Organotin compounds as effective antimetastatic substances in the treatment of epidermoid lung carcinoma Lewis (LLC) in an experiment.

e15054 Background: Lung cancer occupies one of the first places in the structure of oncological diseases in the world. Reducing the life expectancy of patients, as a rule, occurs as a result of metastatic complications, so the search for new antimetastatic agents is an urgent task for experimental pharmacology and oncology. The aim of our study is to assess the severity of metastatic lesion in the Lewis lung epidermoid carcinoma (LLC) model in the presence of an organotin compound. Methods: The study was conducted on experimental C57BL/6 mice (n = 24, each group contained 12 mice) with LLC (subcutaneous transplantation) in the presence of the cytotoxic organotin compound 2,6-bis (1,1-dimethylethyl) - 4 - [(triphenylstannyl)thio]phenol (Me5). All manipulations were carried out in accordance with the European Convention for the Protection of Vertebrates Used for Experimental and Other Scientific Purposes (ETS 123). Female mice (8 weeks of age, weighing 21-22 g) were intraperitoneally injected with a 1% aqueous gelatin solution of organotin Me5 daily for 5 days. The most effective total dose of Me5 was 250 mg / kg. The animals of the control group received saline solution in similar modes and volumes. In the experimental and control groups, the degree of metastatic lesion was assessed on the 21-day post-grafting period according to the scale proposed by D. Tarin and J. E. Price, which allows us to differentiate the severity of the lesion depending on the number of metastases and their size. The experiment describes three degrees of lesion: LCP-1 (metastases less than 10 pcs. with a diameter not exceeding 1 mm); LCP-2 (metastases from 10 to 30 pieces, some of them larger than 1 mm) and HCP-3 (metastases larger than 30 pieces of different sizes, but no drain). The pathohistological structure was studied by the light-optical method with hematoxylin and eosin staining. Results: When administered intraperitoneal to mice, Me5 did not inhibit the growth of the primary tumor site in the experimental group, but significantly reduced the severity of metastatic lesions in the lungs. In the control group, 75 % of mice with LLC had LCP - 2 (low colonization potential) and in 25% of HCP-3 (high colonization potential) metastatic lesions, in the experimental group only mild lesions were noted in all animals: 58% of mice had LCP – 1, 42% - LCP-2. Conclusions: It is concluded that the overall result of this study clearly demonstrates that the organotin compound 2,6-bis (1,1-dimethylethyl) - 4 - [(triphenylstannyl)thio] phenol (Me5) is an effective antimetastatic agent in the Lewis lung epidermoid carcinoma (LLC) model at a total dose of 250 mg/kg.

An Evaluation of the Anti-Carcinogenic Response of Major Isothiocyanates in Non-Metastatic and Metastatic Melanoma Cells

Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocyanates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells. Our aim was to compare different endpoints of cytotoxicity (e.g., reactive oxygen species, intracellular glutathione content, cell cycle growth arrest, apoptosis and necrosis) descriptive of an anti-cancer response between non-metastatic and metastatic melanoma as well as non-melanoma epidermoid carcinoma and non-tumorigenic cells. Our results showed that exposure to isothiocyanates induced an increase in intracellular reactive oxygen species and glutathione contents between non-metastatic and metastatic melanoma cells. The distribution of cell cycle phases followed a similar pattern in a manner where non-metastatic and metastatic melanoma cells appeared to be growth arrested at the G2/M phase while elevated levels of metastatic melanoma cells were shown to be at sub G1 phase, an indicator of necrotic cell death. Finally, metastatic melanoma cells were more sensitive apoptosis and/or necrosis as higher levels were observed compared to non-melanoma epidermoid carcinoma and non-tumorigenic cells. In general, non-melanoma epidermoid carcinoma and non-tumorigenic cells were more resistant under any experimental exposure condition. Overall, our study provides further evidence for the potential development of isothiocyanates as promising anti-cancer agents against non-metastatic and metastatic melanoma cells, a property specific for these cells and not shared by non-melanoma epidermoid carcinoma or non-tumorigenic melanocyte cells.