Uptake of Ga-curcumin derivatives in different cancer cell lines: Toward the development of new potential 68 Ga-labelled curcuminoids-based radiotracers for tumour imaging

Rubagotti, Sara; Croci, Stefania; Ferrari, Érika; Orteca, Giulia; Iori, Michele; Capponi, Pier Cesare; Versari, Annibale; Asti, Mattia

doi:10.1016/j.jinorgbio.2017.05.002

Cited by 20 publications

(16 citation statements)

References 20 publications

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“…Conversely, 68 GaCl 3 , used as a negative control, demonstrated significantly lower in vitro cell uptake (20 ± 4 KBq/mg of protein after 60 min of incubation, n = 3) confirming the curcuminoid-mediated uptake by HT29 cells (Figure 6A,B). The cellular uptake of 68 Ga-DOTA-C21 is comparable to that of the compound obtained by direct labelling of curcumin with gallium-68 (i.e., 68 Ga(CUR) 2 complexes [15]), however the internalized fraction was more than doubled. To test for receptor-mediated uptake, HT29 cells were preincubated with a 200-fold excess of calcitriol, the natural ligand for vitamin D receptor (VDR), and then 68 Ga-DOTA-C21 was added.…”

Section: Resultsmentioning

confidence: 82%

“…The use of curcumin and its derivatives as potential therapeutics in many medical applications has been largely attested by a long list of scientific literature [22,23,24]. We previously demonstrated that 68 Ga-labelled curcumin complexes had preferential accumulation in HT29 colorectal cancer cells compared to other cancer cell lines and lymphocyte cultures [15]. However, the stability of these complexes in blood was low as the curcuminoid backbone was directly linked to the radio-metal through the keto-enol moiety, resulting in positively charged 2:1 ligand to metal ratio complexes.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently reported that curcuminoid complexes labelled with gallium-68 demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compare to normal human lymphocytes. In that study, the core radio-metal was directly linked to two curcuminoid molecules through the keto-enol moiety [14,15]. The curcuminoid complexes showed good stability in PBS and human serum but were rapidly degraded in whole human blood.…”

Section: Introductionmentioning

confidence: 99%

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Development of a Potential Gallium-68-Labelled Radiotracer Based on DOTA-Curcumin for Colon-Rectal Carcinoma: From Synthesis to In Vivo Studies

et al. 2019

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Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women worldwide. We have recently reported that curcuminoid complexes labelled with gallium-68 have demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compared to normal human lymphocytes. In the present study, we report a new gallium-68-labelled curcumin derivative (68Ga-DOTA-C21) and its initial validation as marker for early detection of colorectal cancer. The precursor and non-radioactive complexes were synthesized and deeply characterized by analytical methods then the curcuminoid was radiolabelled with gallium-68. The in vitro stability, cell uptake, internalization and efflux properties of the probe were studied in HT29 cells, and the in vivo targeting ability and biodistribution were investigated in mice bearing HT29 subcutaneous tumour model. 68Ga-DOTA-C21 exhibits decent stability (57 ± 3% after 120 min of incubation) in physiological media and a curcumin-mediated cellular accumulation in colorectal cancer cell line (121 ± 4 KBq of radiotracer per mg of protein within 60 min of incubation). In HT29 tumour-bearing mice, the tumour uptake of 68Ga-DOTA-C21 is 3.57 ± 0.3% of the injected dose per gram of tissue after 90 min post injection with a tumour to muscle ratio of 2.2 ± 0.2. High amount of activity (12.73 ± 1.9% ID/g) is recorded in blood and significant uptake of the radiotracer occurs in the intestine (13.56 ± 3.3% ID/g), lungs (8.42 ± 0.8% ID/g), liver (5.81 ± 0.5% ID/g) and heart (4.70 ± 0.4% ID/g). Further studies are needed to understand the mechanism of accumulation and clearance; however, 68Ga-DOTA-C21 provides a productive base-structure to develop further radiotracers for imaging of colorectal cancer.

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Section: Resultsmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of a Potential Gallium-68-Labelled Radiotracer Based on DOTA-Curcumin for Colon-Rectal Carcinoma: From Synthesis to In Vivo Studies

et al. 2019

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“…Recently, the uptake of three Ga‐curcuminoid complexes, namely, Ga (curcumin) 2+ , Ga (diacetylcurcumin, DAC) 2+ , and Ga(bis‐dehydroxycurcumin, bDHC) 2+ , was observed by the HT29‐colorectal carcinoma cell line, the K562 lymphoma cell line, and a normal fibroblast cell line. Results showed that Ga(curcumin) 2+ and Ga(DAC) 2+ exhibited a higher uptake by the HT29 and K562 cell lines than normal lymphocytes, which suggested a possible role of such complexes as potential radiotracers for tumor imaging . On the other hand, while most of the Rh complexes have shown negligible biological properties, nevertheless, the slow release of ligands without any toxicity make them ideal as drug delivery systems for compounds with cytotoxic activity and that possess poor pharmacokinetics properties, for example, curcumin.…”

Section: Anticancer Activitymentioning

confidence: 99%

Biological properties of metal complexes of curcumin

et al. 2019

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Curcumin, a naturally occurring phenolic compound isolated from Curcuma longa, has different pharmacological effects, including antiinflammatory, antimicrobial, antioxidant, and anticancer properties. However, curcumin has been found to have a limited bioavailability because of its hydrophobic nature, low-intestinal absorption, and rapid metabolism. Therefore, there is a need for enhancing the bioavailability and its solubility in water in order to increase the pharmacological effects of this bioactive compound. One strategy is curcumin complexation with transition metals to circumvent the abovementioned problems. Curcumin can undergo chelation with various metal ions to form metallo-complexes of curcumin, which may show greater effects as compared with curcumin alone. Promising results with metal curcumin complexes have been observed with regard to antioxidant, anticancer, and antimicrobial activity, as well as in treatment of Alzheimer's disease. The present review provides a concise summary of the characterization and biological properties of curcumin-metal complexes. © 2019 BioFactors, 45(3):304-317, 2019

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“…Recently several studies have shown that curcuminoids have antiageing [12], antioxidant, antimicrobial and anti-inflammatory [13], antiprotozoal [14], antivenom [15], antimalarial [16], antitumor [17], antiangiogenic [18] and anticancer [19] activities. Because of the valuable pharmacological properties of curcuminoids, evaluation of curcumin, demethoxycurcumin and bisdemethoxycurcumin of C. aeruginosa diversity in every region can guide to access appropriate selection accessions for a breeding program or direct use in commercial scale.…”

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confidence: 99%

Variability of Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin Contents in Ethanolic Extract from Ten Curcuma aeruginosa Roxb. Cultivated in West Java, Indonesia

et al. 2019

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Ten accessions of Curcuma aeruginosa Roxb. were grown under the same environment in Bogor, West Java, Indonesia was investigated for curcumin, demethoxycurcumin and bisdemethoxycurcumin contents using HPLC. No significant variations were observed among C. aeruginosa accessions for all the studied compounds. According to the results, curcumin content (mg/100 g extract) varied between 1.08 in accession Kulonprogo to 3.19 in accession Gunung Kidul. The accessions Muara Bungo and Kulonprogo had the highest (1.66) and lowest (0.51) levels of demethoxycurcumin (mg/100 g extract). Also, bisdemethoxycurcumin content varied from 0.05 to 0.49 mg/100 g extract in accessions Ciampea Bogor and Purworejo, respectively. Finally, curcuminoid contents (mg/100 g extract), accumulation of curcumin, demethoxycurcumin and bisdemethoxycurcumin contents, ranged from 1.64 to 5.05 in accessions Kulonprogo and Gunung Kidul, respectively. Hierarchical cluster analysis showed that 10 accessions could be divided into three groups. Group 1 composed of Gunung Kidul, Muara Bungo, Pakem and Beringharjo accessions. These accessions characterized by high of curcumin, demethoxycurcumin, and bisdemethoxycurcumin contents. Group 2 formed two accessions (Klewer and Purworejo) that showed the high only bisdemethoxycurcumin content. Accessions of Kulonprogo, Losari Cirebon, Madura and Ciampea Bogor, in group 3, characterized by low curcumin, demethoxycurcumin and bisdemethoxycurcumin contents. In this study, Gunung Kidul, Muara Bungo, Pakem and Beringharjo accessions have a high in curcuminoid content that showed a high potential for use in future plant breeding programs.

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Uptake of Ga-curcumin derivatives in different cancer cell lines: Toward the development of new potential 68 Ga-labelled curcuminoids-based radiotracers for tumour imaging

Cited by 20 publications

References 20 publications

Development of a Potential Gallium-68-Labelled Radiotracer Based on DOTA-Curcumin for Colon-Rectal Carcinoma: From Synthesis to In Vivo Studies

Development of a Potential Gallium-68-Labelled Radiotracer Based on DOTA-Curcumin for Colon-Rectal Carcinoma: From Synthesis to In Vivo Studies

Biological properties of metal complexes of curcumin

Variability of Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin Contents in Ethanolic Extract from Ten Curcuma aeruginosa Roxb. Cultivated in West Java, Indonesia

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