Scutellariabarbata D. Don extraction selectively targets stemness-prone NSCLC cells by attenuating SOX2/SMO/GLI1 network loop

Chen, Weiwei; Gong, Kaikai; Yang, Lijuan; Dai, Jing; Zhang, Qian; Wang, Feng; Li, Xuelin; Xi, Sichuan; Du, Jing

doi:10.1016/j.jep.2020.113295

Cited by 11 publications

(13 citation statements)

References 44 publications

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“…SBD, one of the well-known Chinese herbs medicines, has been widely used clinically for treating malignant cancer for many years. As mentioned earlier, SBE induced cancer cell apoptosis by activating MAPK and ER stress signaling pathway, restrained tumor angiogenesis via inhibiting Hedgehog signaling pathway, and dinimished G2 arrest in lung cancer cells by regulating mutiple signaling pathways related with the cell cycle checkpoint enzymes [5,[11][12][13]. These studies have been indicated that SBD is a potential drug in anti-tumor..…”

Section: Introductionmentioning

confidence: 86%

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Scutellaria Barbata D.Don (SBD) Extracts Suppressed Tumor Growth, Metastasis and Angiogenesis in Prostate Cancer Via PI3K/Akt Pathway

Sheng

Zhao

Zhu

et al. 2021

Preprint

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Background: Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate that has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in cancer.Materials and methods: CCK8, Edu assays and colony formation assay were performed to assess the effect of SBD on PCa cell growth. Effect of SBD on apoptosis and cell cycle was detected by flow cytometry. Transwell and wounding healing assay were performed to detected the invasion and migration activities of PCa cells. Western blot was employed to detect the protein expression. 2RRV1 mouse xenograft model was established to detect the effect of SBD on prostate cancer. Angiogenesis was analysed by coculturing PCa cell lines and HUVECs.Results: The results showed that SBD induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. SBD induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signalling pathway. Treatment with SBE also significantly decreased the cell migration and invasion via phenotypic inversion of EMT that was characterized by the increased expression of E-cadherin and Vimentin, and decreased expression of N-cadherin, which could be partially attributed to inhibiting PI3K/AKT signalling pathway. Subsequently, using AKT inhibitor MK2206, we performed that PI3K/AKT are also involved in cell apoptosis and metastasis of PCa cells stimulated by SBE. In addition, to its direct effects on PCa cells, SBD also exhibited anti-angiogenic properties. SBD alone or conditioned media from SBD-treated PCa cells inhibited HUVEC tube formation on Matrigel without affecting HUVEC viability. Furthermore, 22RV1 xenograft C57BL/6 mice treated with SBE in vivo showed a significant decrease in tumour size and tumour weight without toxicity. In addition, administration with medium- or high-dose of SBE significantly inhibited the cell proliferation and promoted the damage of tumour tissues.Conclusions: Collectively, our in vitro and in vivo findings suggest that SBE had the potential to develop into a safe and potent alternative therapy for PCa patients.

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Section: Introductionmentioning

confidence: 86%

“…The epithelial-to-mesenchymal transition (EMT) is considered a hallmark of the aggressive invasion and metastasis of advanced tumours [2]. In previous studies, EMT can bring about the malignant transformation of PCa, and thus leading to its invasion and migration [5].…”

Section: Introductionmentioning

confidence: 99%

Scutellaria Barbata D.Don (SBD) Extracts Suppressed Tumor Growth, Metastasis and Angiogenesis in Prostate Cancer Via PI3K/Akt Pathway

Sheng

Zhao

Zhu

et al. 2021

Preprint

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“…Mechanistically, Curcumin downregulates the expression levels of CSCs markers, including CD133, CD44, ALDHA1, Nanog and Oct4, by inhibiting the HH and Wnt/b-catenin pathways (186). In addition, SBE suppresses stemness-like phenotypes in NSCLC by targeting the Sox2/Smo/Gli1 positive feedback loop (187).…”

Section: Natural Products Eliminate Lung Cancer Cscs By Inhibiting Th...mentioning

confidence: 99%

Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances

Ullah

et al. 2022

Front. Oncol.

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According to the latest statistics from the International Agency for Research on Cancer (IARC), lung cancer is one of the most lethal malignancies in the world, accounting for approximately 18% of all cancer-associated deaths. Yet, even with aggressive interventions for advanced lung cancer, the five-year survival rate remains low, at around 15%. The hedgehog signaling pathway is highly conserved during embryonic development and is involved in tissue homeostasis as well as organ development. However, studies have documented an increasing prevalence of aberrant activation of HH signaling in lung cancer patients, promoting malignant lung cancer progression with poor prognostic outcomes. Inhibitors targeting the HH pathway have been widely used in tumor therapy, however, they still cannot avoid the occurrence of drug resistance. Interestingly, natural products, either alone or in combination with chemotherapy, have greatly improved overall survival outcomes for lung cancer patients by acting on the HH signaling pathway because of its unique and excellent pharmacological properties. In this review, we elucidate on the underlying molecular mechanisms through which the HH pathway promotes malignant biological behaviors in lung cancer, as well as the potential of inhibitors or natural compounds in targeting HH signaling for clinical applications in lung cancer therapy.

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“…The epithelial-to-mesenchymal transition (EMT) is considered a hallmark of the aggressive invasion and metastasis of advanced tumours [ 2 ]. In previous studies, EMT can bring about the malignant transformation of PCa, thus leading to its invasion and migration [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…SBD has been known in traditional chinese medicine for over 400 years for its heating-releasing and detoxifying proprties, which means it can kill aberrant cells in the human body. Mounting evidence showed that SBD had an inhibitory effect on lung cancer, liver cancer, leukemia, and breast cancer [ 5 , 12 – 14 ]. At the same time, it has been reported that Hedyotis diffusa Willd (HD) had positive effect on the treatment of malignant tumor [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway

Sheng

Zhao

Zhu

et al. 2022

BMC Complement Med Ther

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Background Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate which has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in cancer. Materials and methods CCK8, Edu assays and colony formation assay were performed to assess the effect of SBD on PCa cell growth. Effect of SBD on apoptosis and cell cycle was detected by flow cytometry. Transwell and wounding healing assay were conducted to detect the invasion and migration activities of PCa cells. Western blot was employed to detect the protein expression. 2RRV1 mouse xenograft model was established to detect the effect of SBD on prostate cancer. Angiogenesis was analysed by coculturing PCa cell lines and HUVECs. Results The results showed that SBD induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. SBD induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signalling pathway. Treatment with SBD also significantly decreased the cell migration and invasion via phenotypic inversion of EMT that was characterized by the increased expression of E-cadherin and Vimentin, and decreased expression of N-cadherin, which could be partially attributed to inhibiting PI3K/AKT signalling pathway. Subsequently, using AKT inhibitor MK2206, we concluded that PI3K/AKT are also involved in cell apoptosis and metastasis of PCa cells stimulated by SBD. Apart from its direct effects on PCa cells, SBD also exhibited anti-angiogenic properties. SBD alone or conditioned media from SBD-treated PCa cells reduced HUVEC tube formation on Matrigel without affecting HUVEC viability. Furthermore, 22RV1 xenograft C57BL/6 mice treated with SBD in vivo showed a significant inhibitory in tumour size and tumour weight without toxicity. In addition, administration with medium- or high-dose of SBD significantly inhibited the cell proliferation and enhanced the damage to tumour tissues. Conclusions Collectively, our in vitro and in vivo findings suggest that SBD has the potential to develop into a safe and potent alternative therapy for PCa patients.

show abstract

Scutellariabarbata D. Don extraction selectively targets stemness-prone NSCLC cells by attenuating SOX2/SMO/GLI1 network loop

Cited by 11 publications

References 44 publications

Scutellaria Barbata D.Don (SBD) Extracts Suppressed Tumor Growth, Metastasis and Angiogenesis in Prostate Cancer Via PI3K/Akt Pathway

Scutellaria Barbata D.Don (SBD) Extracts Suppressed Tumor Growth, Metastasis and Angiogenesis in Prostate Cancer Via PI3K/Akt Pathway

Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances

Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway

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