Uptake of antitumor platinum(II)-complexes by cancer cells, assayed by inductively coupled plasma mass spectrometry (ICP-MS)

Ghezzi, AnnaRita; Aceto, Maurizio; Cassino, Claudio; Gabano, Elisabetta; Osella, Domenico

doi:10.1016/j.jinorgbio.2003.08.014

Cited by 225 publications

(180 citation statements)

References 36 publications

(81 reference statements)

Supporting

Mentioning

166

Contrasting

Unclassified

Order By: Relevance

“…Evaluating the relative cell uptake of liposomal-free platinum compounds in 8 cancer cell lines, several authors reported similar results than what was measured in our study with the F98 cells [22,23]. The lowest cell uptake was obtained after incubation with carboplatin, while an equivalent or slightly higher accumulation was reported with oxaliplatin compared to cisplatin.…”

Section: Discussionsupporting

confidence: 88%

“…The relative level of cancer cell toxicity induced by cisplatin, oxaliplatin and carboplatin measured on the F98 cells was similar to the results reported by other groups on human glioma cell lines and other cancer cell lines. The most efficient platinum compound, oxaliplatin, generally also reached the highest cell uptake [22,23,26]. Conversely, the liposomal formulations Lipoxal ™ and Lipoplatin ™ enhance the accumulation in the cancer cells but result in a lower cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

et al. 2009

View full text Add to dashboard Cite

Despite significant advances, the radiotherapy and chemotherapy protocols marginally improve the overall survival of patients with glioblastoma. Lipoplatin ™ , and Lipoxal ™ , the liposomal formulations of cisplatin and oxaliplatin respectively, were tested on the F98 glioma cells for their ability to improve the cell uptake and increase the synergic effect when combined with ionizing radiation. The cytotoxicity and synergic effect of platinum compounds were assessed by colony formation assay, while the cellular uptake was measured by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). After 4 h exposure with platinum compounds, cells were irradiated (1.5 to 6.6 Gy) with a 60 Co source. The liposomal formulations were compared to their liposome-free analogs and to carboplatin. The concomitant treatment of F98 cells with carboplatin and radiation produced the highest radiosensitizing effect (30-fold increase). Among the platinum compounds tested, Lipoplatin ™ produced the most promising results. This liposomal formulation of cisplatin improved the cell uptake by 3-fold, and its radiosensitizing potential was enhanced by 14-fold. Although Lipoxal ™ can potentially reduce the adverse effect of oxaliplatin, a synergic effect with radiation was measured only when incubated at a concentration higher than its IC50. Conversely, concomitant treatment with cisplatin did not result in a synergic effect, as in fact a radioprotective effect was measured on the F98 cells. In conclusion, among the five platinum compounds tested, carboplatin and Lipoplatin ™ showed the best radiosensitizing effect. Lipoplatin ™ seems the most promising since it led to the best cellular incorporation and has already been reported to be less neurotoxic than other platinum compounds.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

et al. 2009

View full text Add to dashboard Cite

show abstract

“…SKOV-3 or OVCAR-3 cells (1 × 10 6 ) were incubated for 24 hours with cisplatin or cisplatin + progesterone at the doses indicated for Experiment 1 (n = 6), washed with three changes of PBS, mineralized until complete drying (65% HNO 3 , 120 C), dissolved (2 ml 2% HNO 3 with indium standard), and analyzed for platinum by inductively coupled plasma mass spectrometry (ELAN 600; sensitivity = 0.1 ppb) [7].…”

Section: In Vitro Effects Of Progesterone On Cellular Platinum Accumumentioning

confidence: 99%

Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenografts

Murdoch

Kirk

Isaak

et al. 2008

Gynecologic Oncology

View full text Add to dashboard Cite

Objectives-The underlying premise of these investigations was that the lipophilic hormone progesterone, which partitions into and (at relatively high concentrations) impedes the fluid mechanics of the plasmalemma, would perturb integral associations between membrane lipids and exporter pumps that otherwise confer drug resistance. That progesterone can affect susceptibility of ovarian adenocarcinoma cells and xenografts to cisplatin was tested.Methods-The cisplatin-resistant human cell lines SKOV-3 and OVCAR-3 were treated for 24 hours with cisplatin (0.1 μg/ml) ± progesterone (0.01, 0.1 μg/ml). Cytotoxicity and platinum were measured by MTT assay and inductively coupled plasma mass spectrometry, respectively. Athymic mice were inoculated intraperitoneal (ip) with SKOV-3 cells. Cisplatin (2 mg/kg/week) ± progesterone (25 mg sustained-release pellet) regimens were initiated ip at one week (when micrometastases were present) and continued to six weeks post-xenograft. Tumor burdens, histopathology, and platinum concentrations were assessed upon necropsy at 24 hours after the final injection of cisplatin.Results-There were no significant in vitro/vivo anticancer effects of cisplatin alone. High-dose progesterone enhanced platinum accretion and induced drug toxicity in both cell lines. Tumorigenesis was suppressed by cisplatin + progesterone. The treatment synergy was related to elevated tumor platinum and morphological evidence of apoptosis.Conclusion-It appears that the addition of progesterone to ovarian cancer therapeutic modalities represents a step in improving responses.

show abstract

“…The volume of a single cell was considered to be about 2 pL. 63 Accumulation ratio 59 cell lines, including cisplatin-resistant cells. [6][7][8][9][10][11][12] In medicinal chemistry terms, their "piano-stool" structure allows the optimization of lead compounds through structureactivity relationship studies by modifying ligands around the metallic center.…”

Section: Cell Uptake In Du-145 and Hek293 Cell Linesmentioning

confidence: 99%

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

et al. 2013

View full text Add to dashboard Cite

&These two authors contributed equally to this work. ABSTRACTA straightforward methodology for the synthesis of conjugates between a cytotoxic organometallic ruthenium(II) complex and amino-and guanidinoglycosides, as potential RNA-targeted anticancer compounds, is described. Under microwave irradiation, the imidazole ligand incorporated on the aminoglycoside moiety (neamine or neomycin) was found to replace one triphenylphosphine ligand from the ruthenium precursor [(η 6 -p-cym)RuCl(PPh 3 ) 2 ] + , allowing the assembly of the target conjugates. The guanidinylated analogue was easily prepared from the neomycin-ruthenium conjugate by reaction with N,N'-di-Boc-N"-triflylguanidine, a powerful guanidinylating reagent that was compatible with the integrity of the metal complex. All conjugates were purified by semi-preparative HPLC and characterized by ESI and MALDI-TOF MS and NMR spectroscopy. The cytotoxicity of the compounds was tested in and DU-145 (prostate) human cancer cells, as well as in the normal HEK293 (Human Embryonic Kidney) cell line, revealing a dependence on the nature of the glycoside moiety and the type of cell (cancer or healthy). Indeed, neomycin-ruthenium conjugate (2) displayed moderate anti-proliferative activity in both cancer cell lines (IC 50 ≈ 80 µM), whereas that of the neamine conjugate (4) was inactive (IC 50 ≈ 200 µM).However, the guanidinylated analogue of the neomycin-ruthenium conjugate (3) required much lower concentrations than the parent conjugate for equal effect (IC 50 = 7.17 µM in DU-145 and IC 50 = 11.33 µM in MCF-7). Although the same ranking in anti-proliferative activity was found in the non-tumorigenic cell line (3 >> 2 > 4), IC 50 values indicate that aminoglycoside-containing conjugates are about 2-fold more cytotoxic in normal cells (e.g. IC 50 = 49.4 µM for 2) than in cancer cells, whereas an opposite tendency was found with the guanidinylated conjugate, since its cytotoxicity in the normal cell line (IC 50 = 12.75 µM for 3) was similar or even lower than that found in MCF-7 and DU-145 cancer cell lines, respectively. Cell uptake studies performed by ICP-MS with conjugates 2 and 3 revealed that guanidinylation of the neomycin moiety had a positive effect on accumulation (about 3-fold higher in DU-145 and 4-fold higher in HEK293), which correlates well with the higher anti-proliferative activity of 3.Interestingly, despite the slightly higher accumulation in the normal cell than in the cancer cell line (about 1.4-fold), guanidinoneomycin-ruthenium conjugate (3) was more cytotoxic to cancer cells (about 1.8-fold), whereas the opposite tendency applied for neomycin-ruthenium conjugate (2). Such differences in cytotoxic activity and cellular 3 accumulation between cancer and normal cells open the way to the creation of more selective, less toxic anticancer metallodrugs by conjugating cytotoxic metal-based complexes such as ruthenium(II) arene derivatives to guanidinoglycosides.

show abstract

Uptake of antitumor platinum(II)-complexes by cancer cells, assayed by inductively coupled plasma mass spectrometry (ICP-MS)

Cited by 225 publications

References 36 publications

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenografts

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

Contact Info

Product

Resources

About