Review on fresh and dried figs: Chemical analysis and occurrence of phytochemical compounds, antioxidant capacity and health effects. Food Res. Int. 119, 244-267.
Baby, J., Justin, S.R., 2011. Pharmacognostic and phytochemical properties of Ficus carica. Linn. Int. J. Pharm. Tech. Res. 3, 8-12.
Bachir Bey, M., Louaileche, H., 2015. A comparative study of phytochemical profile and in vitro antioxidant activities of dark and light dried fig (Ficus carica L.) varieties. J. Phytopharmacol. 4, 41-48.
Baldo, B.A., Pham, N.H., 2013. Adverse reactions to targeted and non-targeted chemotherapeutic drugs with emphasis on hypersensitivity responses and the invasive metastatic switch. Cancer Metastasis Rev. 32, 723-761.
Bamia, C., Lagiou, P., Buckland, G., Grioni, S., Agnoli, C., Taylor, A.J., Dahm, C.C., Overvad, K., Olsen, A., Tjønneland, A., Cottet, V., Boutron-Ruault, M.-C., Morois, S., Grote, V., Teucher, B., Boeing, H., Buijsse, B., Trichopoulos, D., Adarakis, G., Tumino, R., Naccarati, A., Panico, S., Palli, D., Bueno-de-Mesquita, H.B., van Duijnhoven, F.J.B., Peeters, P.H.M., Engeset, D., Skeie, G., Lund, E., Sánchez, M.-J., Barricarte, A., Huerta, J.-M., Ramón Quirós, J., Dorronsoro, M., Ljuslinder, I., Palmqvist, R., Drake, I., Key, T.J., Khaw, K.-T., Wareham, N., Romieu, I., Fedirko, V., Jenab, M., Romaguera, D., Norat, T., Trichopoulou, A., 2013. Mediterranean diet and colorectal cancer risk: results from a European cohort. Eur. J. Epidemiol. 28, 317-328.
Bar-Zeev, M., Livney, Y.D., Assaraf, Y.G., 2017. Targeted nanomedicine for cancer therapeutics: Towards precision medicine overcoming drug resistance. Drug Resist. Updat. 31, 15-30.
Basha, R., Connellyd, S.F., Sankpala, U.T., Purnachandra, N.G., Patel, H., Vishwanathaa, J.K., Shelakea, S., Tabor-Simecka, L., Shoji, M, Simecka, J.W., El-Rayes, B., 2016. Small molecule tolfenamic acid and dietary spice curcumin treatment enhances antiproliferative effect in pancreatic cancer cells via suppressing Sp1, disrupting NF-kB translocation to nucleus and cell cycle phase distribution. J. Nutr. Biochem. 31, 77-87.
Blois, M.S., 1958. Antioxidants determination by the use of a stable free radical. Nature. 26, 1199-1200.
Bradford, M.M., 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254.
Brahmi, F., Mechri, B., Dhibi, M., Hammami, M., 2015. Antioxidant capacity and phenolic content of olive fruits from Tunisia, extracted with different solvents. J. Plant Sci. 3, 8-12.
Buckland ,G., Travier, N., Cottet, V., González, C.A., Luján-Barroso, L., Agudo, A., Trichopoulou, A., Lagiou, P., Trichopoulos, D., Peeters, P.H., May, A., Bueno-de-Mesquita, H.B., Bvan Duijnhoven, F.J., Key, T.J., Allen, N., Khaw, K.T., Wareham, N., Romieu, I., McCormack, V., Boutron-Ruault, M., Clavel-Chapelon, F., Panico, S., Agnoli, C., Palli, D., Tumino, R., Vineis, P., Amiano, P., Barricarte, A., Rodríguez, L., Sanchez, M.J., Chirlaque, M.D., Kaaks, R., Teucher, B., Boeing, H., Bergmann, M.M., Overvad, K., Dahm, C.C., Tjønneland, A., Olsen, A., Manjer, J., Wirfält, E., Hallmans, G., Johansson, I., Lund, E., Hjartåker, A., Skeie, G., Vergnaud, A.C., Norat, T., Romaguera, D., Riboli, E., 2013. Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int. J. Cancer 132, 2918-2927.
Buckland, G, Agudo A., Luján L., Jakszyn P., Bueno-de-Mesquita, H.B., Palli, D., Boeing, H., Carneiro, F., Krogh, V., Sacerdote, C., Tumino, R., Panico, S., Nesi, G., Manjer, J., Regnér, S., Johansson, I., Stenling, R., Sanchez, M.-J., Dorronsoro, M., Barricarte, A., Navarro, C., Quirós, J.R., Allen, N.E., Key, T.J., Bingham, S., Kaaks, R., Overvad, K., Jensen, M., Olsen, A., Tjønneland, A., Peeters, P.H.M., Numans, M.E., Ocké, M.C., Clavel-Chapelon, F., Morois, S., Boutron-Ruault, M.-C., Trichopoulou, A., Lagiou, P., Trichopoulos, D., Lund, E., Couto, E., Boffeta, P., Jenab, M., Riboli, E., Romaguera, D., Mouw, T., González, C.A., 2010. Adherence to a mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Am. J. Clin. Nutr. 91, 381-390.
Caliskan, O., Polat, A.A., 2012. Effects of genotype and harvest year on phytochemical and fruit quality properties of Turkish fig genotypes. Span. J. Agric. Res. 10, 1048-1058.
Capanoglu, E., 2014. Investigating the antioxidant potential of Turkish dried fruits. Int. J. Food Prop. 17, 690-70.
Carrera-González, M.P., Ramírez-Expósito, M.J., Mayas, M.D., Martínez-Martos, J.M., 2013. Protective role of oleuropein and its metabolite hydroxytyrosol on cancer. Trends Food Sci. Technol. 31, 92-99.
Celano, M., Maggisano, V., Lepore, S.M., Russo, D., Bulotta, S., 2019. Secoiridoids of olive and derivatives as potential coadjuvant drugs in cancer: A critical analysis of experimental studies. Pharmacol. Res. 142, 77-86.
Cruz, J.M.A., Corrêa, R.F., Lamarão, C.V., Kinupp, V.F., Sanches, E.A., Campelo, P.H., Bezerra, J.A., 2022. Ficus spp. fruits: Bioactive compounds and chemical, biological and pharmacological properties. Food Res. Int. 152, 110928.
Dekdouk, N., Malafronte, N., Russo, D., Faraone, I., De Tommasi, N., Ameddah, S., Severino, L., Milella, L., 2015. Phenolic compounds from Olea europaea L. possess antioxidant activity and inhibit carbohydrate metabolizing enzymes in vitro. Evid. Based Complementary Altern. Med. 2015, 684925.
Dhar, D., Raina, K., Agarwal, R., 2018. Mechanisms and drug targets for pancreatic cancer chemoprevention. Curr. Med. Chem. 25, 2545-2565.
Eitsuka, T., Tatewaki, N., Nishida, H., Kurata, T., Nakagawa, K., Miyazawa, T., 2014. Synergistic inhibition of cancer cell proliferation with a combination of δ-tocotrienol and ferulic acid. Biochem. Biophys. Res. Commun. 453, 606-11.
Fabiani, R., De Bartolomeo, A., Rosignoli, P., Servili, M., Montedoro, G.F., Morozzi, G., 2002. Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. Eur. J. Cancer Prev. 11, 351-358.
Fahrioğlu, U., Dodurga, Y., Elmas, L., Seçme, M., 2016. Ferulic acid decreases cell viability and colony formation while inhibiting migration of MIA PaCa-2 human pancreatic cancer cells in vitro. Gene 576, 476-82.
Fki, I., Bouaziz, M., Sahnoun, Z., Sayadi, S., 2005. Hypocholesterolemic effects of phenolic-rich extracts of Chemlali olive cultivar in rats fed a cholesterol-rich diet. Bioorg. Med. Chem. 13, 5362-70.
Ghandehari, F., Fatemi, M., Avicenna, J., 2018. The effect of Ficus carica latex on 7,12-dimethylbenz (a) anthracene-induced breast cancer in rats. Avicenna Phytomed. 8, 286-295.
Gianfredi, V., Ferrara, P., Dinu, M., Nardi, M., Nucci, D., 2022. Diets, dietary patterns, single foods and pancreaticcancerrisk:anumbrellareview of meta-analyses. Int. J. Environ. Res. Public Health 19, 14787.
Goldsmith, C.D., Bond, D.R., Jankowski, H., Weidenhofer, J., Stathopoulos, C.E., Roach, P.D., Scarlett, C.J., 2018. The olive biophenols oleuropein and hydroxytyrosol selectively reduce proliferation, influence the cell cycle, and induce apoptosis in pancreatic cancer cells. Int. J. Mol. Sci. 19, 1937.
Goldsmith, C.D., Vuong, Q.V., Sadeqzadeh, E., Stathopoulos, C.E., Roach, P.D., Scarlett, C.J., 2015. Phytochemical properties and anti-proliferative activity of Olea europaea L. leaf extracts against pancreatic cancer cells. Molecules 20, 12992-13004.
Gorzynik-Debicka, M., Paulina Przychodzen, P., Cappello, F., Kuban-Jankowska, A., Gammazza, A.M., Knap, N., Wozniak, M., Gorska-Ponikowska, M., 2018. Potential health benefits of olive oil and plant polyphenols. Int. J. Mol. Sci. 19, 686.
Greenwell, M., Rahman, P.K.S.M., 2015. Medicinal plants: Their use in anticancer treatment. Int. J. Pharm. Sci. Res. 6, 4103.
Guarrera, P.M., 2005. Traditional phytotherapy in central Italy (Marche, Abruzzo, and Latium). Fitoterapia 76, 1-25.
Guasch-Ferré, M., Willett, W.C., 2021. The Mediterranean diet and health: a comprehensive overview J. Intern. Med. 290, 549-566.
Guo, Z., Jia, X., Zheng, Z, Lu, X., Zheng, Y., Zheng, B., Xiao, J., 2018. Chemical composition and nutritional function of olive (Olea europaea L.): A review. Phytochem. Rev. 17, 1091-1110.
Han, J., Talorete, T.P., Yamada, P., Isoda, H., 2009. Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells. Cytotechnology 59, 45-53.
Hashemi, S.A., Abediankenari, S., Ghasemi, M., Azadbakht, M., Yousefzadeh, Y., Dehpour, A.A., 2011. The effect of fig tree latex (Ficus carica) on stomach cancer line. Iran Red Crescent Med. J. 13, 272-5.
Hormozi, M., Marzijerani, A.S., Baharvand, P., 2020. Effects of hydroxytyrosol on expression of apoptotic genes and activity of antioxidant enzymes in LS180 cells. Cancer Manag. Res. 12, 7913-7919.
Ijoma, K.I., Ajiwe, V.I.E., Odinma, S.C., 2023. The organic extracts from the leaves of Ficus thonningii Blume, Jatropha tanjorensis J.L Ellis and Saroja and Justicia carnea Lindley as potential nutraceutical antioxidants and functional foods. Trends Phytochem. Res. 7(1), 76-85.
Kasote, D.M., Katyare, S.S., Hegde, M.V., Bae, H., 2015. Significance of antioxidant potential of plants and its relevance to therapeutic applications. Int. J. Biol. Sci. 11, 982-991.
Kazeminia, M., Mehrabi, A., Mahmoudi, R., 2022. Chemical composition, biological activities, and nutritional application of Asteraceae family herbs: A systematic review. Trends Phytochem. Res. 6(3), 187-213.
Khadhraoui, M., Bagues, M., Artés, F., Ferchichi, A., 2019. Phytochemical content, antioxidant potential, and fatty acid composition of dried Tunisian fig (Ficus carica L.) cultivars. J. Appl. Bot. Food Qual. 92, 143-150.
Khan, T., Ali, M., Khan, A., Nisar, P., Jan, S.A., Afridi, S., Shinwari, Z.K., 2019. Anticancer plants: A review of the active phytochemicals, applications in animal models, and regulatory aspects. Biomolecules 10, 47.
Kountouri, A.M., Kaliora, A.C., Koumbi, L., Andrikopoulos, N.K., 2009. In-vitro gastric cancer prevention by a polyphenol-rich extract from olives through induction of apoptosis. Eur. J. Cancer Prev. 18, 33-39.
Le, K., Chiu, F., Ng, K., 2007. Identification and quantification of antioxidants in Fructus lycii. Food Chem. 105, 353-563.
Lee, J., Kim, J.H., 2016. Kaempferol inhibits pancreatic cancer cell growth and migration through the blockade of EGFR-related pathway in vitro. PLoS ONE 11, e0155264.
LeGendre, O., Breslin, P.A.S., Foster, D.A., 2015. (-)-Oleocanthal rapidly and selectively induces cancer cell death via lysosomal membrane permeabilization. Mol. Cell. Oncol. 2, e1006077.
Li, X., Guo, S., Xiong, X.K., Peng, B.Y., Huang, J.M., Chen, M.F., Wang, F.Y., Wang, J.N., 2019. Combination of quercetin and cisplatin enhances apoptosis in OSCC cells by downregulating xIAP through the NF-κB pathway. J. Cancer 10(19), 4509-4521.
Lopez-Miranda, J., Perez-Jimenez, F., Ros, E, De Caterina, R., Badimón, L., Covas, M.I., Escrich, E., Ordovás, J.M., Soriguer, F., Abiá, R., Alarcón de la Lastra, C., Battino, M., Corella, D., Chamorro-Quirós, J., Delgado-Lista, J., Giugliano, D., Esposito, K., Estruch, R., Fernandez-Real, J.M., Gaforio, J.J., La Vecchia, C., Lairon, D., López-Segura, F., Mata, P., Menéndez, J.A., Muriana, F.J., Osada, J., Panagiotakos, D.B., Paniagua, J.A., Pérez-Martinez, P., Perona, J., Peinado, M.A., Pineda-Priego, M., Poulsen, H.E., Quiles, J.L., Ramírez-Tortosa, M.C., Ruano, J., Serra-Majem, L., Solá, R., Solanas, M., Solfrizzi, V., de la Torre-Fornell, R., Trichopoulou, A., Uceda, M., Villalba-Montoro, J.M., Villar-Ortiz, J.R., Visioli, F., Yiannakouris, N., 2010. Olive oil and health: Summary of the II international conference on olive oil and health consensus report, Jaen and Cordoba (Spain) 2008. Nutr. Metab. Cardiovasc. Dis. 20, 284-294.
Maalej, A., Bouallagui, Z., Hadrich, F., Isoda, H., Sayadi, S., 2017. Assessment of Olea europaea L. fruit extracts: Phytochemical characterization and anticancer pathway investigation. Biomed. Pharmacother. 90, 179-186.
Magalhães, L.M., Santos, M., Segundo, M.A., Reis, S., Lima, J.L.F.C., 2006. Automatic method for determination of total antioxidant capacity using 2,2-diphenyl-1-picrylhyrazyl assay. Anal. Chim. Acta. 558, 310-318.
Mahdavi, B., Mohammadhosseini, M., 2022. Antioxidant, antimicrobial and anti-prostate cancer activity of the extracts from different parts of Etlingera velutina (Ridl.) R. M. Sm (Zingiberaceae). Trends Phytochem. Res. 6(4), 353-362.
Markellos, C., Ourailidou, M.E., Gavriatopoulou, M., Halvatsiotis, P., Sergentanis, T.N., Psaltopoulou, T., 2022. Olive oil intake and cancer risk: a systematic review and meta-analysis. PLoS One 17, e0261649.
Mentella, M.C., Scaldaferri, F., Ricci, C., Gasbarrini, A., Miggiano, G.A.D., 2019. Cancer and Mediterranean diet. Nutrients. 11, 2059.
Mohammadhosseini, M., Frezza, C., Venditti, A., Akbarzadeh, A., 2019a. Ethnobotany and phytochemistry of the genus Eremostachys Bunge. Curr. Org. Chem. 23, 1828-1842.
Mohammadhosseini, M., Frezza, C., Venditti, A., Sarker, S., 2021. A systematic review on phytochemistry, ethnobotany and biological activities of the genus Bunium L. Chem. Biodivers. 18(11), e2100317.
Mohammadhosseini, M., Venditti, A., Akbarzadeh, A., 2019b. The genus Perovskia Kar.: Ethnobotany, chemotaxonomy and phytochemistry: A review. Toxin Rev. 40(4), 484-505.
Moore, M.J., Goldstein, D., Hamm, J., Figer, A., Hecht, J.R., Gallinger, S., Au, H.J., Murawa, P., Walde, D., Wolff, R.A., Campos, D., Lim, R., Ding, K., Clark, G., Voskoglou-Nomikos, T., Ptasynski, M., Parulekar, W.; National Cancer Institute of Canada Clinical Trials Group., 2007. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol. 25, 1960-1966.
Morovati, M.R., Ghanbari-Movahed, M., Barton, E.M., Farzaei, M.H., Bishayee, A., 2022. A systematic review on potential anticancer activities of Ficus carica L. with focus on cellular and molecular mechanisms. Phytomedicine 105, 154333.
Moukette, B.M., Pieme, C.A., Njimou, J.R., Biapa, C.P.N., Marco, B., Ngogang, J.Y., 2015. In vitro antioxidant properties, free radicals scavenging activities of extracts and polyphenol composition of a non-timber forest product used as spice: Monodora myristica. Evidence-Based Complement. Alternat. Med. 48, 1-17.
Mutha, R.E., Tatiya, A.U., Surana, S.J., 2021. Flavonoids as natural phenolic compounds and their role in therapeutics. Futur. J. Pharm. Sci. 7, 25.
Nguyen, L.T., Lee, Y.-H., Sharma, A.R., Park, J.-B., Jagga, S., Sharma, G., et al., 2017. Quercetin induces apoptosis and cell cycle arrest in triple-negative breast cancer cells through modulation of Foxo3a activity. Korean J. Physiol. Pharmacol. 21, 205-213.
Obafemi, F.A., Besong, E.E., 2023. A review of plants with anticancer properties. J. Clin. Med. Res. 5, 138-161.
Olaoluwa, O., Taiwo, O., Nahar, L., Sarker, S.D., 2022. Ethnopharmacology, phytochemistry and biological activities of selected African species of the genus Ficus. Trends Phytochem. Res. 6, 46-69.
Ou, A., Zhao, X., Lu, Z., 2022. Autophagy is involved in Ficus carica fruit extract-induced anti-tumor effects on pancreatic cancer. Biomed. Pharmacother. 150, 112966.
Owen, R.W., Giacosa, A., Hull, W.E., Haubner, R., Spiegelhalder, B., Bartsch, H., 2000a. The antioxidant/anticancer potential of phenolic compounds isolated from olive oil. Eur. J. Cancer. 36, 1235-1247.
Owen, R.W., Giacosa, A., Hull, W.E., Haubner, R., Würtele, G., Spiegelhalder, B., Bartsch, H., 2000b. Olive oil consumption and health: The possible role of antioxidants. Lancet Oncol. 1, 107-112.
Owen, R.W., Haubner, R., Wurtele, G., Hull, E., Spiegelhalder, B., Bartsch, H., 2004. Olives and olive oil in cancer prevention. Eur. J. Cancer Prev. 13, 319-326.
Oyaizu, M., 1986. Studies on products of browning reactions: antioxidative activities of browning reaction prepared from glucosamine. Jap. J. Nutr. 44, 307-315.
Park, W., Chawla, A., O'Reilly, E.M., 2021. Pancreatic cancer: a review. JAMA 326, 851-862.
Pei, T., Meng, Q., Han, J., Sun, H., Li, L., Song, R., Sun, B., et al., 2016. (-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma. Oncotarget. 7, 43475-43491.
Popwo Tameye, S.C., Ndom, J.C., Nguemfo, E.L., Wansi, J.D., Vardamides, J.C., Azebaze, A.G.B., 2020. Ficusanol, a new cinnamic acid derivative and other constituents from the roots of Ficus exasperata Vahl. (Moraceae) with antioxidant and cytotoxic activities. Trends Phytochem. Res. 4, 3-8.
Pourghayoumi, M., Bakhshi, D., Rahemi, M., Noroozisharaf, A., Jafari, M., Salehi, M., Chamane, R., Hernandez, F., 2017. Phytochemical attributes of some dried fig (Ficus carica L.) fruit cultivars grown in Iran. Agric. Conspec. Sci. 3, 161-166.
Purnamasari, R., Winarni, D., Permanasari, A.A., Agustina, E., Hayaza, S., Win, D., 2019. Anticancer activity of methanol extract of Ficus carica leaves and fruits against proliferation, apoptosis, and necrosis in Huh7it cells. Cancer Inform. 18, 1-7.
Rauf, A., Imran, M., Khan, I.A., Ur-Rehman, M., Gilani, S.A., Mehmood, Z., Mubarak, M.S., 2018. Anticancer potential of quercetin: A comprehensive review. Phytother. Res. 32, 2109-2130.
Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., Rice-Evans, C., 1999. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Rad. Biol. Med. 26, 1231-1237.
Romani, A., Ieri, F., Urciuoli, S., Noce, A., Marrone, G., Nediani, C., Bernini, R., 2019. Health effects of phenolic compounds found in extra-virgin olive oil, by-products, and leaf of Olea europaea L. Nutrients 11, 1776.
Saci, F., Bachir Bey, M., Louaileche, H., Gali, L., Bensouici, C., 2020. Changes in anticholinesterase, antioxidant and related bioactive compounds of carob pulp (Ceratonia siliqua L.) during ripening stage. J. Food Measur. Character. 14, 937-945.
Saha, S.K., Lee, S.B., Won, J., Choi, H.Y., Kim, K., Yang, G.-M., Dayem, A.A., Cho, S.-G., 2017. Correlation between oxidative stress, nutrition, and cancer initiation. Int. J. Mol. Sci.18, 1544.
Schwingshackl, L., Hoffmann, G., 2014. Adherence to Mediterranean diet and risk of cancer: A systematic review and meta-analysis of observational studies. Int. J. Cancer. 135, 1884-1897.
Selvarajoo, N., Stanslas, J., Islam, M.K., Sagineedu, S.R., Lian, H.K., Lim, J.C.W., 2022. Pharmacological modulation of apoptosis and autophagy in pancreatic cancer treatment. Mini Rev. Med. Chem. 22, 2581-2595.
Sepporta, M.V., Fuccelli, R., Rosignoli, P., Ricci, G., Servili, M., Morozzi G., Fabiani, R., 2014. Oleuropein inhibits tumour growth and metastases dissemination in ovariectomised nude mice with MCF-7 human breast tumour xenografts. J. Funct. Foods. 8, 269-273.
Shirazi, F.H., Piri, M., Keshavarz, S., Gholamib, S., Hosseinic, S.H., Noubaranib, M., Andalibb, S., Kamalinejad, M., Adiban, H., Eskandari, M.R., 2018. Olive fruit (Olea europaea L.): Chemopreventive effect in the rat model of hepatocellular carcinoma. PharmaNutrition 6, 207-214.
Siegel, R.L., Miller, K.D., Jemal, A., 2016. Cancer statistics. CA Cancer J. Clin. 66, 7-30.
Singh, D., Upadhyay, G., Srivastava, R.K., Shankar, S., 2015. Recent advances in pancreatic cancer: Biology, treatment, and prevention. Biochim. Biophys. Acta. 1856, 13-27.
Solomon, A.S., Golubowicz, Z., Yablowicz, S., Grossman, M., Bergman, H.E., Gottlieb, A., Altman, Z., Kerem, M.A., 2006. Antioxidant activities and anthocyanin content of fresh fruits of common fig (Ficus carica L.). J. Agric. Food Chem. 20, 7717-7723.
Soltana, H., Pinon, A., Limami, Y., Zaid, Y., Khalki, L., Zaid, N., Salah, D., Sabitaliyevich, U.Y., Simon, A., Liagre, Bertrand., Hammami, M., 2019. Antitumoral activity of Ficus carica L. on colorectal cancer cell lines. Cell. Mol. Biol. 65, 6-11.
Srivastava, R.K., Tang, S.N., Zhu, W., Meeker, D., Shankar, S., 2011. Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of pancreatic cancer stem cells. Front. Biosci. 3, 515-28.
Turkoglu, A., Duru, M.E., Mercan, N., Kivrak, I., Gezer, K., 2007. Antioxidant and antimicrobial activities of Laetiporus sulphureus (Bull.) Murrill. Food Chem. 101, 267-273.
Vendrely, V., Peuchant, E., Buscail, E., Moranvillier, I., Rousseau, B., Bedel, A., Brillac, A., de Verneuil, H., Moreau-Gaudry, F., Dabernat, S., 2017. Resveratrol and capsaicin used together as food complements reduce tumor growth and rescue full efficiency of low dose gemcitabine in a pancreatic cancer model. Cancer Lett. 390, 91-102.
Vijaya Kumar Reddy, C., Sreeramulu, D., Raghunath, M., 2010. Antioxidant activity of fresh and dry fruits commonly consumed in India. Food Res. Int. 43, 285-288.
Wang, Z., Desmoulin, S., Banerjee, S., Kong, D., Li, Y., Deraniyagala, R.L., Abbruzzese, J., Sarkar, F.H., 2008. Synergistic effects of multiple natural products in pancreatic cancer cells. Life Sci. 83, 293-300.
Xu, W., Xie, S., Chen, X., Pan, S., Qian, H., Zhu, X., 2021.Effects of quercetin on the efficacy of various chemotherapeutic drugs in cervical cancer cells. Drug Des. Devel. Ther. 15, 577-588.
Zhang, Y., Wan, Y., Huo, B., Li, B., Jin, Y., Hu, X., 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.
Zheng, J., Guinter, M.A., Merchant, A.T., Wirth, M.D., Zhang, J., Stolzenberg-Solomon, R.Z., Steck, S.E., 2017. Dietary patterns and risk of pancreatic cancer: A systematic review. Nutr. Rev. 75, 883-908.