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Chemotherapeutic Response to Cisplatin-like Drugs in Human Breast Cancer Cells Probed by Vibrational Microspectroscopy

DOI: 10.1039/C5FD00148J DOI Help

Authors: Ana L. M. Batista De Carvalho (University of Coimbra) , Mike Pilling (University of Manchester) , Peter Gardner (University of Manchester) , James Doherty (University of Manchester) , Gianfelice Cinque (Diamond Light Source) , Katia Wehbe (Diamond Light Source) , Chris Kelley (Diamond Light Source) , Luis Batista De Carvalho (University of Coimbra) , Maria Paula M Marques (University of Coimbra)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Faraday Discussions , VOL 187 , PAGES 273 – 298

State: Published (Approved)
Published: January 2016
Diamond Proposal Number(s): 10065

Abstract: Studies of drug-cell interactions in cancer model systems are essential in the preclinical stage of rational drug design, which relies on a thorough understanding of the mechanisms underlying cytotoxic activiy and biological effects, at a molecular level. This study aimed at applying complementary vibrational spectroscopy methods to evaluate the cellular impact of two Pt(II) and Pd(II) dinuclear chelates with spermine (Pt2Spm and Pd2Spm), using cisplatin (cis-Pt(NH3)2Cl2) as a reference compound. Their effects on cellular metabolism were monitored in a human triple-negative metastatic breast cancer cell line (MDA-MB-231) by Raman and synchrotron-radiation infrared microspectroscopies, for different drug concentrations (2-8 μM) at 48 h exposure. Multivariate data analysis was applied (unsupervised PCA), unveiling drug- and concentration-dependent effects: apart from discrimination between control and drug-treated cells, a clear separation was obtained for the different agents studied – mononuclear vs polynuclear, and Pt(II) vs Pd(II). Spectral biomarkers of drug action were identified, as well as the cellular response to the chemotherapeutic insult. The main effect of the tested compounds was found to be on DNA, lipids and proteins, the Pd(II) agent having a more significant impact on proteins while its Pt(II) homologue affected the cellular lipid content at lower concentrations, which suggests the occurrence of distinct and unconventional pathways of cytotoxicity for these dinuclear polyamine complexes. Raman and FTIR microspectroscopies were confirmed as powerful non-invasive techniques to obtain unique spectral signatures of biochemical impact and physiological reaction of cells to anticancer agents.

Journal Keywords: Cancer; Breast cancer; FTIR microspectroscopy

Subject Areas: Chemistry, Medicine


Instruments: B22-Multimode InfraRed imaging And Microspectroscopy

Other Facilities: STFC (UK), for access to neutron beam facilities (RB 520092, 1320035)