Molecular mechanisms underlying the α‑tomatine‑directed apoptosis in human malignant glioblastoma cell lines A172 and U‑118 MG

Wang, Fa‐Zhao; Dai, Xueliang; Liu, Hongyi

doi:10.3892/etm.2017.5294

Cited by 4 publications

(7 citation statements)

References 42 publications

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“…Apoptosis is regulated by key regulatory proteins of the Bcl-2 family. Most Bcl-2 family proteins play a role at the mitochondrial level, and excessive apoptosis caused by abnormal changes in the levels of Bcl-2 proteins is a key step in tumor progression [ 24 , 25 ]. Up-regulation of Bcl-2 gene expression is conducive to the inhibition of apoptosis and anti-apoptotic effect [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

Anti-Proliferation Activity of a Decapeptide from Perinereies aibuhitensis toward Human Lung Cancer H1299 Cells

et al. 2019

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Perinereis aibuhitensis peptide (PAP) is a decapeptide (Ile-Glu-Pro-Gly-Thr-Val-Gly-Met-Met-Phe, IEPGTVGMMF) with anticancer activity that was purified from an enzymatic hydrolysate of Perinereis aibuhitensis. In the present study, the anticancer effect of PAP on H1299 cell proliferation was investigated. Our results showed that PAP promoted apoptosis and inhibited the proliferation of H1299 cells in a time- and dose-dependent manner. When the PAP concentration reached 0.92 mM, more than 95% of treated cells died after 72 h of treatment. Changes in cell morphology were further analyzed using an inverted microscope and AO/EB staining and flow cytometry was adopted for detecting apoptosis and cell cycle phase. The results showed that the early and late apoptosis rates of H1299 cells increased significantly after treatment with PAP and the total apoptosis rate was significantly higher than that of the control group. Moreover, after treatment with PAP, the number of cells in the S phase of cells was significantly reduced and the ability for the cells to proliferate was also reduced. H1299 cells were arrested in the G2/M phase and cell cycle progression was inhibited. Furthermore, the results of western blotting showed that nm23-H1 and vascular endothelial growth factor (VEGF) protein levels decreased in a dose-dependent manner, while the pro-apoptotic protein and anti-apoptotic protein ratios and the level of apoptosis-related caspase protein increased in a dose-dependent manner. In conclusion, our results indicated that PAP, as a natural marine bioactive substance, inhibited proliferation and induced apoptosis of human lung cancer H1299 cells. PAP is likely to be exploited as the functional food or adjuvant that may be used for prevention or treatment of human non-small cell lung cancer in the future.

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Section: Resultsmentioning

confidence: 99%

Anti-Proliferation Activity of a Decapeptide from Perinereies aibuhitensis toward Human Lung Cancer H1299 Cells

et al. 2019

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“…Several studies have indicated that α-tomatine inhibits the growth of various human cancer cell lines within 1–48 h in a wide range of concentrations [ 20 , 21 , 22 , 23 , 24 , 25 ]. Our results show that commercial tomatine inhibited both the cell invasion and cell viability of BRAFwt and V600 BRAF metastatic melanoma cells within the range of 0.5–1 μM (expressed as α-tomatine concentration) after 24 h treatment and highlight a previously unknown ability of the bioactive compound as an antiangiogenic and vasculature-disrupting agent that is far less toxic to normal fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, Wang at al. [ 25 ] reported that α-tomatine induced ER stress and triggered both caspase-dependent and caspase-independent apoptosis. Additionally, several authors recently reported a correlation between cellular stress response, translational reprogramming, and autophagy and apoptosis induction in the presence of a persistent upstream stress condition [ 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Tomatine Displays Antitumor Potential in In Vitro Models of Metastatic Melanoma

Serratì

Porcelli

Guida

et al. 2020

IJMS

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There is a growing interest in the cytotoxic effects of bioactive glycoalkaloids, such as α-tomatine on tumor cells. Here, for the first time, we determine the antitumor potential of tomatine, a mixture of α-tomatine and dehydrotomatine, in metastatic melanoma (MM) cell lines harboring different BRAF and MC1R variants. We performed cytotoxicity experiments and annexin-V/propidium iodide staining to assess the apoptotic/necrotic status of the cells. ER stress and autophagy markers were revealed by Western Blot, whereas antiangiogenic and vascular-disrupting effects were evaluated through a capillary tube formation assay on matrigel and by ELISA kit for VEGF release determination. Cell invasion was determined by a Boyden chamber matrigel assay. Tomatine reduced 50% of cell viability and induced a concentration-dependent increase of apoptotic cells in the range of 0.5–1 μM in terms of α-tomatine. The extent of apoptosis was more than two-fold higher in V600BRAF-D184H/D184H MC1R cells than in BRAF wild-type cells and V600BRAF-MC1R wild-type cell lines. Additionally, tomatine increased the LC3I/II autophagy marker, p-eIF2α, and p-Erk1/2 levels in BRAF wild-type cells. Notably, tomatine strongly reduced cell invasion and melanoma-dependent angiogenesis by reducing VEGF release and tumor-stimulating effects on capillary tube formation. Collectively, our findings support tomatine as a potential antitumor agent in MM.

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“…α-tomatine, one of the main glycoalkaloids in tomato (Lycopersicon esculentum), has been reported to exert many beneficial effects, including biological, nutritional and pharmacological properties. Among the main activities of αtomatine, its immunological adjuvant action, antifungal and antibacterial activity, anticholesteremic effects, steroid hormone precursor status, anticancer potential, antimetastatic activity and cytostatic effect in various cancer cell lines are significant [11][12][13][14]19,[26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

“…The α-tomatine content in mature tomatoes varies from 0.03-0.06 mg α-tomatine/100 g of fresh fruit [5][6][7][8][9]. α-tomatine possesses an important antifungal, antibacterial, antiviral, antimetastatic, cell membrane lysis, LDL cholesterol reducing, immunostimulatory, apoptosis and, most importantly, antiproliferative activity [7,[10][11][12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

The α-Tomatine Exhibits Antiproliferative Activity, Rupture of Cell Membranes and Induces the Expression of APC Gene in the Human Colorectal Adenocarcinoma Cell Line (Ht-29)

Ishii

Oliveira

Mauro

et al. 2020

Braz. arch. biol. technol.

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The α-tomatine is a steroidal glycoalkaloid found in immature tomatoes (Lycopersicon esculentum) that has important biological functions including the inhibition of cancer cell growth and preventing metastasis. This study aimed to evaluate the effects of α-tomatine on cytotoxicity, cellular proliferation, apoptosis, and mRNA expression of APC, CCNA2, β-catenin, CASP9, BAK, BAX and BCL-XL in colorectal adenocarcinoma cell line HT-29. HT29 cells were treated with three concentrations of α-tomatine (0.1, 1 and 10 µg/mL), although only the 1 µg/mL concentration of α-tomatine was used to evaluate genetic expression patterns by real time-PCR. Results showed that α-tomatine was cytotoxic only at the 10 µg/mL concentration. Cell proliferation was significantly inhibited after the first 24 hours of treatment only with concentrations of 10 µg/mL. In contrast, there were no significant differences in apoptosis for any treatment. In the gene expression studies, only APC expression was significantly altered by α-tomatine treatment. In conclusion, α-HIGHLIGHTS  The α-tomatine was cytotoxic at the 10 µg/mL concentration.  The α-tomatine inhibits cell proliferation after the first 24 hours of treatment.  The α-tomatine does not induce apoptosis up to the concentration of 10 μg/mL.  The α-tomatine induces increased APC gene expression. 2 Ishhii, P.L.; et al.

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Molecular mechanisms underlying the α‑tomatine‑directed apoptosis in human malignant glioblastoma cell lines A172 and U‑118 MG

Cited by 4 publications

References 42 publications

Anti-Proliferation Activity of a Decapeptide from Perinereies aibuhitensis toward Human Lung Cancer H1299 Cells

Anti-Proliferation Activity of a Decapeptide from Perinereies aibuhitensis toward Human Lung Cancer H1299 Cells

Tomatine Displays Antitumor Potential in In Vitro Models of Metastatic Melanoma

The α-Tomatine Exhibits Antiproliferative Activity, Rupture of Cell Membranes and Induces the Expression of APC Gene in the Human Colorectal Adenocarcinoma Cell Line (Ht-29)

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