Solamargine triggers hepatoma cell death through apoptosis

Xie, Xiaodong; Zhu, Haitao; Yang, Hong Yul; Huang, Wenxi; Wu, Yingying; Wang, Ying; Luo, Yan‐Ling; Wang, Dongqing; Shao, Gang

doi:10.3892/ol.2015.3194

Cited by 31 publications

(35 citation statements)

References 37 publications

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“…Steroidal glycoalkaloids are naturally occurring nitrogen containing secondary metabolites found in plants of the Solanaceae family. Solamargine, a steroidal alkaloid glycoside extracted from the traditional Chinese herb Solanum incanum , has been reported to have various pharmacological functions including anti-cancer activities [22, 50, 51]. Although there were important discoveries revealed by other studies indicated multiple signaling pathways and molecular genes or proteins that involved in the anti-tumor responses of solamargine, the in-depth molecular mechanisms by which this agent in inhibition of tumor growth still remained to be elucidated.…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Furthermore, as the doses of SM increased, the suppression effect was enhanced. In the wound-healing assay, it was hypothesized that the width of the gap would decrease in a time-dependent manner, whereas after 24 h of treatment with 10 and 20 µM concentrations of SM, the width of the gap was increased compared with the size of the gap following 12 h. It was considered that this phenomenon was associated with the SM function in triggering HepG2 cells death by apoptosis (21). Use of a Matrigel-coated Transwell assay is a classical method to detect cell invasion, whereby the invasive HepG2 cells would digest the gel and penetrate the upper chamber to the lower wells.…”

Section: Discussionmentioning

confidence: 99%

“…Certain previous studies have reported that they Chinese herbs served important roles in regulating tumor cell behavior, including proliferation, apoptosis and metastasis (25)(26)(27). SM, extracted from Solanum incanum, is a traditional Chinese herb that was demonstrated to possess an effective function in inducing apoptosis of HepG2 and SMMC7721 cells in our previous study (21). In the present study, as conclusive results were not previously observed when investigating metastasis in SMMC7721 cells, the effects of SM on the migration and invasion on HepG2 cells were evaluated, and the concentration and treated durations were used as referenced in our previous study (21).…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study demonstrated that SM strongly inhibited growth and induced apoptosis of HCC cells, and we further investigated mechanisms underlying apoptosis induced by SM (21). Given this effect on the proliferation and apoptosis of HCC cells, the present study aimed to observe and determine whether SM contributes to an effective action on metastasis in hepatoblastoma cells and explore the possible underlying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Solamargine inhibits the migration and invasion of HepG2 cells by blocking epithelial-to-mesenchymal transition

et al. 2017

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Abstract. Solamargine (SM), a steroidal alkaloid glycoside purified from the Chinese traditional herb Solanum incanum, is known to possess various biological activities. However, only a few previous studies have reported the anti-metastatic activity of SM. In the present study, the inhibitory effects of SM on metastatic action were investigated in human HepG2 cells. The proliferation effects of SM on the HepG2 cells was evaluated by MTT and colony formation assays. Wound-healing and Transwell assays were performed to examine the migration and invasion effects on SM-treated HepG2 cells. The epithelial-to-mesenchymal transition (EMT)-associated markers (E-cadherin, Vimentin and N-cadherin) were detected by western blotting analysis. In the present study, MTT and colony formation assays indicated that SM suppressed HepG2 cell viability in a dose-dependent manner. The wound-healing and Transwell assays revealed that the migration and invasion activities were significantly inhibited following exposure to SM. EMT has been demonstrated to be essential for promoting migration and invasion in tumor cells and has often been characterized with a loss of epithelial markers (E-cadherin) and an increase of mesenchymal markers (Vimentin and N-cadherin). In the western blotting analysis, the expression level of E-cadherin was significantly upregulated compared with that in the control group, whereas the expression levels of N-cadherin and Vimentin were downregulated. Thus, it was suggested that the underlying mechanism of SM inhibits migration and invasion in HepG2 cells and is associated with suppression of EMT.

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“…Metastatic tumor cells possess several distinctive characteristics; they undergo epithelial-mesenchymal transition (EMT) and become invasive, become resistant to apoptosis and anoikis, and acquire the ability to disseminate and colonize secondary sites. SM inhibits the migration and invasion viability of HepG2 cells by blocking EMT [33] [34] [38].…”

Section: Metastasismentioning

confidence: 99%

Solasodine, Solamargine and Mixtures of Solasodine Rhamnosides: Pathway to Expansive Clinical Anticancer Therapies

Cham¹

2017

IJCM

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Cancer remains a major cause of mortality worldwide. Progresses have been made in the understanding of the molecular basis of cancer, cancer detection, and cancer treatment. Important strides by treating early-stage cancers have resulted in improved outcomes. Despite these achievements, mortality of cancer patients is high and still there is no cure. Some oncologists remain optimistic that cytotoxic chemotherapy will significantly improve cancer survival. However, notwithstanding the use of new and expensive single and more recently, combination drugs, the improvement of the response rates remains very low. In the United States, cancer death rates decreased by a mere 1.4% to 1.8% from 2004 to 2013. Compared to other serious diseases, the improvement of the cancer patient has been disappointingly lagging, and by far, most patients with advanced cancer eventually die of their disease. The need for improved cancer therapies is self-evident. This communication gives an overview of the overwhelming resurgence of solasodine and its glycosides in cancer therapy.

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Solamargine triggers hepatoma cell death through apoptosis

Cited by 31 publications

References 37 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

Solamargine inhibits the migration and invasion of HepG2 cells by blocking epithelial-to-mesenchymal transition

Solasodine, Solamargine and Mixtures of Solasodine Rhamnosides: Pathway to Expansive Clinical Anticancer Therapies

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