Saikosaponin D from Radix Bupleuri suppresses triple-negative breast cancer cell growth by targeting β-catenin signaling

Wang, Jixia; Qi, Huan; Zhang, Xiuli; Si, Wei; Xu, Fangfang; Hou, Tao; Zhou, Han; Wang, Anhui; Li, Guohui; Liu, Yanfang; Ye, Fang; Piao, Hulin

doi:10.1016/j.biopha.2018.09.038

Cited by 50 publications

(29 citation statements)

References 34 publications

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“…For example, SSd suppressed liver cancer proliferation by inhibiting cyclooxygenase 2 expression (27), as well as inhibiting the proliferation, invasion and migration of osteosarcoma cells (28). Previous studies also reported that SSd inhibited the proliferative activity of breast cancer cells, such as Hcc1937 and McF-7 (29,30). The results of the present study revealed that SSd induced apoptosis and inhibited the proliferative activity of Mda-MB-231 breast cancer cells.…”

Section: Discussionsupporting

confidence: 76%

Saikosaponin D inhibits autophagosome‑lysosome fusion and induces autophagy‑independent apoptosis in MDA‑MB‑231 breast cancer cells

Zhang

et al. 2020

Mol Med Rep

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The present study aimed to explore the effect of Saikosaponin d (SSd) and its underlying mechanism on apoptosis and autophagy in human breast cancer Mda-MB-231 cells. MTT assay, flow cytometry, western blotting and confocal fluorescence microscopy detection were employed. SSd, a kind of triterpenoid saponins extracted from Radix bupleuri, has been demonstrated to have the effects of anti-inflammatory, antioxidative and anticancer effects and can regulate autophagy. The present study revealed that SSd induced apoptosis through the activation of the p38 mitogen-activated protein kinase (MaPK) signaling pathway in human breast cancer Mda-MB-231 cells. The administration of SSd promoted the phosphorylation/activation of p38 MaPK in Mda-MB-231 cells, whereas pretreatment with SB203580, an effective p38 MaPK inhibitor, attenuated SSd-mediated apoptosis, the cleavage of ParP and the activation of caspase-3. in addition, SSd blocked autophagic degradation by inhibiting autolysosome formation, resulting in the accumulation of autophagosomes. Mechanistically, the results of the present study revealed that SSd inhibited the formation of autophagosomes by inhibiting autophagosome-lysosome fusion, rather than by damaging lysosome function. Furthermore, blocking autophagy degradation was not associated with SSd-mediated apoptosis. The genetic knockdown of autophagy-related protein 5 markedly reduced SSd-mediated lc3B-ii accumulation; however, it did not affect the SSd-mediated phosphorylation/activation of p38, cleavage of ParP, activation of caspase-3 or apoptosis. In conclusion, the findings of the present study suggest that SSd may induce apoptosis and block autophagic degradation, which provides further evidence of the association between the inhibition of autophagic degradation and cell death.

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Section: Discussionsupporting

confidence: 76%

Saikosaponin D inhibits autophagosome‑lysosome fusion and induces autophagy‑independent apoptosis in MDA‑MB‑231 breast cancer cells

Zhang

et al. 2020

Mol Med Rep

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“…21 Treatment with SSD also causes growth suppression and apoptosis-dependent death in triple-negative breast cancer cells. 22 SSDenhances the sensitivity of gefitinib in human non–small cell lung cancer cells via regulating the STAT3–BCL2 signaling pathway. 23 Furthermore, SSD has been reported to enhance cell radiosensitivity of liver cancer cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Saikosaponin D Inhibits Proliferation and Promotes Apoptosis Through Activation of MKK4–JNK Signaling Pathway in Pancreatic Cancer Cells</p>

Lai

Chen

et al. 2020

OTT

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Introduction: Pancreatic cancer remains one of the most lethal malignancies and has few treatment options. Saikosaponin D (SSD), a major bioactive triterpene saponin isolated from Bupleurum chinense, has been reported to exert cytotoxicity properties toward many cancer cells. However, the effects of SSD on pancreatic cancer have been little scrutinized. Methods: Here, we investigated the effect of SSD on the proliferation and apoptosis of human pancreatic cancer BxPC3 and PANC1 cells and the mouse pancreatic cancer cell line Pan02. Cell viability was determined by MTT assays and cell apoptosis analyzed by DAPI staining and flow cytometry. Expression levels of apoptosis-regulating markers and activity of the MKK4-JNK signaling pathway were determined by Western blotting. The inhibitor SP600125 was applied to confirm the role of the JNK pathway in SSD efficiency. Results: SSD significantly inhibited the proliferation of BxPC3, PANC1, and Pan02 cells in a concentration-and time-dependent manner. Flow-cytometry analysis indicated obvious apoptosis induction after SSD exposure. Furthermore, SSD significantly triggered cleavage of caspase 3 and caspase 9 proteins and increased the expression of FoxO3a. In addition, activity of the MKK4-JNK pathway was dramatically increased after treatment with SSD in BxPC3 cells. SSD obviously stimulated phosphorylation of JNK, cJun, and SEK1/MKK4 proteins within 30 minutes. The addition of SP600125 blocked the activation of SSD on the MKK4-JNK regulatory pathway and reversed the effects of SSD on proliferation inhibition and apoptosis induction in BxPC3 cells. Conclusion: These results revealed that SSD was capable of suppressing tumor growth and promoting apoptosis of pancreatic cancer cells via targeting the MKK4-JNK signaling pathway, indicating the possibility of further developing SSD as a potential therapeutic candidate for pancreatic cancer.

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“…Among them, Resveratrol inhibits the invasion and metastasis of colon cancer through reversal of EMT via the AKT/GSK-3β/Snail signaling cascade (Yuan et al, 2019). Moreover, Wogonin (Tian et al, 2014), Ursolic acid (Yan et al, 2010), Zerumbone (Samad et al, 2018), 6-Gingerol (Weng et al, 2010), Coumarin (Zhang E. et al, 2018), Resveratrol (Gao et al, 2020), Rutin (Thomas et al, 2017), Oleanolic acid (Wang et al, 2018) were involved in regulating the proliferation, apoptosis, invasion, as well as metastasis of HCC. Oleanolic acid serves an anti-EMT effect in HCC by increasing iNOS dimerization, NO production, and NT of EMT-related proteins (Wang H. et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…According to TCM, BJJP can promote circulation, relieve stasis, improve immunity, eliminate pathogenic factors, as well as disperse and soften hard masses; therefore, it is suitable for patients with liver fibrosis and cirrhosis (Yao et al, 2004;Li M. et al, 2018). Some of the ingredients, such as rhubarb (Wu et al, 2017) and radix bupleuri (Wang et al, 2018), have been shown to inhibit tumor proliferation and metastasis via interruption of cellular signaling pathways, such as PI3K/Akt, MAPK/ERK, and Wnt/β-catenin. Importantly, BJJP has been shown to exert positive effects for the clinical treatment of HCC.…”

Section: Introductionmentioning

confidence: 99%

Biejiajian Pill Inhibits Carcinogenesis and Metastasis via the Akt/GSK-3β/Snail Signaling Pathway in Hepatocellular Carcinoma

Sun

Chen

Wen³

et al. 2021

Front. Pharmacol.

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Hepatocellular carcinoma (HCC) is among the most usual cancers globally. In China, Biejiajian pill (BJJP), Traditional Chinese Medicine clinical prescription, is broadly utilized for the prevention and therapy of HCC. However, the mechanisms by which BJJP exerts its effects on the prevention of tumor invasion and metastasis are still largely unknown. In this study, in vitro multiple hepatic cancer cell lines and an in vivo xenograft mice model were used to validate the preventive effects and molecular mechanisms of BJJP in HCC. We established that BJJP significantly repressed the proliferation, metastasis and infiltration of HCC cells. Furthermore, BJJP remarkably suppressed HCC cell migration, as well as invasion via epithelial-mesenchymal transition (EMT) by modulating Snail expression, which was associated with the repression of Akt/GSK-3β/Snail signaling axis activation. In vivo HCC xenograft results indicated that BJJP delayed HCC development and efficiently inhibited lung metastasis. Taken together, BJJP was shown to be an effective therapeutic agent against HCC through repression of the Akt/GSK-3β/Snail signaling cascade and EMT.

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Saikosaponin D from Radix Bupleuri suppresses triple-negative breast cancer cell growth by targeting β-catenin signaling

Cited by 50 publications

References 34 publications

Saikosaponin D inhibits autophagosome‑lysosome fusion and induces autophagy‑independent apoptosis in MDA‑MB‑231 breast cancer cells

Saikosaponin D inhibits autophagosome‑lysosome fusion and induces autophagy‑independent apoptosis in MDA‑MB‑231 breast cancer cells

<p>Saikosaponin D Inhibits Proliferation and Promotes Apoptosis Through Activation of MKK4–JNK Signaling Pathway in Pancreatic Cancer Cells</p>

Biejiajian Pill Inhibits Carcinogenesis and Metastasis via the Akt/GSK-3β/Snail Signaling Pathway in Hepatocellular Carcinoma

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