There is a lot of evidence suggesting that a small subset of cancer cells resistant to conventional chemotherapy and radiotherapy and known as cancer stem cells (CSCs) is responsible for promoting metastasis and cancer relapse. Therefore, targeting and eliminating the CSCs could lead to higher survival rates and a better quality of life. In comparison with conventional chemical drugs that may not be effective against CSCs, phytochemicals are strong anti-CSCs agents. The current study examines the effect of 5-fluorouracil plus oxaliplatin (FOLFOX) as a common chemotherapy drug on colorectal cancer as well as the influence of Cinnamic acid (CINN) as a plant-derived phytochemical on colon cancer stem-like cells in HT-29 adenocarcinoma cell line.
The anti-proliferative effect of FOLFOX and CINN was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Flow cytometry analysis was used for the identification of side population (SP), CD44, and CD133 positive cells. The expression of OCT4, NANOG, ABCB1, and ALDH1A was assessed by RT-PCR.
The FOLFOX and CINN decreased cell viability in certain drug concentrations: IC50 = 5,40 μM oxaliplatin +220 μM 5-fluorouracil, and 13,50 mM for CINN. The CSC-associated markers (OCT4, NANOG, ABCB1, and ALDH1A) and the proportion of cancer stem-like cells (SP cells, CD44, and CD133 positive cells) were downregulated following the treatment of HT-29 adenocarcinoma cell line with IC50 concentrations of FOLFOX and CINN.
Our data suggests that CINN, a naturally occurring component, could be more effective than FOLFOX treatment in reducing the cancer stem-like cells and expression of CSC markers from HT-29 colon cancer cells.
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Thomas M, Coyle K, Sultan M, Vaghar-Kashani A, Marcato P. Chemoresistance in cancer stem cells and strategies to overcome resistance. Chemotherapy. 2014;3(125):2.
Blagosklonny MV. Why therapeutic response may not prolong the life of a cancer patient: selection for oncogenic resistance. Cell Cycle. 2005;4(12):1693–8.
Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res. 2009;7(3):330–8.
Hipkens J, Struck R, Gurtoo H. Role of aldehyde dehydrogenase in the metabolism-dependent biological activity of cyclophosphamide. Cancer Res. 1981;41(9 Part 1):3571–83.
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756–60.
Mathews LA, Cabarcas SM, Hurt EM, Zhang X, Jaffee EM, Farrar WL. Increased expression of DNA repair genes in invasive human pancreatic cancer cells. Pancreas. 2011;40(5):730.
Levina V, Marrangoni AM, DeMarco R, Gorelik E, Lokshin AE. Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties. PLoS One. 2008;3(8):e3077.
Guo Z, Jiang JH, Zhang J, Yang HJ, Zhong YP, Su J, et al. Side population in hepatocellular carcinoma HCCLM3 cells is enriched with stem-like cancer cells. Oncol Lett. 2016;11(5):3145–51.
Murase M, Kano M, Tsukahara T, Takahashi A, Torigoe T, Kawaguchi S, et al. Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas. Br J Cancer. 2009;101(8):1425–32.
Donnenberg VS, Landreneau RJ, Donnenberg AD. Tumorigenic stem and progenitor cells: implications for the therapeutic index of anti-cancer agents. J Control Release. 2007;122(3):385–91.
Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci U S A. 2004;101(3):781–6.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111–5.
Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67(3):1030–7.
Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423(6938):409–14.
Zhao C, Blum J, Chen A, Kwon HY, Jung SH, Cook JM, et al. Loss of β-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell. 2007;12(6):528–41.
Flahaut M, Meier R, Coulon A, Nardou K, Niggli F, Martinet D, et al. The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/β-catenin pathway. Oncogene. 2009;28(23):2245.
Ulasov IV, Nandi S, Dey M, Sonabend AM, Lesniak MS. Inhibition of sonic hedgehog and notch pathways enhances sensitivity of CD133+ glioma stem cells to temozolomide therapy. Mol Med. 2011;17(1):103.
Guo S, Liu M, Gonzalez-Perez RR. Role of notch and its oncogenic signaling crosstalk in breast cancer. Biochimica et Biophysica Acta (BBA)-reviews on. Cancer. 2011;1815(2):197–213.
Reguart N, He B, Taron M, You L, Jablons DM, Rosell R. The role of Wnt signaling in cancer and stem cells. Future Oncol. 2005;1(6):787–97.
Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med. 2006;355(12):1253–61.
Lobo NA, Shimono Y, Qian D, Clarke MF. The biology of cancer stem cells. Annu Rev Cell Dev Biol. 2007;23:675–99.
Vasiliou V, Nebert DW. Analysis and update of the human aldehyde dehydrogenase (ALDH) gene family. Hum Genomics. 2005;2(2):138.
Tanei T, Morimoto K, Shimazu K, Kim SJ, Tanji Y, Taguchi T, et al. Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential paclitaxel and epirubicin-based chemotherapy for breast cancers. Clin Cancer Res. 2009;15(12):4234–41.
Ikawa M, Impraim CC, Wang G, Yoshida A. Isolation and characterization of aldehyde dehydrogenase isozymes from usual and atypical human livers. J Biol Chem. 1983;258(10):6282–7.
Edwards BK, Ward E, Kohler BA, Eheman C, Zauber AG, Anderson RN, et al. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010;116(3):544–73.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71–96.
Park SH, Sung JY, Han S-H, Baek JH, Oh JH, Bang S-M, et al. Oxaliplatin, folinic acid and 5-fluorouracil (FOLFOX-4) combination chemotherapy as second-line treatment in advanced colorectal cancer patients with irinotecan failure: a Korean single-center experience. Jpn J Clin Oncol. 2005;35(9):531–5.
Chung SS, Vadgama JV. Curcumin and epigallocatechin gallate inhibit the cancer stem cell phenotype via down-regulation of STAT3–NFκB signaling. Anticancer Res. 2015;35(1):39–46.
Patel BB, Sengupta R, Qazi S, Vachhani H, Yu Y, Rishi AK, et al. Curcumin enhances the effects of 5-fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF-1R. Int J Cancer. 2008;122(2):267–73.
Zhang Y, Piao B, Zhang Y, Hua B, Hou W, Xu W, et al. Oxymatrine diminishes the side population and inhibits the expression of β-catenin in MCF-7 breast cancer cells. Med Oncol. 2011;28(1):99–107.
Kim JB, Ko E, Han W, Shin I, Park SY, Noh D-Y. Berberine diminishes the side population and ABCG2 transporter expression in MCF-7 breast cancer cells. Planta Med. 2008;74(14):1693–700.
Gu Y-Y, Liu L-P, Qin J, Zhang M, Chen Y, Wang D, et al. Baicalein decreases side population proportion via inhibition of ABCG2 in multiple myeloma cell line RPMI 8226 in vitro. Fitoterapia. 2014;94:21–8.
Budavari S. An encyclopedia of chemicals, drugs, and biologicals. The Merck Index. 1989;246.
Garbe D. Cinnamic Acid. In: Wiley J, editors. Ullmann’s Encyclopedia of Industrial Chemistry. Hoboken, New York: Wiley-VCH Verlag GmbH & Co. KGaA; 2000.
Lafay S, Gil-Izquierdo A. Bioavailability of phenolic acids. Phytochem Rev. 2008;7(2):301.
Clifford MN. Chlorogenic acids and other cinnamates–nature, occurrence, dietary burden, absorption and metabolism. J Sci Food Agric. 2000;80(7):1033–43.
Simonyan A. Activity of cinnamic acid derivatives and new methods for their synthesis. Pharm Chem J. 1993;27(2):92–100.
Sharma P. Cinnamic acid derivatives: a new chapter of various pharmacological activities. J Chem Pharm Res. 2011;3(2):403–23.
Narasimhan B, Belsare D, Pharande D, Mourya V, Dhake A. Esters, amides and substituted derivatives of cinnamic acid: synthesis, antimicrobial activity and QSAR investigations. Eur J Med Chem. 2004;39(10):827–34.
Carvalho SA, da Silva EF, de Souza MV, Lourenço MC, Vicente FR. Synthesis and antimycobacterial evaluation of new trans-cinnamic acid hydrazide derivatives. Bioorg Med Chem Lett. 2008;18(2):538–41.
Tonari K, Mitsui K, Yonemoto K. Structure and antibacterial activity of cinnamic acid related compounds. J Oleo Sci. 2002;51(4):271–3.
Gupta A, Soni L, Hanumantharao P, Sambasivarao S, Babu MA, Kaskhedikar S. 3D-QSAR analysis of some cinnamic acid derivatives as antimalarial agents. Asian J Chem. 2004;16(1):67.
Lee S, Han J-M, Kim H, Kim E, Jeong T-S, Lee WS, et al. Synthesis of cinnamic acid derivatives and their inhibitory effects on LDL-oxidation, acyl-CoA: cholesterol acyltransferase-1 and-2 activity, and decrease of HDL-particle size. Bioorg Med Chem Lett. 2004;14(18):4677–81.
Shahidi F, Chandrasekara A. Hydroxycinnamates and their in vitro and in vivo antioxidant activities. Phytochem Rev. 2010;9(1):147–70.
Neogi P, Lakner FJ, Medicherla S, Cheng J, Dey D, Gowri M, et al. Synthesis and structure–activity relationship studies of cinnamic acid-based novel thiazolidinedione antihyperglycemic agents. Bioorg Med Chem. 2003;11(18):4059–67.
Liu L, Hudgins WR, Shack S, Yin MQ, Samid D. Cinnamic acid: a natural product with potential use in cancer intervention. Int J Cancer. 1995;62(3):345–50.
De P, Baltas M, Bedos-Belval F. Cinnamic acid derivatives as anticancer agents-a review. Curr Med Chem. 2011;18(11):1672–703.
Sova M, Zizak Z, Stankovic JAA, Prijatelj M, Turk S, Juranic ZD, et al. Cinnamic acid derivatives induce cell cycle arrest in carcinoma cell lines. Med Chem. 2013;9(5):633–41.
de Oliveira Niero EL, Machado-Santelli GM. Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells. J Exp Clin Cancer Res. 2013;32(1):31.
Zhu B, Shang B, Li Y, Zhen Y. Inhibition of histone deacetylases by trans-cinnamic acid and its antitumor effect against colon cancer xenografts in athymic mice. Mol Med Rep. 2016;13(5):4159–66.
Pontiki E, Hadjipavlou-Litina D, Litinas K, Geromichalos G. Novel cinnamic acid derivatives as antioxidant and anticancer agents: design, synthesis and modeling studies. Molecules. 2014;19(7):9655–74.
Germann UA, Ford PJ, Shlyakhter D, Mason VS, Harding MW. Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin a, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP. Anti-Cancer Drugs. 1997;8(2):141–55.
Dantzig AH, Shepard RL, Pratt SE, Tabas LB, Lander PA, Ma L, et al. Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP-binding cassette (ABC) drug transporters. Biochem Pharmacol. 2004;67(6):1111–21.
Ford JM, Hait WN. Pharmacology of drugs that alter multidrug resistance in cancer. Pharmacol Rev. 1990;42(3):155–99.
Shudo N, Mizoguchi T, Kiyosue T, Arita M, Yoshimura A, Seto K, et al. Two pyridine analogues with more effective ability to reverse multidrug resistance and with lower calcium channel blocking activity than their dihydropyridine counterparts. Cancer Res. 1990;50(10):3055–61.
Dalerba P, Dylla SJ, Park I-K, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci. 2007;104(24):10158–63.
O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445(7123):106–10.
Wang JC, Dick JE. Cancer stem cells: lessons from leukemia. Trends Cell Biol. 2005;15(9):494–501.
Moharil RB, Dive A, Khandekar S, Bodhade A. Cancer stem cells: an insight. J Oral Maxillofac Pathol. 2017;21(3):463.
Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1(5):555–67.
Cheung A, Wan T, Leung J, Chan L, Huang H, Kwong Y, et al. Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential. Leukemia. 2007;21(7):1423–30.
Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183(4):1797–806.
Lin M-G, Liu L-P, Li C-Y, Zhang M, Chen Y, Qin J, et al. Scutellaria extract decreases the proportion of side population cells in a myeloma cell line by down-regulating the expression of ABCG2 protein. Asian Pac J Cancer Prev. 2013;14(12):7179–86.
Wu C, Alman BA. Side population cells in human cancers. Cancer Lett. 2008;268(1):1–9.
Andrews TE, Wang D, Harki DA. Cell surface markers of cancer stem cells: diagnostic macromolecules and targets for drug delivery. Drug Deliv Transl Res. 2013;3(2):121–42.
Choi YH, Yu AM. ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development. Curr Pharm. 2014;20(5):793–807.
Webb M, Raphael CL, Asbahr H, Erber WN, Meyer BF. The detection of rhodamine 123 efflux at low levels of drug resistance. Br J Haematol. 1996;93(3):650–5.
Begicevic R-R, Falasca M. ABC transporters in Cancer stem cells: beyond Chemoresistance. Int J Mol Sci. 2017;18(11):2362.
Glavinas H, Krajcsi P, Cserepes J, Sarkadi B. The role of ABC transporters in drug resistance, metabolism and toxicity. Curr Drug Deliv. 2004;1(1):27–42.
Xiong B, Ma L, Hu X, Zhang C, Cheng Y. Characterization of side population cells isolated from the colon cancer cell line SW480. Int J Oncol. 2014;45(3):1175–83.
Fukuda K, Saikawa Y, Ohashi M, Kumagai K, Kitajima M, Okano H, et al. Tumor initiating potential of side population cells in human gastric cancer. Int J Oncol. 2009;34(5):1201–7.
Hadnagy A, Gaboury L, Beaulieu R, Balicki D. SP analysis may be used to identify cancer stem cell populations. Exp Cell Res. 2006;312(19):3701–10.
Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol. 2004;5(7):738–43.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci. 2003;100(7):3983–8.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432(7015):396.
Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, et al. Characterization of clonogenic multiple myeloma cells. Blood. 2004;103(6):2332–6.
Prince M, Sivanandan R, Kaczorowski A, Wolf G, Kaplan M, Dalerba P, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci. 2007;104(3):973–8.
Plesa A, Elhamri M, Clapisson G, Mattei E, Gazzo S, Hequet O, et al. Higher percentage of CD34+ CD38− cells detected by multiparameter flow cytometry from leukapheresis products predicts unsustained complete remission in acute myeloid leukemia. Leuk Lymphoma. 2015;56(3):622–9.
Wang B-B, Li Z, Zhang F-F, Hou H-T, Yu J-K, Li F. Clinical significance of stem cell marker CD133 expression in colorectal cancer. Histol Histopathol. 2016;31:299–306.
Liu D, Sun J, Zhu J, Zhou H, Zhang X, Zhang Y. Expression and clinical significance of colorectal cancer stem cell marker EpCAMhigh/CD44+ in colorectal cancer. Oncol Lett. 2014;7(5):1544–8.
Langan RC, Mullinax JE, Raiji MT, Upham T, Summers T, Stojadinovic A, et al. Colorectal cancer biomarkers and the potential role of cancer stem cells. J Cancer. 2013;4(3):241–50.
Thenappan A, Li Y, Shetty K, Johnson L, Reddy E, Mishra L. New therapeutics targeting colon cancer stem cells. Curr Colorectal Cancer Rep. 2009;5(4):209–16.
Horst D, Kriegl L, Engel J, Kirchner T, Jung A. Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer. Cancer Investig. 2009;27(8):844–50.
Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood. 1997;90(12):5013–21.
Wang C, Xie J, Guo J, Manning HC, Gore JC, Guo N. Evaluation of CD44 and CD133 as cancer stem cell markers for colorectal cancer. Oncol Rep. 2012;28(4):1301–8.
Rizzino A. Sox2 and Oct-3/4: a versatile pair of master regulators that orchestrate the self-renewal and pluripotency of embryonic stem cells. Wiley Interdiscip Rev Syst Biol Med. 2009;1(2):228–36.
Takeda J, Seino S, Bell GI. Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. Nucleic Acids Res. 1992;20(17):4613–20.
Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003;113(5):643–55.
Huang Y, Zeng F, Xu L, Zhou J, Liu X, Le H. Anticancer effects of cinnamic acid in lung adenocarcinoma cell line h1299-derived stem-like cells. Oncol Res. 2012;20(11):499–507.
Yu Y, Kanwar SS, Patel BB, Nautiyal J, Sarkar FH, Majumdar AP. Elimination of colon cancer stem-like cells by the combination of curcumin and FOLFOX. Transl Oncol. 2009;2(4):321–8.
Nautiyal J, Kanwar SS, Yu Y, Majumdar AP. Combination of dasatinib and curcumin eliminates chemo-resistant colon cancer cells. J Mol Signal. 2011;6(1):7.
Patel BB, Gupta D, Elliott AA, Sengupta V, Yu Y, Majumdar AP. Curcumin targets FOLFOX-surviving colon cancer cells via inhibition of EGFRs and IGF-1R. Anticancer Res. 2010;30(2):319–25.
Shakibaei M, Mobasheri A, Lueders C, Busch F, Shayan P, Goel A. Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-κB and Src protein kinase signaling pathways. PLoS One. 2013;8(2):e57218.
Wang D, Kong X, Li Y, Qian W, Ma J, Wang D, et al. Curcumin inhibits bladder cancer stem cells by suppressing sonic hedgehog pathway. Biochem Biophys Res Commun. 2017;493(1):521–7.
Park S, Sung J, Chung N. Berberine diminishes side population and down-regulates stem cell-associated genes in the pancreatic cancer cell lines PANC-1 and MIA PaCa-2. Mol Cell Biochem. 2014;394(1–2):209–15.
Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci. 1997;94(19):10367–72.
Shankar S, Nall D, Tang S-N, Meeker D, Passarini J, Sharma J, et al. Resveratrol inhibits pancreatic cancer stem cell characteristics in human and Kras G12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition. PLoS One. 2011;6(1):e16530.
Shankar S, Singh G, Srivastava RK. Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Front Biosci. 2007;12:4839–54.
Zhou W, Kallifatidis G, Baumann B, Rausch V, Mattern J, Gladkich J, et al. Dietary polyphenol quercetin targets pancreatic cancer stem cells. Int J Oncol. 2010;37(3):551–61.
Kim B, Jung N, Lee S, Sohng JK, Jung HJ. Apigenin inhibits Cancer stem cell-like phenotypes in human glioblastoma cells via suppression of c-met signaling. Phytother Res. 2016;30(11):1833–40.
Erdogan S, Doganlar O, Doganlar ZB, Serttas R, Turkekul K, Dibirdik I, et al. The flavonoid apigenin reduces prostate cancer CD44+ stem cell survival and migration through PI3K/Akt/NF-κB signaling. Life Sci. 2016;162:77–86.
Erdogan S, Turkekul K, Serttas R, Erdogan Z. The natural flavonoid apigenin sensitizes human CD44+ prostate cancer stem cells to cisplatin therapy. Biomed Pharmacother. 2017;88:210–7.
Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharm Res. 2010;27(6):962–78.
Li Y, Zhang T, Korkaya H, Liu S, Lee H-F, Newman B, et al. Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res. 2010;16(9):2580–90.
Kallifatidis G, Rausch V, Baumann B, Apel A, Beckermann BM, Groth A, et al. Sulforaphane targets pancreatic tumour-initiating cells by NF-κB-induced antiapoptotic signalling. Gut. 2009;58(7):949–63.
Rausch V, Liu L, Kallifatidis G, Baumann B, Mattern J, Gladkich J, et al. Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics. Cancer Res. 2010;70(12):5004–13.
Pistollato F, Giampieri F, Battino M. The use of plant-derived bioactive compounds to target cancer stem cells and modulate tumor microenvironment. Food Chem Toxicol. 2015;75:58–70.
Scarpa E-S, Ninfali P. Phytochemicals as innovative therapeutic tools against cancer stem cells. Int J Mol Sci. 2015;16(7):15727–42.
Dandawate P, Padhye S, Ahmad A, Sarkar FH. Novel strategies targeting cancer stem cells through phytochemicals and their analogs. Drug Deliv Transl Res. 2013;3(2):165–82.
Torquato FVH, Goettert IM, Justo ZG, Paredes-Gamero JE. Anti-Cancer Phytometabolites targeting Cancer stem cells. Curr Genomics. 2017;18(2):156–74.
Taylor WF, Jabbarzadeh E. The use of natural products to target cancer stem cells. Am J Cancer Res. 2017;7(7):1588–605.
The authors thank Saeed Esmaeili Mahani at Department of Biology, Faculty of science, Shahid Bahonar University of Kerman for providing experimental equipment, Vice Chancellor for Research, Kerman University of Medical Science, Kerman, Iran for financial support.
This study was funded by Kerman University of Medical Science, Kerman, Iran (grant number: 96000157).
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The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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Soltanian, S., Riahirad, H., Pabarja, A. et al. Effect of Cinnamic acid and FOLFOX in diminishing side population and downregulating cancer stem cell markers in colon cancer cell line HT-29. DARU J Pharm Sci 26, 19–29 (2018). https://doi.org/10.1007/s40199-018-0210-8
- Colon cancer stem cells
- Side population
- Cinnamic acid
- Cancer stem cell markers