Antiproliferative activity of Solanum lycocarpum alkaloidic extract and their constituents, solamargine and solasonine, in tumor cell lines

Munari, Carla Carolina; Oliveira, Pollyanna Francielli de; Campos, Jacqueline Costa Lima; Martins, Sabrina de Paula Lima; Costa, Juliana C. Da; Bastos, Jairo Kenupp; Tavares, Denise Crispim

doi:10.1007/s11418-013-0757-0

Cited by 84 publications

(75 citation statements)

References 28 publications

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“…Solamargine, a plant derived steroidal glycoalkaloid, has been found to inhibit growth and induce apoptosis in several cancer types [16-20]. Solamargine reduced the growth of metastatic and primary melanoma cells via disrupting the intrinsic apoptosis pathway [20].…”

Section: Introductionmentioning

confidence: 99%

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

Tang

Zheng

et al. 2017

Cell Physiol Biochem

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Background/Aims: Solamargine, one natural photochemical component from traditional plants, has been shown to have anti-cancers properties. We previously showed that solamargine inhibited the growth of non-small-cell lung cancer (NSCLC) cells through suppression of prostaglandin E2 (PGE₂) receptor EP4 gene and regulation of downstream signaling pathways. However, the detailed mechanism underlying this, especially in combination of metformin, a known AMPK activator, still remained to be determined. Methods: Cell viability was measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and colorimetric 5-bromo-2-deoxyuridine (BrdU) ELISA methods, respectively. Western blot analysis and immunohistochemistry were performed to examine the phosphorylation and protein expressions of signal transducer and activator of transcription 3 (Stat3), SP1, forkhead box O3a (FOXO3a), and insulin-like growth factor (IGF)-IGF binding protein 1 (IGFBP1). The expression of IGFBP1 mRNA was measured by quantitative real time PCR (qRT-PCR). Silencing of FOXO3a and IGFBP1 were examined by siRNA procedures. Exogenously expression of SP1, FOXO3a, and IGFBP1 were carried out by transient transfection assays. The promoter activity of IGFBP1 was tested using Secrete-Pair^TM Dual Luminescence Assay Kit. A xenografted tumor model was used to further test the effect of solamargine in combining with metformin in vivo. Results: We further demonstrated that solamargine inhibited growth and induced cell cycle arrest in other NSCLC cell lines. Through mechanism-based approaches, we showed that solamargine decreased the phosphorylation of Stat3; In addition, solamargine induced FOXO3a, whereas reduced SP1 protein levels; all of which were abrogated in cells with overexpressed Stat3 gene. Interestingly, there is interaction between FOXO3a and SP1. Moreover, solamargine increased mRNA, protein expression and promoter activity of IGFBP1, which was not observed in cells with overexpressed SP1 or with silenced FOXO3a genes. Finally, ablation of IGFBP1 expression by siRNA blocked the effect of solamargine on cell growth inhibition. More importantly, there was a synergy of combination of solamargine and metformin. Similar findings were also observed in vivo. Conclusion: Our results show that solamargine increases IGFBP1 gene expression through inactivation of Stat3, followed by regulation and reciprocal interaction of FOXO3a and SP1 in vitro and in vivo. This ultimately leads to suppression of human lung cancer cell growth. Moreover, this is a synergy of solamargine in combination with metformin in this process. This study unravels a novel mechanism underlying the anti-lung cancer effects of solamargine in combination of metformin, and suggests a potential new lung cancer associated therapy.

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Section: Introductionmentioning

confidence: 99%

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

Tang

Zheng

et al. 2017

Cell Physiol Biochem

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“…Tais glicoalcaloides têm sido citados pelo seu efeito citotóxico contra linhagens de células tumorais. (Tiossi, 2010;Munari et al, 2014).…”

Section: Características Botânica Química E Farmacológicaunclassified

“…Também foram identificadas cinco saponinas esteroidais, liconosídeos Ia, Ib, II, III e IV e um pseudoalcalóide esteroidal oligoglicosídeo, denominado lobofrutosídeo (Nakamura et al, 2008).…”

Section: Características Botânica Química E Farmacológicaunclassified

Determinação dos parâmetros anatômicos, físico-químico e fitoquímicos das folhas de Solanum lycocarpum A. St.- Hill

Gallon

Barros

Silva

et al. 2015

Rev. bras. plantas med.

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RESUMO:A espécie vegetal Solanum lycocarpum, Solanaceae, popularmente conhecida como lobeira, está distribuída por todo o Brasil, principalmente em áreas do cerrado. Estudos comprovam que os frutos possuem diversas atividades e, atualmente, estão sendo utilizados no tratamento da diabetes. As folhas são utilizadas popularmente contra afecções das vias urinárias, cólicas abdominais e renais, espasmos e epilepsia, porém são poucos os estudos científicos que verificam as atividades farmacológicas das folhas. Assim, torna-se necessária a determinação de parâmetros anatômicos, físico-químicos e fitoquímicos que auxiliarão em futuras identificações e controle de qualidade da droga vegetal. Neste estudo foi realizada a coleta, secagem e pulverização das folhas de Solanum lycocarpum para a obtenção da droga vegetal e posterior caracterização desta. As análises microscópicas do pecíolo, nervura central e mesofilo revelaram características típicas da família Solanaceae, observando-se um sistema vascular bicolateral e a presença de areia cristalina e tricomas estrelados. A triagem fitoquímica, constatou a presença de taninos, flavonoides, esteróides e triterpenos, cumarinas e saponinas. Obteve-se o teor médio de 9,90% de perda por dessecação, 7,91% de cinzas totais e de 0,37% de cinzas insolúveis em ácidos. Para as substâncias extraíveis por álcool, o teor médio encontrado foi de 14,479% para o método de extração por Soxhlet e 0,987% para o método de extração a frio. Assim, espera-se que esses dados possam ser utilizados na identificação e controle de qualidade da droga vegetal de Solanum lycocarpum para a produção de novos medicamentos fitoterápicos.Palavras chave:Solanum lycocarpum, parâmetros analíticos, Solanaceae.ABSTRACT: Determination of the anatomics, physical-chemicals and phytochemicals parameters of the Solanum lycocarpum A.St.-Hill leaves. The plant species Solanum lycocarpum, Solanaceae, most known as lobeira, are distributed throughout Brazil, especially in Cerrado areas. Studies show that the fruits own different properties and, currently, are being used in the treatment of diabetes. Even though the leaves are being used by the general population against urinary tract disorders, renal and abdominal cramps, spasms and epilepsy, there are few scientific studies that verify the possible pharmacological activities of leaves. This shows that it is necessary to research and determinate the anatomic, physical-chemicals and the phytochemicals parameters that are going to help in the identification and quality assurance of the drug. In this study the leaves of Solanum lycocarpum were collected, dried and pulverized in order to be obtained the plant drug for further characterization.. Microscopic analyzes of the petiole, midrib and mesophyll showed typical features of the Solanaceae family, by detecting a biocolateral vascular system and the presence of crystallines and and stellatetrichomes. In the phytochemical screening performed, the tanning, flavonoids, sterols and triterpenes, coumarins and saponins were found. ...

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“…In order to better understand the cytotoxic activity of manool, a normal cell line (V79, Chinese hamster lung fibroblasts) was used to compare its selectivity. The choice of V79 cells for comparison is due the fact it is a well characterized cell line and commonly used in cytotoxicity studies (Bradley et al 1981;Munari et al 2014). …”

Section: Introductionmentioning

confidence: 99%

Manool, a Salvia officinalis diterpene, induces selective cytotoxicity in cancer cells

et al. 2015

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Manool, a diterpene isolated from Salvia officinalis, was evaluated by the XTT colorimetric assay for cytotoxicity and selectivity against different cancer cell lines: B16F10 (murine melanoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), HepG2 (human hepatocellular carcinoma), and MO59J, U343 and U251 (human glioblastoma). A normal cell line (V79, Chinese hamster lung fibroblasts) was used to compare the selectivity of the test substance. Manool exhibited higher cytotoxic activity against HeLa (IC 50 = 6.7 ± 1.1 lg/mL) and U343 (IC 50 = 6.7 ± 1.2 lg/mL) cells. In addition, in the used experimental protocols, the treatment with manool was significantly more cytotoxic for different tumor cell lines than for the normal cell line V79 (IC 50 = 49.3 ± 3.3 lg/mL), and showed high selectivity. These results suggest that manool may be used to treat cancer without affecting normal cells.

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Antiproliferative activity of Solanum lycocarpum alkaloidic extract and their constituents, solamargine and solasonine, in tumor cell lines

Cited by 84 publications

References 28 publications

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

Determinação dos parâmetros anatômicos, físico-químico e fitoquímicos das folhas de Solanum lycocarpum A. St.- Hill

Manool, a Salvia officinalis diterpene, induces selective cytotoxicity in cancer cells

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