α-Tomatine, a novel early-stage autophagy inhibitor, inhibits autophagy to enhance apoptosis via Beclin-1 in Skov3 cells

Wu, Hailun; Li, Weibin; Wang, Tingting; Yan, Rong; He, Ziying; Huang, Si-Ting; Zhang, Lifan; Wu, Zuoxing; Liu, Chanzhen

doi:10.1016/j.fitote.2021.104911

Cited by 20 publications

(12 citation statements)

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“…Recently published evidence suggests that tomatine presents antitumor activity, as demonstrated by several in vitro and in vivo studies (Faria-Silva et al, 2022). For instance, in vitro studies have shown that tomatine is highly effective in inhibiting the growth of human cancer cell lines of the breast (Choi et al, 2012;Shi et al, 2013), colon (Kim et al, 2015;Rudolf and Rudolf, 2016), gastric (Xiuwei et al, 2007;Choi et al, 2012), hepatocellular (Xiuwei et al, 2007;Del Giudice et al, 2015), prostate (Choi et al, 2012;Huang et al, 2015), and ovarian (Wu et al, 2021) among others. At the same time, in vivo experiments indicate carcinomas that tomatine showed great antitumor potential in mice mammary adenocarcinoma (Tomsik et al, 2013), and HL60 xenograft tumor (Chao et al, 2012); in rainbow trout stomach tumors (Friedman et al, 2007); and subcutaneous and orthotopic xenograft tumors of human prostate cancer PC-3 cells (Lee et al, 2013a;Lee et al, 2013b, Lee et al, 2022.…”

Section: Introductionmentioning

confidence: 99%

In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma

et al. 2022

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Background: There is abundant ethnopharmacological evidence the uses of regarding Solanum species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species.Purpose: To evaluate the anticancer effect of the Solanum glycoalkaloid tomatine in hepatocellular carcinoma (HCC) in vitro (HepG2 cells) and in vivo models.Methods: The resazurin reduction assay was performed to detect the effect of tomatine on cell viability in human HepG2 cell lines. Programmed cell death was investigated by means of cellular apoptosis assays using Annexin V. The expression of cancer related proteins was detected by Western blotting (WB). Reactive oxygen species (ROS) and calcium were determined by 2,7-dichlorodihydrofluorescein diacetate and Fluo-4, respectively. Intrahepatic HepG2 xenograft mouse model was used to elucidate the effect of tomatine on tumor growth in vivo.Results and Discussion: Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death, consistently with caspase-3, -7, Bcl-2 family, and P53 proteins activation. Furthermore, tomatine increased intracellular ROS and cytosolic Ca+2 levels. Moreover, the NSG mouse xenograft model showed that treating mice with tomatine inhibited HepG2 tumor growth.Conclusion: Tomatine inhibits in vitro and in vivo HCC tumorigenesis in part via modulation of p53, Ca+2, and ROS signalling. Thus, the results suggest the potential cancer therapeutic use of tomatine in HCC patients.

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Section: Introductionmentioning

confidence: 99%

In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma

et al. 2022

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“…Tomatine has also been reported to exhibit various pharmacological activities. For example, tomatine inhibits the growth of human ovarian (Skov3) and breast (MCF-7) cancer cells [ 18 , 19 ]. It also shows immunostimulating effects as a vaccine adjuvant against infectious diseases and cancer immunotherapy [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

“…Tomatine is a solanum alkaloid similar to solanine, which is a well-known toxic glycoalkaloid in potatoes [ 16 ]; however, in vivo studies have demonstrated that oral tomatine administration is less toxic or non-toxic compared with other glycoalkaloids [ 17 ]. Tomatine has also been reported to exhibit several biological activities including anticancer [ 18 , 19 ], immunostimulatory [ 20 ], anti-inflammatory [ 21 ], and antibiotic [ 22 ] effects. Esculeoside A was isolated and identified as the major constituent in ripe red tomatoes by Fujiwara et al [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Content of Two Major Steroidal Glycoalkaloids in Tomato (Solanum lycopersicum cv. Micro-Tom) Mutant Lines at Different Ripening Stages

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et al. 2022

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Esculeoside A and tomatine are two major steroidal alkaloids in tomato fruit (Solanum lycopersicum) that exhibit anti-inflammatory, anticancer, and anti-hyperlipidemia activities. Tomatine contained in immature tomato fruit is converted to esculeoside A as the fruit matures. To develop new tomato varieties based on the content analysis of functional secondary metabolites, 184 mutant lines were generated from the original cultivar (S. lycopersicum cv. Micro-Tom) by radiation breeding. Ultra-performance liquid chromatography coupled with evaporative light scattering detector was used to identify the mutant lines with good traits by analyzing tomatine and esculeoside A content. Compared with the original cultivar, candidates for highly functional cultivars with high esculeoside A content were identified in the mature fruit of the mutant lines. The mutant lines with low and high tomatine content at an immature stage were selected as edible cultivars due to toxicity reduction and as a source of tomatine with various pharmacological activities, respectively. During the process of ripening from green to red tomatoes, the rate of conversion of tomatine to esculeoside A was high in the green tomatoes with a low tomatine content, whereas green tomatoes with a high tomatine content exhibited a low conversion rate. Using methanol extracts prepared from unripe and ripe fruits of the original cultivar and its mutant lines and two major compounds, we examined their cytotoxicity against FaDu human hypopharynx squamous carcinoma cells. Only tomatine exhibited cytotoxicity with an IC50 value of 5.589 μM, whereas the other samples did not exhibit cytotoxicity. Therefore, radiation breeding represents a useful tool for developing new cultivars with high quality, and metabolite analysis is applicable for the rapid and objective selection of potential mutant lines.

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“…TT suppresses proliferation and inhibits autophagy to induce apoptosis in Skov3 cells of ovarian cancer (OC), which was confirmed by measuring the expression of the Beclin-1 gene. Additionally, this GA inhibits the PI3K/Akt/mTOR pathway ( Wu et al, 2021 ). TT induces necroptosis and caspase-independent apoptosis in human colon cancer (CLC) cells, especially those with a hyperactivated PI3K/AKT pathway.…”

Section: Antitumor Effects Of Solanaceae Glycoalka...mentioning

confidence: 99%

Anticancer activity of glycoalkaloids from Solanum plants: A review

2022

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Cancer is still one of the main causes of death worldwide. For this reason, new compounds that have chemotherapeutic potential have been identified. One such group of substances is Solanaceae glycoalkaloids (GAs). They are natural compounds produced by plants widely used in traditional medicine for healing many disorders. Among others, GAs exhibit significant antitumor properties, for example, a strong inhibitory effect on cancer cell growth. This activity can result in the induction of tumor cell apoptosis, which can occur via different molecular pathways. The molecular mechanisms of the action of GAs are the subject of intensive research, as improved understanding could lead to the development of new cancer therapies. The genetic basis for the formation of neoplasms are mutations in protooncogenes, suppressors, and apoptosis-controlling and repair genes; therefore, substances with antineoplastic properties may affect the levels of their expression or the levels of their expression products. Therapeutic compounds can be applied separately or in combination with other drugs to increase the efficiency of cancer therapy; they can act on the cell through various mechanisms at different stages of carcinogenesis, inducing the process of apoptosis, blocking cell proliferation and migration, and inhibiting angiogenesis. This review summarizes the newest studies on the anticancer properties of solanine (SN), chaconine (CH), solasonine (SS), solamargine (SM), tomatine (TT) and their extracts from Solanum plants.

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α-Tomatine, a novel early-stage autophagy inhibitor, inhibits autophagy to enhance apoptosis via Beclin-1 in Skov3 cells

Cited by 20 publications

References 49 publications

In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma

In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma

Content of Two Major Steroidal Glycoalkaloids in Tomato (Solanum lycopersicum cv. Micro-Tom) Mutant Lines at Different Ripening Stages

Anticancer activity of glycoalkaloids from Solanum plants: A review

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