It is documented that deficient fucosylation may play an important role in the pathogenesis of cancer. Since the supplementation ofL-fucosecouldrestorefucosylationinbothin vitro and in vivoconditions,ourintentwastoexaminetheeffectofintraperitoneal administration of L-fucose and L-rhamnose (a similar deoxysaccharide) on tumour growth, mitotic activity and metastatic setting ofasolidformofEhrlichcarcinomaaswellasonthesurvivalrateoftumourbearingmice.BothL-fucoseandL-rhamnoseexerted a significant suppressive effect on tumour growth (P<0.05). After 10 days of therapy, the greatest inhibition of tumour growth expressedasapercentageofcontrolswasobservedinL-rhamnoseatadoseof3g/kg/day(by62%)andL-fucoseatadoseof 5g/kg/day(by47%).Moreover,themitoticindexdecreasedwithincreasingdosesofL-fucoseandL-rhamnose.Prolongedsurvivalof tumourbearingmicewasobservedafter14consecutivedaysofdailyadministeringL-rhamnose.Itsoptimaldosewasestimatedto be3.64g/kg/day.L-Fucose,however,displayedonlyaslighteffectonthesurvivalofthemice.OurresultssuggestthatL-fucoseand especiallyL-rhamnosehaveanticancerpotential.Thisstudyisthefirsttodemonstratethetumour-inhibitoryeffectofL-rhamnose.
Steroidal glycoalkaloids present in Solanaceae are toxic compounds biosynthesised for the protection of the plants. However, many health benefits of these compounds have been reported so far. One of their promising targets might be cancer, as demonstrated in a large number of studies. However, the main mechanism of action seems to be unclear. It could include the induction of apoptosis or trigger a necrosis with a subsequent inflammatory response. The relatively high systemic toxicity of steroidal compounds is another effect that must be taken into account in anticancer research. The main aim of this work was to summarise the recent progress in the investigation of the mechanisms of their antitumour action and to discuss their potential.
In recent years, α-tomatine has been studied for its anticancer activity. In the present study, we focused on the cytotoxic effect of α-tomatine in the MCF-7 human breast adenocarcinoma cell line, its mechanism of action, biotransformation and stability in the culture medium. We observed an inhibition of cell proliferation and viability at concentrations of 6 and 9 μM but then a recovery of cells occurred. The recovery was not caused by the biotransformation of α-tomatine in MCF-7 cells, but by a substantial decrease in the concentration of α-tomatine in the culture medium due to its binding with cholesterol. Regarding the mechanism of action of α-tomatine, we observed no DNA damage, no changes in the levels of the proteins p53 and p21WAF1/Cip1, and no apoptosis (neither activated caspase-8 and -9, nor sub-G1 peak, or morphological signs). We found a loss of ATP in α-tomatine-treated cells. These results support the conclusion that α-tomatine does not induce apoptosis in the MCF-7 cell line.
Alpha-tomatine is a major glycoalkaloid found in the roots, leaves, stems and fruit of tomatoes Lycopersiconesculentum. Recently, alpha-tomatine has been recognized as a potential anticancer drug. In the presentstudy, we identified the signaling cascades involved in the antitumor effect of alpha-tomatine on MOLT-4leukemic cells. Alpha-tomatine inhibited the proliferation and decreased the viability of MOLT-4 cells ina dose-dependent manner. An increase in the activity of caspases 9 and 3/7 was not observed. However,an increase in the amount of p53 and its phosphorylation on serine 15, as well as an increased amount ofmitochondrial protein PUMA was detected 4 and 24 h after exposure to alpha-tomatine at a concentrationof 1–3 μmol/l. Inhibition of the proliferation of MOLT-4 cells by alpha-tomatine is also associated with anincrease in p21WAF1/CIP1 and the activation of Chk2. The comet assay did not detect significant amounts ofsingle or double DNA strand breaks in cells treated with alpha-tomatine at concentrations of 0.1–9 μmol/l.Our results thus contribute to the understanding of the anticancer action of alpha-tomatine
Aim. To evaluate the anticancer effect of alpha-tomatine (i.p.) either alone or in combination with doxorubicin (i.v.) in a mouse tumour model. Methods. We studied the effect of repeated alpha-tomatine (0.1 -9 mg/kg) and/or doxorubicin (2 mg/kg) on the growth and mitotic activity of the solid Ehrlich tumour in vivo, as well as on the survival of the tumour-bearing mice. Results. Monotherapy with alpha-tomatine had a significant dose-dependent anticancer effect which peaked at 1 mg/kg. This was shown by both slowed tumour growth and reduced tumour cell proliferation. We also provide the first evidence that the combination alpha-tomatine (1 mg/kg) and doxorubicin (2 mg/kg) had a synergistic effect and significantly prolonged the survival of the mice. Neither alpha-tomatine nor doxorubicin influenced the infiltration of tumours with CD3+ lymphocytes; nor were we able to find an in vivo modulation of the key molecules of two regulatory pathways reported in vitro as the principal anti-cancer mechanisms of alpha-tomatine, i.e. iNOS and phosphorylated ERK2. However, alpha-tomatine still led to intracellular DNA inhibition and protein synthesis in Ehrlich tumour cells in a short-term culture ex vivo with IC 50 values of 8.7 and 6.6 µM. Conclusions.The results suggest that ΤΟΜ, especially in combination with doxorubicin, may be a promising agent for the treatment of malignant solid tumours. Despite growing knowledge of the mechanisms of ΤΟΜ action in cancer cells, most aspects remain unclear. Parallel organ toxicity, especially potential liver effects, requires careful attention when performing in vivo studies in the future.
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