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image of In vitro and In vivo Growth Inhibition and Apoptosis of Cancer Cells by Ethyl 4-[(4-methylbenzyl)oxy] Benzoate Complex

Abstract

Background

Cancer chemotherapy is one of the best ways to treat the patients with cancer as they can remove cancer cells, which can’t be remove by radiation or surgery.

Aims

Our study is focused on identifying potent chemotherapeutic drugs with minor or no adverse side effects. Therefore, in this study, we aimed to synthesize ethyl 4-[(4-methylbenzyl)oxy] benzoate complex, a macrocyclic aromatic compound followed by testing its antineoplastic activity against Ehrlich ascites carcinoma (EAC) human breast cancer (MCF7) cells.

Methods

and assays were used for monitoring, cytotoxicity, tumor weight, survival time, tumor cell growth inhibition, and hematological parameters to investigate the anticancer effectiveness of the tested compound. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to examine the expression of growth and apoptotic related genes. Haematological and biochemical parameters were assessed to examine the host toxicity in mice.

Results

The compound exhibited notable anticancer activity against both EAC and MCF7cells. It showed 40.70 and 58.98% cell growth inhibition at the doses of 0.5 and 1.00 mg/kg, respectively in comparison to that of control EAC-bearing mice (p < 0.0001). The result is comparable with clinically used chemotherapeutic drugs cisplatin (59.2% growth inhibition at the dose of 1.0 mg/kg body weight). A four folds reduction of tumor weight (volume) of treated group at higher dose (1.0 mg/kg/day) was noted in comparison to that of untreated EAC-bearing mice. Also, the mean survival time of treated mice (1.00 mg/kg) increased by more than 83.07% when compared to that of control EAC-bearing mice (p<0.001). In addition, EAC-bearing control mice showed drastic deterioration of RBC, WBC, and % of hemoglobin, however, in the treated mice these parameters were restored towards normal levels. A dose dependent reduction of growth and proliferation of MCF7 cells was noted in compound treated cells. Most importantly, apoptosis of MCF7 was induced followed by activation of pro-apoptotic genes () and inactivation of antiapoptotic, gene. Toxicological studies reveal that there were changes in hematological (RBC, WBC, % of Hb) and biochemical (serum glucose, cholesterol, creatinine, SGOT, SGPT) parameters during the treatment period, however, the parameters returned towards normal levels after the treatment period, indicating no or minor toxic effect of the compound on the host.

Conclusion

The compound has promising anticancer activity with no or minimum host toxic effects. Thus, it has the potential to be formulated as an effective chemo-agent, however, further preclinical and clinical research is imperative using animal and human models.

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2025-01-31
2025-03-26

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References

  1. Ma X. Yu H. Global burden of cancer. Yale J. Biol. Med. 2006 79 3-4 85 94 17940618
    [Google Scholar]
  2. Cragg G.M. Pezzuto J.M. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med. Princ. Pract. 2016 25 S2 41 59 10.1159/000443404
    [Google Scholar]
  3. Ukrainets I.V. Burian A.A. Baumer V.N. Shishkina S.V. Sidorenko L.V. Tugaibei I.A. Voloshchuk N.I. Bondarenko P.S. Synthesis, crystal structure, and biological activity of ethyl 4-methyl-2,2-dioxo-1h-2λ6,1-benzothiazine-3-carboxylate polymorphic forms. Sci. Pharm. 2018 86 2 21 10.3390/scipharm86020021 29848976
    [Google Scholar]
  4. Selvam T.P. Karthick V. Kumar P.V. Ali M.A. Synthesis and structure-activity relationship study of 2-(substituted benzylidene)-7-(4-fluorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one derivatives as anticancer agents. Drug Discov. Ther. 2012 6 4 198 204 10.5582/ddt.2012.v6.4.198 23006990
    [Google Scholar]
  5. Attalah K.M. Abdalla A.N. Aslam A. Ahmed M. Abourehab M.A.S. ElSawy N.A. Gouda A.M. Ethyl benzoate bearing pyrrolizine/indolizine moieties: Design, synthesis and biological evaluation of anti-inflammatory and cytotoxic activities. Bioorg. Chem. 2020 94 103371 10.1016/j.bioorg.2019.103371 31708230
    [Google Scholar]
  6. Hawas U.W. Abou El-Kassem L.T. Abdelfattah M.S. Elmallah M.I.Y. Eid M.A.G. Monier M.M. Marimuthu N. Cytotoxic activity of alkyl benzoate and fatty acids from the red sea sponge Hyrtios erectus. Nat. Prod. Res. 2018 32 12 1369 1374 10.1080/14786419.2017.1344662 28669229
    [Google Scholar]
  7. Wang K. Ju C. Xiao J. Chen Q. Methyl 4-(benzyloxy)-3-methoxybenzoate. Acta Crystallogr. Sect. E Struct. Rep. Online 2013 69 10 o1562 10.1107/S1600536813025415 24098242
    [Google Scholar]
  8. Liew S.K. Malagobadan S. Arshad N.M. Nagoor N.H. A review of the structure–activity relationship of natural and synthetic antimetastatic compounds. Biomolecules 2020 10 1 138 10.3390/biom10010138 31947704
    [Google Scholar]
  9. Jungwirth U. Xanthos D.N. Gojo J. Bytzek A.K. Körner W. Heffeter P. Abramkin S.A. Jakupec M.A. Hartinger C.G. Windberger U. Galanski M. Keppler B.K. Berger W. Anticancer activity of methyl-substituted oxaliplatin analogs. Mol. Pharmacol. 2012 81 5 719 728 10.1124/mol.111.077321 22331606
    [Google Scholar]
  10. Banna M.H.A. Ansary M.R.H. Miyatake R. Sheikh M.C. Zangrando E. Crystal structure of ethyl 4-[(4-methylbenzyl)oxy]benzoate. Acta Crystallogr. E Crystallogr. Commun. 2022 78 10 1077 1080 10.1107/S2056989022009380 36250124
    [Google Scholar]
  11. Islam F. Ghosh S. Khanam J.A. Antiproliferative and hepatoprotective activity of metabolites from Corynebacterium xerosis against Ehrlich Ascites Carcinoma cells. Asian Pac. J. Trop. Biomed. 2014 4 Suppl. 1 S284 S292 10.12980/APJTB.4.2014C1283 25183099
    [Google Scholar]
  12. Hassan I. Islam F. Ozeki Y. Kabir S.R. Antiproliferative activity of cytotoxic tuber lectins from Solanum tuberosum against experimentally induced Ehrlich ascites carcinoma in mice. Afr. J. Biotechnol. 2014 13 15
    [Google Scholar]
  13. Siddika A. Das P.K. Asha S.Y. Aktar S. Tareq A.R.M. Siddika A. Rakib A. Islam F. Khanam J.A. Antiproliferative activity and apoptotic efficiency of Syzygium cumini bark methanolic extract against EAC Cells In Vivo. Anticancer. Agents Med. Chem. 2021 21 6 782 792 10.2174/1871520620666200811122137 32781964
    [Google Scholar]
  14. Khatun M. Habib M.R. Rabbi M.A. Amin R. Islam M.F. Nurujjaman M. Karim M.R. Rahman M.H. Antioxidant, cytotoxic and antineoplastic effects of Carissa carandas Linn. leaves. Exp. Toxicol. Pathol. 2017 69 7 469 476 10.1016/j.etp.2017.03.008 28478952
    [Google Scholar]
  15. Yesmin R. Das P.K. Belal H. Aktar S. Siddika M.A. Asha S.Y. Habib F. Rakib M.A. Islam F. Anticancer potential of Michelia champaca Linn. bark against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. Nat. Prod. J. 2021 11 1 85 96 10.2174/2210315509666191120105647
    [Google Scholar]
  16. Yesmin R. Das P.K. Belal H. Aktar S. Ayesha M.A. Rakib M.A. Islam F. Khanam J.A. In vitro antioxidant and antidiabetic assessment of extracts from the bark of Michelia champaca, a medicinal plant in Bangladesh. World J. Pharm. Res. 2019 8 9 1505 1526
    [Google Scholar]
  17. Islam F. Gopalan V. Lam A.K.Y. Kabir S.R. Kaempferia rotunda tuberous rhizome lectin induces apoptosis and growth inhibition of colon cancer cells in vitro. Int. J. Biol. Macromol. 2019 141 775 782 10.1016/j.ijbiomac.2019.09.051 31505204
    [Google Scholar]
  18. Lee K.T.W. Islam F. Vider J. Martin J. Chruścik A. Lu C.T. Gopalan V. Lam A.K. Overexpression of family with sequence similarity 134, member B (FAM134B) in colon cancers and its tumor suppressive properties in vitro. Cancer Biol. Ther. 2020 21 10 954 962 10.1080/15384047.2020.1810535 32857678
    [Google Scholar]
  19. Mamoori A. Wahab R. Islam F. Lee K. Vider J. Lu C.T. Gopalan V. Lam A.K. Clinical and biological significance of miR-193a-3p targeted KRAS in colorectal cancer pathogenesis. Hum. Pathol. 2018 71 145 156 10.1016/j.humpath.2017.10.024 29104111
    [Google Scholar]
  20. Gopalan V. Islam F. Pillai S. Tang J.C.O. Tong D.K.H. Law S. Chan K.W. Lam A.K.Y. Overexpression of microRNA-1288 in oesophageal squamous cell carcinoma. Exp. Cell Res. 2016 348 2 146 154 10.1016/j.yexcr.2016.09.010 27658568
    [Google Scholar]
  21. Islam F. Gopalan V. Wahab R. Lee K.T. Haque M.H. Mamoori A. Lu C. Smith R.A. Lam A.K.Y. Novel FAM134B mutations and their clinicopathological significance in colorectal cancer. Hum. Genet. 2017 136 3 321 337 10.1007/s00439‑017‑1760‑4 28144752
    [Google Scholar]
  22. Islam F. Ali S.M.M. Khanam J.A. Hepatoprotective effect of acetone semicarbazone on Ehrlich ascites carcinoma induced carcinogenesis in experimental mice. Asian Pac. J. Trop. Biomed. 2013 3 2 105 110 10.1016/S2221‑1691(13)60033‑7 23593588
    [Google Scholar]
  23. Nurujjaman M. Mashhoor T. Pronoy T.U. Auwal A. Hasan M.R. Islam S.S. Hasan I. Asaduzzaman A.K. Uddin M.B. Kabir S.R. Islam F. Antitumor activity of a lectin purified from Punica granatum Pulps against Ehrlich Ascites Carcinoma (EAC) cells. Anti-Cancer Agent. Med. Chem. 2024 24 3 193 202
    [Google Scholar]
  24. Anand U. Dey A. Chandel A.K.S. Sanyal R. Mishra A. Pandey D.K. De Falco V. Upadhyay A. Kandimalla R. Chaudhary A. Dhanjal J.K. Dewanjee S. Vallamkondu J. Pérez de la Lastra J.M. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. 2023 10 4 1367 1401 10.1016/j.gendis.2022.02.007 37397557
    [Google Scholar]
  25. Negi A.S 2-benzyl-indanone compounds as anticancer agent and a process for preparation thereof. patent WO2017009860A1, 2017.
  26. Mahabalarao S.K.H. Saxena A.K. Spiro derivatives of parthenin as novel anticancer agents. Patent US8609858B2, 2009.
  27. Islam F. Khatun H. Ghosh S. Ali M.M. Khanam J.A. Bioassay of Eucalyptus extracts for anticancer activity against Ehrlich ascites carcinoma (eac) cells in Swiss albino mice. Asian Pac. J. Trop. Biomed. 2012 2 5 394 398 10.1016/S2221‑1691(12)60063‑X 23569937
    [Google Scholar]
  28. Wang X. Dong Y. Qi X. Huang C. Hou L. Cholesterol levels and risk of hemorrhagic stroke: A systematic review and meta-analysis. Stroke 2013 44 7 1833 1839 10.1161/STROKEAHA.113.001326 23704101
    [Google Scholar]
  29. Chauhan P. Yadav R. Kaushal V. Beniwal P. Evaluation of serum biochemical profile of breast cancer patients. Int. J. Med. Res. Health Sci. 2016 5 7 1
    [Google Scholar]
  30. Islam F. Khatun H. Khatun M. Ali S.M.M. Khanam J.A. Growth inhibition and apoptosis of Ehrlich ascites carcinoma cells by the methanol extract of Eucalyptus camaldulensis. Pharm. Biol. 2014 52 3 281 290 10.3109/13880209.2013.834365 24102623
    [Google Scholar]
  31. Islam F. Raihan O. Chowdhury D. Khatun M. Zuberi N. Khatun L. Brishti A. Bahar E. Apoptotic and antioxidant activities of methanol extract of Mussaenda roxburghii leaves. Pak. J. Pharm. Sci. 2015 28 6 2027 2034 26639496
    [Google Scholar]
  32. Ricci M.S. Zong W.X. Chemotherapeutic approaches for targeting cell death pathways. Oncologist 2006 11 4 342 357 10.1634/theoncologist.11‑4‑342 16614230
    [Google Scholar]
  33. Gradilone A. Gazzaniga P. Ribuffo D. Scarpa S. Cigna E. Vasaturo F. Bottoni U. Innocenzi D. Calvieri S. Scuderi N. Frati L. Aglianò A.M. Survivin, bcl-2, bax, and bcl-X gene expression in sentinel lymph nodes from melanoma patients. J. Clin. Oncol. 2003 21 2 306 312 10.1200/JCO.2003.08.066 12525523
    [Google Scholar]
  34. Yuen A.P.W. Lam K.Y. Choy J.T.H. Ho W.K. Wei W.I. The clinicopathological significance of bcl-2 expression in the surgical treatment of laryngeal carcinoma. Clin. Otolaryngol. Allied Sci. 2001 26 2 129 133 10.1046/j.1365‑2273.2001.00441.x 11309054
    [Google Scholar]
  35. Kabir S.R. Islam F. Asaduzzaman A.K.M. Biogenic silver/silver chloride nanoparticles inhibit human cancer cells proliferation in vitro and Ehrlich ascites carcinoma cells growth in vivo. Sci. Rep. 2022 12 1 8909 10.1038/s41598‑022‑12974‑z 35618812
    [Google Scholar]
  36. Green D.R. Kroemer G. Cytoplasmic functions of the tumour suppressor p53. Nature 2009 458 7242 1127 1130 10.1038/nature07986 19407794
    [Google Scholar]
  37. Li J. Yuan J. Caspases in apoptosis and beyond. Oncogene 2008 27 48 6194 6206 10.1038/onc.2008.297 18931687
    [Google Scholar]
  38. Lanvin O. Gouilleux F. Mullié C. Mazière C. Fuentes V. Bissac E. Dantin F. Mazière J.C. Régnier A. Lassoued K. Gouilleux-Gruart V. Interleukin-7 induces apoptosis of 697 pre-B cells expressing dominant-negative forms of STAT5: Evidence for caspase-dependent and -independent mechanisms. Oncogene 2004 23 17 3040 3047 10.1038/sj.onc.1207450 15048088
    [Google Scholar]
  39. Youle R.J. Strasser A. The BCL-2 protein family: Opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 2008 9 1 47 59 10.1038/nrm2308 18097445
    [Google Scholar]
  40. Tsuruo T. Naito M. Tomida A. Fujita N. Mashima T. Sakamoto H. Haga N. Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal. Cancer Sci. 2003 94 1 15 21 10.1111/j.1349‑7006.2003.tb01345.x 12708468
    [Google Scholar]
  41. Perlman H. Zhang X. Chen M.W. Walsh K. Buttyan R. An elevated bax/bcl-2 ratio corresponds with the onset of prostate epithelial cell apoptosis. Cell Death Differ. 1999 6 1 48 54 10.1038/sj.cdd.4400453 10200547
    [Google Scholar]
  42. Reyna D.E. Garner T.P. Lopez A. Kopp F. Choudhary G.S. Sridharan A. Narayanagari S.R. Mitchell K. Dong B. Bartholdy B.A. Walensky L.D. Verma A. Steidl U. Gavathiotis E. Direct activation of BAX by BTSA1 overcomes apoptosis resistance in Acute Myeloid Leukemia. Cancer Cell 2017 32 4 490 505.e10 10.1016/j.ccell.2017.09.001 29017059
    [Google Scholar]
  43. Khodapasand E. Jafarzadeh N. Farrokhi F. Kamalidehghan B. Houshmand M. Is Bax/Bcl-2 ratio considered as a prognostic marker with age and tumor location in colorectal cancer? Iran. Biomed. J. 2015 19 2 69 75 25864810
    [Google Scholar]
  44. Herceg Z. Wang Z.Q. Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat. Res. 2001 477 1-2 97 110 10.1016/S0027‑5107(01)00111‑7 11376691
    [Google Scholar]
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In vitro and In vivo Growth Inhibition and Apoptosis of Cancer Cells by Ethyl 4-[(4-methylbenzyl)oxy] Benzoate Complex
Bentham Science Publishers ; https://doi.org/10.2174/0118715206359811241227032311
/content/journals/acamc/10.2174/0118715206359811241227032311
/content/journals/acamc/10.2174/0118715206359811241227032311
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  • Article Type:     Research Article
Keywords: apoptosis ; host toxicity ; Anticancer activity ; cell growth inhibition ; survival

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