Targeting Colorectal Cancer Cells with a Functionalised Calix[4]arene Receptor: Biophysical Studies

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Jan 21

PMID 35056825

Authors

Angela F Danil de Namor

Nawal Al Hakawati

Sami Y Farhat

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer (CRC) is a disease which is causing a high degree of mortality around the world. The present study reports the antiproliferative impact of the thioacetamide calix[4]arene, CAII receptor on a highly differentiated Caco-2 cell line. This statement is corroborated by the MTT assay results which revealed a reduction in the cell viability with an IC50 value of 19.02 ± 0.04 µM. Microscopic results indicated that at the starting amount of 10 µM of CAII, a decrease in cells confluency can already be observed in addition to changes in cells morphology. Cell metabolic pathway changes were also investigated. H NMR findings showed downregulation in lactate, pyruvate, phosphocholine, lipids, and hydroxybutyrate with the upregulation of succinate, indicating a decline in the cells proliferation. Some biochemical alterations in the cells as a result of the CAII treatment were found by Raman spectroscopy.

Citing Articles

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References

Hulikova K, Grobarova V, Krivohlava R, Fiserova A . Antitumor activity of N-acetyl-D-glucosamine-substituted glycoconjugates and combined therapy with keyhole limpet hemocyanin in B16F10 mouse melanoma model. Folia Microbiol (Praha). 2010; 55(5):528-32. DOI: 10.1007/s12223-010-0087-5. View

Zhang X, Qi Z, Yin H, Yang G . Interaction between p53 and Ras signaling controls cisplatin resistance via HDAC4- and HIF-1α-mediated regulation of apoptosis and autophagy. Theranostics. 2019; 9(4):1096-1114. PMC: 6401400. DOI: 10.7150/thno.29673. View

Wong R . Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011; 30:87. PMC: 3197541. DOI: 10.1186/1756-9966-30-87. View

Lauri I, Savorani F, Iaccarino N, Zizza P, Pavone L, Novellino E . Development of an Optimized Protocol for NMR Metabolomics Studies of Human Colon Cancer Cell Lines and First Insight from Testing of the Protocol Using DNA G-Quadruplex Ligands as Novel Anti-Cancer Drugs. Metabolites. 2016; 6(1). PMC: 4812333. DOI: 10.3390/metabo6010004. View

Shurpik D, Padnya P, Stoikov I, Cragg P . Antimicrobial Activity of Calixarenes and Related Macrocycles. Molecules. 2020; 25(21). PMC: 7663816. DOI: 10.3390/molecules25215145. View

Ait Ouakrim D, Pizot C, Boniol M, Malvezzi M, Boniol M, Negri E . Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database. BMJ. 2015; 351:h4970. PMC: 4595561. DOI: 10.1136/bmj.h4970. View

Nicholson J, Wilson I . Opinion: understanding 'global' systems biology: metabonomics and the continuum of metabolism. Nat Rev Drug Discov. 2003; 2(8):668-76. DOI: 10.1038/nrd1157. View

de Boer J, Srinivas S, Park B, Pham T, Chen Z, Milner T . Polarization Effects in Optical Coherence Tomography of Various Biological Tissues. IEEE J Sel Top Quantum Electron. 2015; 5(4):1200-1204. PMC: 4358303. DOI: 10.1109/2944.796347. View

Dimilla P, Stone J, Quinn J, Albelda S, Lauffenburger D . Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength. J Cell Biol. 1993; 122(3):729-37. PMC: 2119669. DOI: 10.1083/jcb.122.3.729. View

10.

Murphy C, Harlan L, Lund J, Lynch C, Geiger A . Patterns of Colorectal Cancer Care in the United States: 1990-2010. J Natl Cancer Inst. 2015; 107(10). PMC: 4840367. DOI: 10.1093/jnci/djv198. View

11.

Halama A . Metabolomics in cell culture--a strategy to study crucial metabolic pathways in cancer development and the response to treatment. Arch Biochem Biophys. 2014; 564:100-9. DOI: 10.1016/j.abb.2014.09.002. View

12.

Arminan A, Palomino-Schatzlein M, Deladriere C, Arroyo-Crespo J, Vicente-Ruiz S, Vicent M . Metabolomics facilitates the discrimination of the specific anti-cancer effects of free- and polymer-conjugated doxorubicin in breast cancer models. Biomaterials. 2018; 162:144-153. DOI: 10.1016/j.biomaterials.2018.02.015. View

13.

Balasaheb Nimse S, Kim T . Biological applications of functionalized calixarenes. Chem Soc Rev. 2012; 42(1):366-86. DOI: 10.1039/c2cs35233h. View

14.

McConkey D . Therapy-induced apoptosis in primary tumors. Adv Exp Med Biol. 2007; 608:31-51. DOI: 10.1007/978-0-387-74039-3_3. View

15.

Zhang A, Sun H, Xu H, Qiu S, Wang X . Cell metabolomics. OMICS. 2013; 17(10):495-501. PMC: 3783970. DOI: 10.1089/omi.2012.0090. View

16.

Nicholson J, Connelly J, Lindon J, Holmes E . Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov. 2002; 1(2):153-61. DOI: 10.1038/nrd728. View

17.

den Bakker C, Schaafsma F, Huirne J, Consten E, Stockmann H, Rodenburg C . Cancer survivors' needs during various treatment phases after multimodal treatment for colon cancer - is there a role for eHealth?. BMC Cancer. 2018; 18(1):1207. PMC: 6278104. DOI: 10.1186/s12885-018-5105-z. View

18.

Robella M, Vaira M, Argenziano M, Spagnolo R, Cavalli R, Borsano A . Exploring the Use of Pegylated Liposomal Doxorubicin (Caelyx) as Pressurized Intraperitoneal Aerosol Chemotherapy. Front Pharmacol. 2019; 10:669. PMC: 6603215. DOI: 10.3389/fphar.2019.00669. View

19.

Arnold M, Sierra M, Laversanne M, Soerjomataram I, Jemal A, Bray F . Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2016; 66(4):683-691. DOI: 10.1136/gutjnl-2015-310912. View

20.

Dawn A, Yao X, Yu Y, Jiang J, Kumari H . Assessment of the toxicity of calixarenes and a metal-seamed calixarene: a chemical pathway for clinical application. Supramol Chem. 2019; 31(7):425-431. PMC: 6675036. DOI: 10.1080/10610278.2019.1616732. View