Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells

Ari, Ferda; Ertürk, Elif; Tuna, Gonca; Coskun, Demet

doi:10.14744/ejmo.2023.61594

Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells

Elif ERTÜRK, (Sağlık Hizmetleri Meslek Yüksekokulu, Bursa Uludağ Üniversitesi, Bursa, Türkiye)

Gonca TUNA, (Fen-Edebiyat Fakültesi Biyoloji Bölümü, Bursa Uludağ Üniversitesi, Bursa, Türkiye)

Demet COŞKUN, (Fen Fakültesi, Kimya Bölümü, Fırat Üniversitesi, Elazığ, Türkiye)

Ferda ARI (Fen-Edebiyat Fakültesi Biyoloji Bölümü, Bursa Uludağ Üniversitesi, Bursa, Türkiye)

Eurasian Journal of Medicine and Oncology

12 5

Yıl: 2023 Cilt: 7 Sayı: 1 Sayfa Aralığı: 24 - 33 Metin Dili: İngilizce DOI: 10.14744/ejmo.2023.61594 İndeks Tarihi: 05-05-2023

Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells

Öz:

Objectives: A member of the flavonoid family, chalcones are natural compounds known to have anticancer effects. Chalcones and their synthetic derivatives have become an important field of interest for cancer research. In this study, we aimed to investigate the anticancer activity of a new Chalcone derivative compound [(2E,4E)-1-(7-ethoxy-1-benzofuran- 2-yl)-5-(4-hydroxy-3-methoxyphenyl)penta-2,4-dien-1-one] synthesized by the Claisen-Schmidt reaction based on the curcumin structure in human lung (A549, H1299) and colon cancer (HCT116, HT29) cells. Methods: The effect of Chalcone compound on cell viability was evaluated with the SRB test. In addition, combination studies with 5-FU, which is used as a chemotherapy drug, was performed. The cell death mode was determined by fluorescence imaging method with Hoechst 33342, Annexin-V-FITC and Propidium iodide (PI) triple staining. Results: IC50 values of the Chalcone compound were found as 2.85, 1.46, 0.59, 0.35 μM for A549, H1299, HCT116, HT29, respectively. As a result of fluorescence imaging, pycnotic nuclei and chromatin condensation were observed in the cells in addition to positive staining with Annexin-V-FITC (green). Conclusion: The results showed that the newly synthesized Chalcone derivative compound has a significant cytotoxic effect on cancer cells and induce apoptosis.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. WHO. Cancer. Available at: https://www.who.int/news-room/ fact-sheets/detail/cancer. Accessed Sep 10, 2021.
2. Ashraf MA. Phytochemicals as potential anticancer drugs: time to ponder nature's bounty. Biomed Res Int 2020;2020:8602879.
3. Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012;75:311–35.
4. Guo T, Xia R, Chen M, He J, Su S, Liu L, et al. Biological activity evaluation and action mechanism of chalcone derivatives containing thiophene sulfonate. RSC Adv 2019;43:24942–50.
5. Fu Y, Liu D, Zeng H, Ren X, Song B, Hu D, et al. New chalcone derivatives: synthesis, antiviral activity and mechanism of action. RSC Adv 2020;41:24483–90.
6. Ouyang Y, Li K, Chen X, Fu X, Sun S, Wu Q. Chalcone derivatives: role in anticancer therapy. Biomolecules 2021;11:894.
7. Gaonkar SL, Vignesh UN. Synthesis and pharmacological properties of chalcones: a review. Res Chem Intermed 2017;43:6043–77.
8. Opletalova V, Hartl J, Palat KJr, Patel A. Conformational analysis of 2-hydroxy-2',5'-diazachalcones. J Pharm Biomed Anal 2000;23:55–9.
9. Batovska DI, Todorova IT. Trends in utilization of the pharmacological potential of chalcones. Curr Clin Pharmacol 2010;5:1–29.
10. Lin YM, Zhou Y, Flavin MT, Zhou LM, Nie W, Chen FC. Chalcones and flavonoids as anti-tuberculosis agents. Bioorg Med Chem 2002;10:2795–802.
11. Mahapatra DM, Bharti SK, Asati V. Anti-cancer chalcones: structural and molecular target perspectives. Eur J Med Chem 2015;98:69–114.
12. Bonakdar APS, Vafaei F, Farokhpour M, Esfahani MHN, Massah AR. Synthesis and anticancer activity assay of novel chalconesulfonamide derivatives. Iran J Pharm Res 2017;16:565–8.
13. Yang JL, Ma YH, Li YH, Zhang YP, Tian HC, Huang YC, et al. Design, synthesis, and anticancer activity of novel trimethoxyphenyl- derived chalcone-benzimidazolium salts. ACS Omega 2019;4:20381−393.
14. Coskun D, Erkisa M, Ulukaya E, Coskun MF, Ari F. Novel 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives: synthesis, characterization and anticancer activity. Eur J Med Chem 2017;18:212–22.
15. Fabianowska-Majewska K, Kaufman-Szymczyk A, Szymanska- Kolba A, Jakubik J, Majewski G, Lubecka K. Curcumin from turmeric rhizome: a potential modulator of DNA methylation machinery in breast cancer inhibition. Nutrients 2021;13:332.
16. Jin H, Qiao F, Wang Y, Xu Y, Shang Y. Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. Oncol Rep 2015;34:2782–9.
17. Tong W, Wang Q, Sun D, Sua J. Curcumin suppresses colon cancer cell invasion via AMPK-induced inhibition of NF-κB, uPA activator and MMP9. Oncol Lett 2016;12:4139–46.
18. Wang H, Zhang K, Liu J, Yang J, Tian Y, Yang C, et al. Curcumin regulates cancer progression: focus on ncRNAs and molecular signaling pathways. Front Oncol 2021;11:660712.
19. Tham CL, Lam KW, Rajajendram R, Cheah YK, Sulaiman MR, Lajis NH, et al. The effects of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone on proinflammatory signaling pathways and CLP-induced lethal sepsis in mice. Eur J Pharmacol 2011;652:136–44.
20. Sandur SK, Pandey MK, Sung B, Ahn KS, Murakatni A, Sethi G, et al. Curcumin, demethtoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis 2007;28:1765– 73.
21. Faudzi SMM, Leong SW, Abas F, Aluwi MFFM, Rullah K, Lam KW, et al. Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors. MedChemComm 2015;6:1069–80.
22. Lee KH, Aziz FHA, Syahida A, Abas F, Shaari K, Israf DA, et al. Synthesis and biological evaluation of curcumin-like diarylpentanoid analogues for anti-inflammatory, antioxidant and anti-tyrosinase activities. Eur J Med Chem 2009;44:3195–200.
23. Ari F, Erkisa M, Pekel G, Erturk E, Buyukkoroglu G, Ulukaya E. Anticancer potential of albumin bound Wnt/β-Catenin pathway inhibitor niclosamide in breast cancer cell. Chemistry Select 2021;6:7463–75.
24. Wang N, Wang Z, Peng C, You J, Shen J, Han S, et al. Dietary compound isoliquiritigenin targets GRP78 to chemosensitize breast cancer stem cells via β-catenin/ABCG2 signaling. Carcinogenesis 2014;35:2544–54.
25. Chen HY, Huang TC, Shieh TM, Wu CH, Lin LC, Hsia SM. Isoliquiritigenin induces autophagy and inhibits ovarian cancer cell growth. Int J Mol Sci 2017;18:2025.
26. Zhang B, Lai Y, Li Y, Shu N, Wang Z, Wang Y, et al. Antineoplastic activity of isoliquiritigenin, a chalcone compound, in androgen-independent human prostate cancer cells linked to G2/M cell cycle arrest and cell apoptosis. Eur J Pharmacol 2018;821:57–64.
27. Wang C, Chen Y, Wang Y, Liu X, Liu Y, Li Y, et al. Inhibition of COX-2, mPGES-1 and CYP4A by isoliquiritigenin blocks the angiogenic Akt signaling in glioma through ceRNA effect of miR- 194-5p and lncRNA NEAT1. J Exp Clin Cancer Res 2019;38:371.
28. Lin P, Chiang YF, Shieh TM, Chen HY, Shih CK, Wang TH, et al. Dietary compound isoliquiritigenin, an antioxidant from licorice, suppresses triple-negative breast tumor growth via apoptotic death program activation in cell and xenograft animal models. Antioxidants 2020;9:228.
29. Xiang S, Zeng H, Xia F, Ji Q, Xue J, Ren R, et al. The dietary flavonoid isoliquiritigenin induced apoptosis and suppressed metastasis in melanoma cells: an in vitro and in vivo study. Life Sci 2021;264:118598.
30. Li Y, Qin X, Li P, Zhang H, Lin T, Miao Z, et al. Isobavachalcone isolated from Psoralea corylifolia inhibits cell proliferation and induces apoptosis via inhibiting the AKT/GSK-3β/β-catenin pathway in colorectal cancer cells. Drug Des Devel Ther 2018;13:1449–60.
31. Di S, Fan C, Ma Z, Li M, Guo K, Han D, et al. PERK/eIF-2α/CHOP pathway dependent ROS generation mediates butein-induced non-small-cell lung cancer apoptosis and G2/M phase arrest. Int J Biol Sci 2019;15:1637–53.
32. Padhye S, Ahmad A, Oswal N, Dandawate P, Rub RA, Deshpande J, et al. Fluorinated 2′-hydroxychalcones as garcinol analogs with enhanced antioxidant and anticancer activities. Bioorg Med Chem Lett 2010;20:5818–21.
33. Gul HI, Yamali C, Gunesacar G, Sakagami H, Okudaira N, Uesawa Y, et al., Cytotoxicity, apoptosis, and QSAR studies of phenothiazine derived methoxylated chalcones as anticancer drug candidates. Med Chem Res 2018;27:2366–78.
34. Tunc D, Dere E, Karakas D, Cevatemre B, Yılmaz VT, Ulukaya E. Cytotoxic and apoptotic effects of the combination of palladium (II) 5,5-diethylbarbiturate complex with bis(2-pyridylmethyl) amine and curcumin on non small lung cancer cell lines. Bioorg Med Chem 2017;25:1717–23.
35. 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:e57218.
36. Rahim NFC, Hussin Y, Aziz MNM, Mohamad NE, Yeap SK, Masarudin MJ, et al. Cytotoxicity and apoptosis effects of curcumin analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) cyclohexanone (DMCH) on human colon cancer cells HT29 and SW620 in vitro. Molecules 2021;26:1261.
37. Gali-Muhtasib H, Hmadi R, Kareh M, Tohme R, Darwiche N. Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis. Apoptosis 2015;20:1531–62.
38. Gupta AP, Khan S, Manzoor MM, Yadav AK, Sharma G, Anand R, et al. Anticancer curcumin: natural analogues and structureactivity relationship. Stud Nat Prod Chem 2017;54:355–401.
39. Badr G, Gul HI, Yamali C, Mohamed AAM, Badr BM, Gul M, et al. Curcumin analogue 1,5-bis(4-hydroxy-3-((4-methylpiperazin- 1-yl)methyl)phenyl)penta-1,4-dien-3-one mediates growth arrest and apoptosis by targeting the PI3K/AKT/mTOR and PKC-theta signaling pathways in human breast carcinomacells. Bioorg Chem 2018;78:46–57.
40. Giacchetti S, Perpoint B, Zidani R, Bail NL, Faggiuolo R, Focan C, et al. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as firstline treatment of metastatic colorectal cancer. J Clin Oncol 2000;18:136–47.
41. Johnston PG, Kaye S. Capecitabine: a novel agent for the treatment of solid tumors. Anticancer Drugs 2001;12:639–46.
42. Sara JD, Kaur J, Khodadadi R, Rehman M, Lobo R, Chakrabarti S, et al. 5-fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol 2018;10: 1758835918780140.
43. Sethy C, Kundu CN. 5-Fluorouracil (5-FU) resistance and the new strategy to enhance the sensitivity against cancer: implication of DNA repair inhibition. Biomed Pharmacother 2021;137:111285.
44. Kurşun-Aktar BS, Oruç-Emre EE, Karaküçük-İyidoğan AK, Yağlıoğlu AŞ, Demirtaş İ, Tekin Ş. Synthesis and structureactivity relationship study: anticancer chalcones derived from 4′-morpholinoacetophenone. Marmara Pharm J 2017;21:949–60.
45. Ari F, Aztopal N, Icsel C, Yilmaz VT, Guney E, Buyukgungor O, et al. Synthesis, structural characterization and cell death-inducing effect of novel palladium(II) and platinum(II) saccharinate complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl) pyridine on cancer cells in vitro. Bioorg Med Chem 2013;21:6427–34.
46. Suwito H, Hardiyanti HD, Haq K, Kristanti AN, Furghoniyyah U, Rahmawati AN, et al. Synthesis, anticancer activity, and apoptosis mechanism of some chalcone derivatives. AIP Conference Proceedings 2020;2237:020073.
47. Zhang S, Li T, Zhang L, Wang X, Dong H, Li L, et al. A novel chalcone derivative S17 induces apoptosis through ROS dependent DR5 up-regulation in gastric cancer cells. Sci Rep 2017;7:9873.
48. Kuo YF, Su YZ, Tseng YH, Wang SY, Wang HM, Chueh PJ, et al. A novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells. Free Radic Biol Med 2010;49:214–26.
49. Kim TH, Seo WD, Ryu HW, Seo HR, Jin YB, Lee M, et al. Anti-tumor effects by a synthetic chalcone compound is mediated by c-Myc-mediated reactive oxygen species production. Chem Biol Interact 2010;188:111–8.
50. Syam S, Abdelwahab SI, Al-Mamary MA, Mohan S. Synthesis of chalcones with anticancer activities. Molecules 2012;17:6179– 95.
51. Han X, Deng S, Wang N, Liu Y, Yang X. Inhibitory effects and molecular mechanisms of tetrahydro curcumin against human breast cancer MCF-7 Cells. Food Nutr Res 2016;60:30616.
52. Hejazi J, Rastmanesh R, Taleban FA, Molana SH, Hejazi E, Ehtejab G, et al. Effect of curcumin supplementation during radiotherapy on oxidative status of patients with prostate cancer: a double blinded, randomized, placebo-controlled study. Nutr Cancer 2016;68:77–85.
53. Martínez-Castillo M, Villegas-Sepúlveda N, Meraz-Rios MA, Hernández-Zavala A, Berumen J, Coleman MA, et al., Curcumin differentially affects cell cycle and cell death in acute and chronic myeloid leukemia cells. Oncol Lett 2018;15:6777–83.
54. Zhang T, Zheng P, Shen X, Shao R, Wang B, Shen H, et al. Curcuminoid WZ26, a TrxR1 inhibitor, effectively inhibits colon cancer cell growth and enhances cisplatin-induced cell death through the induction of ROS. Free Radical Biol Med 2019;141:93–102.

APA	Ertürk E, Tuna G, Coskun D, Ari F (2023). Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells. , 24 - 33. 10.14744/ejmo.2023.61594
Chicago	Ertürk Elif,Tuna Gonca,Coskun Demet,Ari Ferda Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells. (2023): 24 - 33. 10.14744/ejmo.2023.61594
MLA	Ertürk Elif,Tuna Gonca,Coskun Demet,Ari Ferda Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells. , 2023, ss.24 - 33. 10.14744/ejmo.2023.61594
AMA	Ertürk E,Tuna G,Coskun D,Ari F Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells. . 2023; 24 - 33. 10.14744/ejmo.2023.61594
Vancouver	Ertürk E,Tuna G,Coskun D,Ari F Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells. . 2023; 24 - 33. 10.14744/ejmo.2023.61594
IEEE	Ertürk E,Tuna G,Coskun D,Ari F "Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells." , ss.24 - 33, 2023. 10.14744/ejmo.2023.61594
ISNAD	Ertürk, Elif vd. "Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells". (2023), 24-33. https://doi.org/10.14744/ejmo.2023.61594

APA	Ertürk E, Tuna G, Coskun D, Ari F (2023). Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells. Eurasian Journal of Medicine and Oncology, 7(1), 24 - 33. 10.14744/ejmo.2023.61594
Chicago	Ertürk Elif,Tuna Gonca,Coskun Demet,Ari Ferda Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells. Eurasian Journal of Medicine and Oncology 7, no.1 (2023): 24 - 33. 10.14744/ejmo.2023.61594
MLA	Ertürk Elif,Tuna Gonca,Coskun Demet,Ari Ferda Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells. Eurasian Journal of Medicine and Oncology, vol.7, no.1, 2023, ss.24 - 33. 10.14744/ejmo.2023.61594
AMA	Ertürk E,Tuna G,Coskun D,Ari F Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells. Eurasian Journal of Medicine and Oncology. 2023; 7(1): 24 - 33. 10.14744/ejmo.2023.61594
Vancouver	Ertürk E,Tuna G,Coskun D,Ari F Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells. Eurasian Journal of Medicine and Oncology. 2023; 7(1): 24 - 33. 10.14744/ejmo.2023.61594
IEEE	Ertürk E,Tuna G,Coskun D,Ari F "Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells." Eurasian Journal of Medicine and Oncology, 7, ss.24 - 33, 2023. 10.14744/ejmo.2023.61594
ISNAD	Ertürk, Elif vd. "Investigation of Anti-Cancer Activity of Newly Synthesized 2,4-pentadien-1-one Derivative Containing Benzofuran in Human Lung and Colon Cancer Cells". Eurasian Journal of Medicine and Oncology 7/1 (2023), 24-33. https://doi.org/10.14744/ejmo.2023.61594