Schisandrin A inhibits triple negative breast cancer cells by regulating Wnt/ER stress signaling pathway

Xu, Xiaohong; Rajamanicham, Vinothakumar; Xu, Sujing; Liu, Zhoudi; Yan, Tao; Liang, Guang; Guo, Gui-Long; Zhou, Huiping; Wang, Yi

doi:10.1016/j.biopha.2019.108922

Cited by 44 publications

(36 citation statements)

References 29 publications

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“…Recently, Xu et al also found similar experiment results and investigated the possibility that Schisandrin A could suppress the cell cycle and introduce apoptosis of cells in TNBC though the Wnt/ER stress signaling pathway. However, they merely researched the activation of the Wnt/β-catenin and ER stress-related protein expression [23]. Collectively, our study confirmed the specific progress of the pathway in that cell apoptosis was induced by ER stress through suppressing the Wnt signaling pathway by combination delivery with tunicamycin and LiCl (Figure 4).…”

Section: Discussionsupporting

confidence: 69%

Tunicamycin-Induced Endoplasmic Reticulum Stress Promotes Breast Cancer Cell MDA-MB-231 Apoptosis through Inhibiting Wnt/β-Catenin Signaling Pathway

You

Yan

2021

Journal of Healthcare Engineering

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Triple negative breast cancer (TNBC) has significantly threatened human health. Many aspects of TNBC are closely related to Wnt/β-catenin pathway, and cell apoptosis induced by endoplasmic reticulum stress (ER stress) in TNBC may act as a potential target of non-chemotherapy treatment. However, how ER stress interacts with this pathway in TNBC has not yet been understood. Here, the tunicamycin and LiCl have been applied to MDA-MB-231. The related proteins’ expression was measured by western blotting. Moreover, acridine orange/ethidium bromide (AO/EB) staining was applied to test the apoptosis degree of the cells, and cell viability was tested by MTT experiment. Then, we found the ER stress and apoptosis degree of MDA-MB-231 were induced after treatment with tunicamycin. Besides, tunicamycin dose dependently inhibited both Wnt/β-catenin pathway and cells viability. Licl, an activator of Wnt/β-catenin signaling pathway, could significantly inhibit cell apoptosis. In conclusion, our study found that the activation of ER stress could promote the MDA-MB-231 apoptosis by repressing Wnt/β-catenin pathway, which provides some promising prospects and basic mechanism to the further research.

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Section: Discussionsupporting

confidence: 69%

Tunicamycin-Induced Endoplasmic Reticulum Stress Promotes Breast Cancer Cell MDA-MB-231 Apoptosis through Inhibiting Wnt/β-Catenin Signaling Pathway

You

Yan

2021

Journal of Healthcare Engineering

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“…[21] The bioactive phytochemical schisandrin A activated endoplasmic reticulum (ER) stress in TNBC cells, thus inducing apoptosis and cell cycle arrest. [22] Fisetin and quercetin disrupted activities of MAPK, STAT, PI3K/Akt pathways, and so on, for inhibiting cellular migration and reducing 3D invasion in TNBC cells. [23] Another phytochemical wikstromol from Wikstroemia indica suppressed the cell migration by decreasing NF-KB transcription and reducing activity/secretion of MMP-9, thereby inducing apoptosis in MDA-MB-231 cells.…”

Section: Discussionmentioning

confidence: 99%

Epoxyazadiradione induced apoptosis/anoikis in triple‐negative breast cancer cells, MDA‐MB‐231, by modulating diverse cellular effects

Lakshmi

Jalaja

Sasidhar

et al. 2021

J Biochem & Molecular Tox

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Triple-negative breast cancer (TNBC) is one of the most aggressive forms of its kind, which accounts for 15-20% of all breast cancers. As this cancer form lacks hormone receptors, targeted chemotherapy remains the best treatment option. Apoptosis and anoikis (detachment-induced cell death) induction by small molecules can prevent TNBC metastasis to a greater extent. Epoxyazadiradione (EAD) is a limonoid from the neem plant with an anticancer property. Here, we demonstrate that EAD induced mitochondria-mediated apoptosis and anoikis in TNBC cells (MDA-MB-231). Apart from this, it promotes antimigration, inhibition of colony formation, downregulation of MMP-9 and fibronectin, induction of G2/M phase arrest with downregulation of cyclin A2/cdk2, interference in cellular metabolism, and inhibition of nuclear factor kappa-B (NF-KB) nuclear translocation. Moreover, a significant reduction is observed in the expression of EGFR on the plasma membrane and nucleus upon treatment with EAD. Among the diverse cellular effects, anoikis induction, metabolic interference, and downregulation of membrane/nuclear EGFR expression by EAD are reported here for the first time. To summarize, EAD targets multiple cellular events to induce growth arrest in TNBC, and hence can be developed into the best antineoplastic agent in the future.

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“…The antitumor effects of Sch A were well-studied in several recent investigations. As a major member of dibenzocyclooctadiene lignans, Sch A not only impaired the proliferation, migration, and invasion of breast cancer, ovarian cancer, and thyroid cancer through prompting ER stress, inactivating Akt signals, and down-regulating miR-429, but also acted as a favorable chemosensitization agent in breast cancer and colon carcinoma [18,19,39,40]. Moreover, Xian et al [41] surprisingly found that Sch A could even improve the gefitinib resistance in non-small cell lung cancer cells (NSCLC) via inhibition of IKKβ/NF-κB signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Sch A, also commonly called as deoxyschizandrin, has long been used in traditional Chinese medicine to treat a variety of diseases such as spontaneous sweating and chronic asthma. The latest research on Sch A reveals that Sch A has a good growth inhibitory effect on human breast and ovarian cancer cells, and that its antitumor molecular mechanism may be related to ER stress, Wnt/β-catenin and PI3K/Akt signaling pathways [18,19]. Moreover, researchers have discovered that Sch A even exhibits great potential in reversing multidrug resistance (MDR) of breast cancer and colon cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Schizandrin A exhibits potent anticancer activity in colorectal cancer cells by inhibiting heat shock factor 1

Chen

Zheng

et al. 2020

Bioscience Reports

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Heat shock factor 1 (HSF1) is a powerful multifaceted oncogenic modifier that plays a role in maintaining the protein balance of cancer cells under various stresses. In recent studies, there have been reports of increased expression of HSF1 in colorectal cancer (CRC) cells, and the depletion of the HSF1 gene knockdown has inhibited colon cancer growth both in vivo and in vitro. Therefore, HSF1 is a promising target for colon cancer treatment and chemoprevention. In the present study, we found that Schizandrin A (Sch A) significantly inhibited the growth of CRC cell lines by inducing cell cycle arrest, apoptosis and death. Through HSE luciferase reporter assay and quantitative PCR (qPCR), we identified Sch A as a novel HSF1 inhibitor. In addition, Sch A could effectively inhibit the induction of HSF1 target proteins such as heat-shock protein (HSP) 70 (HSP70) and HSP27, whether in heat shock or normal temperature culture. In the Surface Plasmon Resonance (SPR) experiment, Sch A showed moderate affinity with HSF1, further confirming that Sch A might be a direct HSF1 inhibitor. The molecular docking and molecular dynamic simulation results of HSF1/Sch A suggested that Sch A formed key hydrogen bond and hydrophobic interactions with HSF1, which may contribute to its potent HSF1 inhibition. These findings provide clues for the design of novel HSF1 inhibitors and drug candidates for colon cancer treatment.

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Schisandrin A inhibits triple negative breast cancer cells by regulating Wnt/ER stress signaling pathway

Cited by 44 publications

References 29 publications

Tunicamycin-Induced Endoplasmic Reticulum Stress Promotes Breast Cancer Cell MDA-MB-231 Apoptosis through Inhibiting Wnt/β-Catenin Signaling Pathway

Tunicamycin-Induced Endoplasmic Reticulum Stress Promotes Breast Cancer Cell MDA-MB-231 Apoptosis through Inhibiting Wnt/β-Catenin Signaling Pathway

Epoxyazadiradione induced apoptosis/anoikis in triple‐negative breast cancer cells, MDA‐MB‐231, by modulating diverse cellular effects

Schizandrin A exhibits potent anticancer activity in colorectal cancer cells by inhibiting heat shock factor 1

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