Nitric oxide release by N-(2-chloroethyl)-N-nitrosoureas: a rarely discussed mechanistic path towards their anticancer activity

Sarkar, Amrita; Karmakar, Subhendu; Bhattacharyya, S.; Purkait, Kallol; Mukherjee, Arindam

doi:10.1039/c4ra11137k

Cited by 11 publications

(11 citation statements)

References 69 publications

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“…MCF-7 was one of the used lines in Collins et al (2012) study in which they suggest that trastuzumab can bind cells of low HER-2 level or negative and initiate antibody-dependent cell-mediated cytotoxicity [30]. Another study showed an additive interaction between trastuzumab and docetaxel or paclitaxel in HER2-weak to moderate or higher expressing cells, that may suggest that trastuzumab has a role in inhibiting her2 negative tumors by other unknown mechanism [31].…”

Section: Discussionmentioning

confidence: 99%

The effects of the nanosphere carrier for the combined carmustine-busulfan trastuzumab in human breast cancer tissue culture

Sahib¹,

Al-Dujaili²,

Abdulkadhim³

et al. 2019

ATMPH

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Cancer of the breast is from the highest cancer type's incidence. Cancer in general represents a high therapeutic challenge. Considerable adverse effects and cytotoxicity of highly potent drugs for healthy tissue require the development of novel drug delivery systems to improve pharmacokinetics and result in selective distribution of the loaded agent. Targeted therapy is a novel maneuver to achieve proper selectivity index. And as the main goal of nanocarriers is to target specific sites and improve the circulation time of the drug which is entrapped, encapsulate or conjugate in the carrier system so we chose nanoliposome as a drug carrier. Liposomes improved a potent drug targeting successfully in the last decade, but nanoliposomes offer more surface area and they have more solubility, improve controlled release, enhance bioavailability, and permit precision targeting of the material that is encapsulated to a greater extent. The Aims and objectives of the study is the formulation of HER2 Ab directed nanosphere carrier for a combined Carmustine-busulfan and trastuzumab (LCBT), then Assessing antineoplastic efficacy of (LCBT) in lung carcinoma cell line. A dose-dependent cellular growth inhibition on all three cell lines (P-value < 0.001) was seen. The concentration of 100 µg/ml of LCBT show highly significant inhibitory effect (P-value < 0.001) on cancer cell line in comparison to other concentration and other positive control drugs that forming the combination separately (P-value <0.001). The means of the half-maximal inhibitory concentration (IC50) values for LCBT combination show highly significant difference (P-value < 0.001) from other positive control groups. At the same time, the interaction indexes IAI for LCBT and for LT and LCB separately show synergistic effect that was less than one. The results of the present study also revealed a reduced expression percentages of proliferation marker Ki67 in MCF-7 cancer cell line that was treated with IC50 of LCBT and positive control (LT, LCB, T and CB) after 48 hour from drug exposure in comparison with the negative control group (P-value <0.001). Also, there was a significant decrease in expression percentages in CB containing positive control groups in comparison to T containing positive control (P-value <0.01). From the above results, we conclude that the LCBT has a prominent anticancer effect in MCF-7 breast cancer cell line as it significantly decreased the growth percentage and show apoptotic effects.

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Section: Discussionmentioning

confidence: 99%

The effects of the nanosphere carrier for the combined carmustine-busulfan trastuzumab in human breast cancer tissue culture

Sahib¹,

Al-Dujaili²,

Abdulkadhim³

et al. 2019

ATMPH

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“…Furthermore, this particular moiety exhibited significant antimicrobial activity against A. nidulans fungi . Similarly, N -nitrosoureas, a particular class of N -nitrosamines, were used as anticancer agents because of their DNA alkylation activities. , Though N -nitrosamines are not as familiar as NONOates and RSNOs, they are useful for developing photoinduced NO donors.…”

Section: No-releasing Motifs and Lmw No Donorsmentioning

confidence: 99%

Nitric Oxide Releasing Delivery Platforms: Design, Detection, Biomedical Applications, and Future Possibilities

et al. 2021

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Gasotransmitters belong to the subfamily of endogenous gaseous signaling molecules, which find a wide range of biomedical applications. Among the various gasotransmitters, nitric oxide (NO) has an enormous effect on the cardiovascular system. Apart from this, NO showed a pivotal role in neurological, respiratory, and immunological systems. Moreover, the paradoxical concentration-dependent activities make this gaseous signaling molecule more interesting. The gaseous NO has negligible stability in physiological conditions (37 °C, pH 7.4), which restricts their potential therapeutic applications. To overcome this issue, various NO delivering carriers were reported so far. Unfortunately, most of these NO donors have low stability, short half-life, or low NO payload. Herein, we review the synthesis of NO delivering motifs, development of macromolecular NO donors, their advantages/disadvantages, and biological applications. Various NO detection analytical techniques are discussed briefly, and finally, a viewpoint about the design of polymeric NO donors with improved physicochemical characteristics is predicted.

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“…Carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, C 5 H 9 Cl 2 N 3 O 2 , Figure 1, internally called “Carinamustine” due to the name of the first author) is an antineoplastic nitrosourea used in the treatment of several forms of malignant tumors, especially against leukemia and brain tumors (Weiss and Ijssel, 1982; Sarkar et al , 2015; Wang et al , 2017). Carmustine belongs to the nitrosoureas which have the cytotoxic effect of alkylating of the DNA and therefore can decelerate the growth of cancer cells by inhibiting the vital processes such as replication, transcription, and translation of DNA (Hadidi et al , 2019).…”

Section: Introductionmentioning

confidence: 99%

Crystal structure of the anticancer drug carmustine determined by X-ray powder diffraction

2021

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The structure of the anticancer drug carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, C5H9Cl2N3O2) was successfully determined from laboratory X-ray powder diffraction data recorded at 278 K and at 153 K. Carmustine crystallizes in the orthorhombic space group P212121 with Z = 4. The lattice parameters are a = 19.6935(2) Å, b = 9.8338(14) Å, c = 4.63542(6) Å, V = 897.71(2) Å³ at 153 K, and a = 19.8522(2) Å, b = 9.8843(15) Å, c = 4.69793(6) Å, V = 921.85(2) Å³ at 278 K. The Rietveld fits are very good, with low R-values and smooth difference curves of calculated and experimental powder data. The molecules form a one-dimensional hydrogen bond pattern. At room temperature, the investigated commercial sample of carmustine was amorphous.

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Nitric oxide release by N-(2-chloroethyl)-N-nitrosoureas: a rarely discussed mechanistic path towards their anticancer activity

Abstract: Our work shows that NO release is a feasible pathway of action for aromatic and heterocyclic N-(2-chloroethyl)-N-nitrosoureas and faster NO release may not lead to higher cytotoxicity.

Cited by 11 publications

References 69 publications

The effects of the nanosphere carrier for the combined carmustine-busulfan trastuzumab in human breast cancer tissue culture

The effects of the nanosphere carrier for the combined carmustine-busulfan trastuzumab in human breast cancer tissue culture

Nitric Oxide Releasing Delivery Platforms: Design, Detection, Biomedical Applications, and Future Possibilities

Crystal structure of the anticancer drug carmustine determined by X-ray powder diffraction

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