Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway

Wu, Chin Han; Liang, Chia Hua; Shiu, Li Yen; Chang, Li; Lin, Tsai Shiuan; Lan, C.‐C. E.; Tsai, Jui Chen; Wong, Tak Wah; Wei, Kai; Lin, Tzu Kai; Chang, Nan Shan; Sheu, Hamm Ming

doi:10.1016/j.jdermsci.2011.04.003

Cited by 28 publications

(46 citation statements)

References 31 publications

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“…Mouse models, most notably those employing the SKH-1 hairless immunocompetent mouse, proved to be useful and allowed the identification of critical molecular and biologic changes that trigger skin tumour development [[14], [15]]. They are also commonly used to assess the preclinical efficacy of novel treatments on SCC however, rather than on AK lesions [[10]; [9], [8], [16]].…”

Section: Discussionmentioning

confidence: 99%

Actinic keratosis modelling in mice: A translational study

et al. 2017

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BackgroundActinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC.ObjectivesHere we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin.MethodsHuman and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope.ResultsAn histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®.ConclusionThese data demonstrate that this mouse model of UV-B-induced skin lesions is predictive for the identification of novel therapeutic treatments for both early and advanced stages of the disease.

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Section: Discussionmentioning

confidence: 99%

Actinic keratosis modelling in mice: A translational study

et al. 2017

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“…31 A once-daily application of a topical solamargine gel to the skin caused the disappearance of UVB-induced microinvasive SCCs in 27 of 30 hairless mice within 10 weeks. In addition, the gel cured 10 of 13 patients with actinic keratosis (AK) after 16 weeks.…”

Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 99%

Chemistry and Anticarcinogenic Mechanisms of Glycoalkaloids Produced by Eggplants, Potatoes, and Tomatoes

Friedman¹

2015

J. Agric. Food Chem.

168

106

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Inhibition of cancer can occur via apoptosis, a genetically directed process of cell self-destruction that involves numerous biomarkers and signaling pathways. Glycoalkaloids are nitrogen-containing secondary plant metabolites found in numerous Solanaceous plants including eggplants, potatoes, and tomatoes. Exposure of cancer cells to glycoalkaloids produced by eggplants (α-solamargine and α-solasonine), potatoes (α-chaconine and α-solanine), and tomatoes (α-tomatine) or their hydrolysis products (mono-, di-, and trisaccharide derivatives and the aglycones solasodine, solanidine, and tomatidine) inhibits the growth of the cells in culture (in vitro) as well as tumor growth in vivo. This overview comprehensively surveys and consolidates worldwide efforts to define the following aspects of these natural compounds: (a) their prevalence in the three foods; (b) their chemistry and structure-activity relationships; (c) the reported factors (biomarkers, signaling pathways) associated with apoptosis of bone, breast, cervical, colon, gastric, glioblastoma, leukemia, liver, lung, lymphoma, melanoma, pancreas, prostate, and squamous cell carcinoma cell lines in vitro and the in vivo inhibition of tumor formation and growth in fish and mice and in human skin cancers; and (d) future research needs. The described results may make it possible to better relate the structures of the active compounds to their health-promoting function, individually, in combination, and in food, and allow the consumer to select glycoalkaloid-containing food with the optimal content of nontoxic beneficial compounds. The described findings are expected to be a valuable record and resource for further investigation of the health benefits of food-related natural compounds.

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“…A smaller number of studies have focused on the effect of glycoalkaloids on cancer in vivo in animal models [63][64][65]. The extract of the Brazilian fruit Solanum lycocarpum contains α-solamargine and α-solasonine and was tested for both anti-carcinogenic and anti-genotoxic effected in rats [63].…”

Section: Of 26mentioning

confidence: 99%

“…An anti-genotoxic effect was also observed for rats receiving the extract using the micronucleus and comet assay on bone marrow or liver cells harvested 24 h after administering methyl methanesulfonate on the 14th day. The extract of Solanum incanum contains α-solamargine as its main active ingredient and a 65:35 ratio of α-solamargine to α-solasonine as determined by reverse-phase HPLC [64]. Hairless female mice were subjected to a protocol of irradiation with UV-B (312 nm) to induce papillomas and microinvasive squamous cell carcinomas (MISCC).…”

Section: Of 26mentioning

confidence: 99%

Glycoalkaloids: Structure, Properties, and Interactions with Model Membrane Systems

Nepal

Stine

2019

Processes

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The glycoalkaloids which are secondary metabolites from plants have proven to be of significant interest for their biological properties both in terms of their roles in plant biology and the effects they exhibit when ingested by humans. The main feature of the action of glycoalkaloids is their strong binding to 3β-hydroxysterols, such as cholesterol, to form complexes with the consequence that membrane structure is significantly perturbed, and leakage or release of contents inside cells or liposomes becomes possible. The glycoalkaloids have been studied for their ability to inhibit the growth of cancer cells and in other roles such as vaccine adjuvants and as synergistic agents when combined with other therapeutics. The glycoalkaloids have rich and complex physical behavior when interacting with model membranes for which many aspects are yet to be understood. This review introduces the general properties of glycoalkaloids and aspects of their behavior, and then summarizes their effects against model membrane systems. While there are many glycoalkaloids that have been identified, most physical or biological studies have focused on the readily available ones from tomatoes (α-tomatine), potatoes (α-chaconine and α-solanine), and eggplant (α-solamargine and α-solasonine).Plants of the Solanaceae family include tomatoes, potatoes, and eggplants, and are well known to produce secondary metabolites known as glycoalkaloids [21]. The glycoalkaloids are produced in the leaves, flowers, and roots of the plant. In the case of potatoes, they are also found in the sprouts [22]. Tomato plants produce the glycoalkaloid α-tomatine, potato plants produce both α-chaconine and α-solanine, and eggplants produce both α-solamargine and α-solasonine (see Figure 1). Green tomatoes can have up to 500 mg kg −1 of tomatine in the fruit, which will decrease to near 5 mg kg −1 upon ripening [5]. The concentration of tomatine in the vines will stay near 500 mg kg −1 . The amount of α-tomatine in red tomatoes consumed by humans is 10-30 mg kg −1 , but if green tomatoes are consumed then the level will be 200-500 mg kg −1 . In eggplants, the average glycoalkaloid concentration for 21 varieties was found to vary from 0.625-20.5 mg kg −1 [23]. The glycoalkaloid content of potatoes varies widely with potato type and conditions of cultivation [24] and will increase in damaged plants [25]. The glycoalkaloid content of normal potato tubers is reported as 12-20 mg kg −1 while green tubers can have 250-280 mg kg −1 and green skin 1500-2200 mg kg −1 [26]. The enzymes involved in the natural synthesis of the oligosaccharides of the glycoalkaloids have been reviewed [27]. Structure of GlycoalkaloidsThe glycoalkaloids consist of a nitrogen-containing steroidal aglycone and an attached oligosaccharide. The prefix αrefers to the compound with fully intact oligosaccharide, whereas removal of one sugar would be denoted by a β-prefix, removal of two sugars by a γ-prefix, and removal of three for a tetrasaccharide by a δ-prefix. The aglycones are referred to as t...

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Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway

Cited by 28 publications

References 31 publications

Actinic keratosis modelling in mice: A translational study

Actinic keratosis modelling in mice: A translational study

Chemistry and Anticarcinogenic Mechanisms of Glycoalkaloids Produced by Eggplants, Potatoes, and Tomatoes

Glycoalkaloids: Structure, Properties, and Interactions with Model Membrane Systems

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