scholarly journals Antitumor efficiency of the natural alkaloid berberine complexed with C60 fullerene in Lewis lung carcinoma in vitro and in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anna Grebinyk ◽  
Svitlana Prylutska ◽  
Sergii Grebinyk ◽  
Maxim Evstigneev ◽  
Iryna Krysiuk ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Mass Spectrometry Analysis ◽  
C60 Fullerene ◽  
Lewis Lung ◽  
Tumor Weight ◽  
Molar Ratios ◽  
Natural Alkaloid

Abstract Background Berberine (Ber) is a herbal alkaloid with pharmacological activity in general and a high anticancer potency in particular. However, due to its low bioavailability, the difficulty in reaching a target and choosing the right dose, there is a need to improve approaches of Ber use in anticancer therapy. In this study, Ber, noncovalently bound to a carbon nanostructure C60 fullerene (C60) at various molar ratios of the components, was explored against Lewis lung carcinoma (LLC). Methods C60–Ber noncovalent nanocomplexes were synthesized in 1:2, 1:1 and 2:1 molar ratios. Ber release from the nanocomplexes was studied after prolonged incubation at different pH with the liquid chromatography–mass spectrometry analysis of free Ber content. Biological effects of the free and C60-complaxated Ber were studied in vitro towards LLC cells with phase-contrast and fluorescence microscopy, flow cytometry, MTT reduction, caspase activity and wound closure assays. The treatment with C60–Ber nanocomplex was evaluated in vivo with the LLC-tumored C57Bl mice. The mice body weight, tumor size, tumor weight and tumor weight index were assessed for four groups, treated with saline, 15 mg C60/kg, 7.5 mg Ber/kg or 2:1 C60-Ber nanocomplex (15 mg C60/kg, 7.5 mg Ber/kg). Results Ber release from C60–Ber nanocomplexes was promoted with medium acidification. LLC cells treatment with C60–Ber nanocomplexes was followed by enhanced Ber intracellular uptake as compared to free Ber. The cytotoxicity of the studied agents followed the order: free Ber < 1:2 < 1:1 < 2:1 C60–Ber nanocomplex. The potency of cytotoxic effect of 2:1 C60–Ber nanocomplex was confirmed by 21.3-fold decrease of IC50 value (0.8 ± 0.3 µM) compared to IC50 for free Ber (17 ± 2 µM). C60–Ber nanocomplexes induced caspase 3/7 activation and suppressed the migration activity of LLC cells. The therapeutic potency of 2:1 C60–Ber nanocomplex was confirmed in a mouse model of LLC. The tumor growth in the group treated with 2:1 C60–Ber nanocomplex is suppressed by approximately 50% at the end of experiment, while in the tumor-bearing group treated with free Ber no therapeutic effect was detected. Conclusions This study indicates that complexation of natural alkaloid Ber with C60 may be a novel therapeutic strategy against lung carcinoma. Graphical abstract

scholarly journals Nanocomplex of Berberine with C60 Fullerene Is a Potent Suppressor of Lewis Lung Carcinoma Cells Invasion In Vitro and Metastatic Activity In Vivo

Materials ◽  
2021 ◽  
Vol 14 (20) ◽  
pp. 6114
Author(s):  
Iryna Horak ◽  
Svitlana Prylutska ◽  
Iryna Krysiuk ◽  
Serhii Luhovskyi ◽  
Oleksii Hrabovsky ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Carcinoma Cells ◽  
C60 Fullerene ◽  
Lewis Lung ◽  
Invasion Potential ◽  
Lung Carcinoma Cells ◽  
Lewis Lung Carcinoma Cells

Effective targeting of metastasis is considered the main problem in cancer therapy. The development of herbal alkaloid Berberine (Ber)-based anticancer drugs is limited due to Ber’ low effective concentration, poor membrane permeability, and short plasma half-life. To overcome these limitations, we used Ber noncovalently bound to C60 fullerene (C60). The complexation between C60 and Ber molecules was evidenced with computer simulation. The aim of the present study was to estimate the effect of the free Ber and C60-Ber nanocomplex in a low Ber equivalent concentration on Lewis lung carcinoma cells (LLC) invasion potential, expression of epithelial-to-mesenchymal transition (EMT) markers in vitro, and the ability of cancer cells to form distant lung metastases in vivo in a mice model of LLC. It was shown that in contrast to free Ber its nanocomplex with C60 demonstrated significantly higher efficiency to suppress invasion potential, to downregulate the level of EMT-inducing transcription factors SNAI1, ZEB1, and TWIST1, to unblock expression of epithelial marker E-cadherin, and to repress cancer stem cells-like markers. More importantly, a relatively low dose of C60-Ber nanocomplex was able to suppress lung metastasis in vivo. These findings indicated that сomplexation of natural alkaloid Ber with C60 can be used as an additional therapeutic strategy against aggressive lung cancer.

Asian ginseng extract inhibits in vitro and in vivo growth of mouse lewis lung carcinoma via modulation of ERK-p53 and NF-κB signaling

2010 ◽  
Vol 111 (4) ◽  
pp. 899-910 ◽  
Author(s):  
Vincent Kam Wai Wong ◽  
Simon Shiu Fai Cheung ◽  
Ting Li ◽  
Zhi-Hong Jiang ◽  
Jing-Rong Wang ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Lewis Lung ◽  
Ginseng Extract ◽  
In Vivo Growth

scholarly journals Effect of Micelle-Incorporated Cisplatin With Sizes Ranging From 8 to 40 nm for the Therapy of Lewis Lung Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhicheng Wang ◽  
Yumin Li ◽  
Tong Zhang ◽  
Hongxia Li ◽  
Zhao Yang ◽  
...  
Keyword(s):  
Block Copolymers ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Drug Loading ◽  
Complexation Reaction ◽  
Lewis Lung ◽  
Antitumor Effects ◽  
Lung Carcinoma Cells

Insufficient transport of therapeutic cargo into tumor bed is a bottleneck in cancer nanomedicine. Block copolymers are promising carriers with smaller particle size by ratio modification. Here, we constructed cisplatin nanoparticles with sizes ranging from 8 to 40 nm to study the permeability and therapy of Lewis lung carcinoma. We synthesized methoxypoly(ethylene glycol)2000-block poly(L-glutamic acid sodium salt)1979 loading cisplatin through complexation reaction. The cisplatin nanomedicine has high drug loading and encapsulation efficiency. In vitro data demonstrated that cisplatin nanoparticles had equivalent growth-inhibiting effects on Lewis lung carcinoma cells compared to free cisplatin. In vivo evidences showed cisplatin nanoparticles had superior antitumor effects on the Lewis lung carcinoma mouse model with no obvious side effects. All results indicated that optimizing the ratio of block copolymers to obtain smaller sized nanomedicine could act as a promising strategy for overcoming the inadequate accumulation in poorly vascularized tumors.

DNA content distribution of in vivo and in vitro lines of Lewis lung carcinoma

1982 ◽  
Vol 18 (10) ◽  
pp. 973-978 ◽  
Author(s):  
G. Starace ◽  
G. Badaracco ◽  
C. Greco ◽  
A. Sacchi ◽  
G. Zupi
Keyword(s):  
Lung Carcinoma ◽  
Dna Content ◽  
Lewis Lung Carcinoma ◽  
Content Distribution ◽  
Lewis Lung

?-Cyclodextrin tetradecasulfate/tetrahydrocortisol�minocycline as modulators of cancer therapies in vitro and in vivo against primary and metastatic lewis lung carcinoma

1993 ◽  
Vol 33 (3) ◽  
pp. 229-238 ◽  
Author(s):  
Beverly A. Teicher ◽  
Enrique Alvarez Sotomayor ◽  
Zhen Dong Huang ◽  
Gulshan Ara ◽  
Sylvia Holden ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Cancer Therapies ◽  
Lewis Lung

In Vitro and in Vivo Selection of two Lewis Lung Carcinoma Cell Lines

1979 ◽  
Vol 65 (6) ◽  
pp. 657-664 ◽  
Author(s):  
Ada Sacchi ◽  
Anna Corsi ◽  
Marco Caputo ◽  
Gabriella Zupi
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Lung Metastases ◽  
Tumor Cell Lines ◽  
Lewis Lung ◽  
Selection Of

Two tumor cell lines adapted to grow in vitro were originated from an explant of lung metastases of Lewis lung carcinoma. These lines differ in their malignancy when reinoculated into syngeneic animals; nevertheless, they do not show any difference for their in vitro clonogenic ability. From these lines 2 in vivo sublines of 3LL carcinoma were developed. The TD 50 of the 2 in vivo sublines are different, and both the values obtained are lower than that of the original line. These results are interpreted as a selection of more malignant tumor cell lines.

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