Uptake-release by MSCs of a cationic platinum(II) complex active in vitro on human malignant cancer cell lines

Our plain-English summary of Uptake-release by MSCs of a cationic platinum(II) complex active in vitro on human malignant cancer cell lines, by I. Rimoldi, V. Coccè, G. Facchetti, et al (Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie, 2018).

The study

• Authors: I. Rimoldi, V. Coccè, G. Facchetti, G. Alessandri, A.T. Brini, F. Sisto, E. Parati, L. Cavicchini, G. Lucchini, F. Petrella, E. Ciusani, A. Pessina
• Journal: Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
• Published: 2018;108:111-118
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In this study, the in vitro stability of cisplatin (CisPt) and cationic platinum(II)-complex (caPt(II)-complex) and their in vitro activity (antiproliferative and anti-angiogenic properties) were investigated against three aggressive human tumor cell lines. caPt(II)-complex shown a high stability until 9 days of treatment and displayed a significant and higher activity than CisPt against both NCI-H28 mesothelioma (19.37 ± 9.57 μM versus 34.66 ± 7.65 μM for CisPt) and U87 MG glioblastoma (19.85 ± 0.97 μM versus 54.14 ± 3.19 for CisPt). Mesenchymal Stromal Cells (AT-MSCs) showed a significant different sensitivity (IC50 = 71.9 ± 15.1 μM for caPt(II)-complex and 8.7 ± 4.5 μM for CisPt) to the antiproliferative activity of caPt(II)-complex and CisPt. The ability of MSCs to uptake both the drugs in a similar amount of 2.49 pM /cell, suggested a possible development of new therapies based on cell mediated drug delivery.

Copyright © 2018 Elsevier Masson SAS. All rights reserved.

In plain English

This was a laboratory study of cells grown in dishes. It did not study people or asbestos exposure. The authors compared cisplatin, a standard platinum cancer drug, with a new cationic platinum(II) complex, testing both on three human cancer cell lines: NCI-H28 (malignant pleural mesothelioma), U87 MG (glioblastoma) and CFPAC-1 (pancreatic adenocarcinoma). Against the mesothelioma cells, the concentration that halved growth (IC50) was 19.37 ± 9.57 μM for the new complex and 34.66 ± 7.65 μM for cisplatin. Against glioblastoma cells it was 19.85 ± 0.97 versus 54.14 ± 3.19. Cisplatin was more active against the pancreatic cells. After 24 hours in culture medium at 37 °C, cisplatin lost its activity in a pancreatic-cell test, while the new complex kept it. Stromal cells taken from human fat absorbed similar amounts of both drugs. Over 24 hours they released 35.7% of the new complex and 95% of the cisplatin. However, fluid and extracts from these drug-loaded cells showed no anticancer activity in the tests. The authors concluded that the new complex is more active in the laboratory than cisplatin against mesothelioma and glioblastoma, and might suit cell-based drug delivery.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiments on human cell lines and cultured human cells, comparing two platinum drugs
• Who was studied: Three human tumor cell lines: malignant pleural mesothelioma NCI-H28, glioblastoma U87 MG and pancreatic adenocarcinoma CFPAC-1. Also adipose tissue mesenchymal stromal cells (AT-MSCs) isolated from lipoaspirate of adult donors (number of donors not stated), and human umbilical vein endothelial cells (HUVECs)
• Exposure: Cells were treated with cisplatin or a new cationic platinum(II) complex at a range of concentrations. Stromal cells were loaded with 75 μM of either drug for 24 h. No asbestos exposure was studied.
• Main results:
  • Against NCI-H28 mesothelioma cells, the IC50 was 19.37 ± 9.57 μM for the cationic platinum(II) complex versus 34.66 ± 7.65 μM for cisplatin (a lower value means more active)
  • Against U87 MG glioblastoma cells, the IC50 was 19.85 ± 0.97 μM for the cationic complex versus 54.14 ± 3.19 for cisplatin
  • Against CFPAC-1 pancreatic cells, cisplatin was significantly (p less than 0.01) more active: IC50 9.64 ± 5.10 μM versus 21.25 ± 6.68 μM for the cationic complex
  • Both drugs were incubated at 37 °C in complete cell culture medium, with or without a layer of stromal cells, and then tested against CFPAC-1 pancreatic cell proliferation. After 24 h, cisplatin completely lost its anticancer activity in this assay under both conditions, while the cationic complex kept activity similar to the fresh drug.
  • In tests on endothelial cells (HUVECs), the two drugs showed similar anti-angiogenic activity. After 72 h pre-incubation at 37 °C, the cationic complex kept this activity and cisplatin lost it.
  • In adipose stromal cells, 24 h cytotoxicity was similar for the two drugs: 91.1 ± 29.4 μM for the cationic complex versus 82.2 ± 54.2 μM for cisplatin. In the antiproliferation test, the IC50 differed significantly (p less than 0.05): 69.9 ± 5.5 μM for the cationic complex and 11.4 ± 5.2 μM for cisplatin.
  • Stromal cells took up amounts of the two drugs that did not differ statistically: 2.3 ± 0.11 pM/cell for the cationic complex versus 1.63 ± 0.7 pM/cell for cisplatin
  • Within 24 h, loaded stromal cells released 35.7% of the cationic complex and 95% of the cisplatin they had taken up
  • Conditioned media from drug-loaded stromal cells did not inhibit CFPAC-1 cancer cell proliferation at the doses tested. The authors attributed this to too low a drug concentration (about 2 μM).
• The authors' conclusion: The authors concluded that the cationic platinum(II) complex is more active in vitro than cisplatin against malignant pleural mesothelioma and glioblastoma. They added that its stability suggests a possible use in loading stromal cells for cell-mediated drug delivery.
• Limitations the authors state:
  • The authors state that the reason stromal cells were less sensitive to the antiproliferative effect of the cationic complex than to cisplatin is not clear and needs further investigation
  • The authors state that the reason for the different drug release by the cells is not clear
  • The amount of drug carried and released by the stromal cells in this system was too low to produce detectable inhibition of cancer cells

Topics

Medical terms in this study, explained in our Lexicon: Cisplatin, Mesothelioma.

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