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Metastatic Renal cell carcinoma (RCC) remains a difficult oncologic challenge. Salinomycin is a monocarboxylic polyether antibiotic, which has been proved to possess anti-tumor activities in multiple types of cancer cells. However, its effects on RCC cells remains unclear. In our study, salinomycin could inhibit the proliferation and viability of RCC cell lines 786-O and ACHN. The TUNEL assay revealed that treatment with salinomycin induced DNA breaking in RCC cells. Consistently, Western blotting showed up-regulation of pro-apoptotic biomarkers (cleaved caspase3/9 and cleaved PARP1) and down-regulation of anti-apoptotic biomarker (survivin) in RCC cells after salinomycin treatment, suggesting that salinomycin could induce RCC cell apoptosis. salinomycin treatment also suppressed the sphere formation ability of RCC cells and decreased the expressions of CD105, ALDH1 and CD44, biomarkers for reflecting the stemness of RCC cells. salinomycin treatment effectively down-regulated SMO and Gli1, two key proteins in Hedghog signaling pathway, in a dose-dependent manner. Moreover, salinomycin could suppress the invasion and migration of RCC cells in the presence of TGF-β1, as observed in wound-healing and Transwell assays. salinomycin treatment attenuated TGF-β1-induced epithelial-mesenchymal transition (EMT), as evidenced by its ability to increase E-cadherin expression and decrease N-cadherin, Snail and MMP-2 expressions in RCC cells. Finally, salinomycin inhibited the tumorigenecity of RCC cells in vivo. Our study provides the evidence that salinomycin possess multiple anti-tumor activities against RCC, as it, in particular, suppressed the cancer stem cell properties and attenuated TGF-β-induced EMT. Therefore, it may serve as a potentially therapeutic candidate for metastatic RCC and improve the prognosis of RCC patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Epithelial-to-mesenchymal transition (EMT) is the major cause of breast cancer to initiate invasion and metastasis. Salinomycin (Sal) has been found as an effective chemical compound to kill breast cancer stem cells. However, the effect of Sal on invasion and metastasis of breast cancer is unclear. In the present study, we showed that Sal reversed transforming growth factor-β1 (TGF-β1) induced invasion and metastasis accompanied with down-regulation of MMP-2 by experiments on human breast cancer cell line MCF-7. Sal was able to inhibit TGF-β1-induced EMT phenotypic transition and the activation of key signaling molecules involved in Smad (p-Smad2/3,Snail1) and non-Smad (β-catenin, p-p38 MAPK) signals which cooperatively regulate the induction of EMT. Importantly, in a series of breast cancer specimens, we found strong correlation among E-cadherin expression, β-catenin expression, and the lymph node metastatic potential of breast cancer. Our research suggests that Sal is promised to be a chemotherapeutic drug by suppressing the metastasis of breast cancer., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

6 USP37 knockdown inhibits stemness, cell invasion and EMT via Hedgehog signaling pathway in breast cancer. a, b MCF-7 cells were incubated with 0.5 M purmorphamine for 24 and 48 h. a Hedgehog pathway constituents were examined via western blotting. Reference 1 Qin T, Li B, Feng X. Abnormally elevated USP37 expression in breast cancer stem cells regulates stemness, epithelial-mesenchymal transition and cisplatin sensitivity. [Extracted from the article]

Renal cell carcinoma (RCC) is a common urinary malignancy that is resistant to chemotherapy and radiotherapy. Osthole, a monomer compound extracted from a traditional Chinese herb, has potent anti-tumor effects on various types of cancer cells. However, the therapeutic effects of osthole on RCC remain unclear. In our study, osthole could suppress the proliferation and colony formation of two RCC cell lines, ACHN and 786-O cells, in a dose-dependent manner. Treatment with osthole resulted in a significant, dose-dependent increase in the expression of pro-apoptotic proteins (cleaved caspase-3 and Bax) and decreased expression of anti-apoptotic proteins (Bcl-2 and survivin), which were consistent with evidence of apoptotic nuclear morphology revealed by DAPI staining. Pre-treatment with osthole attenuated the migratory and invasive abilities of RCC cells in a dose-dependent manner, as evidenced by a reduction in migrating cells in a Transwell assay and a decreased wound closure ratio in a scratch assay as compared with the control. Additionally, osthole down-regulated the expression of migration/invasion-related proteins matrix metalloproteinase (MMP)-2 and MMP-9. Osthole significantly up-regulated epithelial biomarkers (E-cadherin and beta-catenin) and down-regulated mesenchymal biomarkers (N-cadherin and vimentin). Furthermore, our results suggest that osthole suppressed the expression of epithelial–mesenchymal transition transcriptional factors Smad-3, Snail-1, and Twist-1. Taken together, the results of this study suggest that osthole might be a potential novel herbal agent against RCC. [ABSTRACT FROM AUTHOR]