Gomisin M2 from Baizuan suppresses breast cancer stem cell proliferation in a zebrafish xenograft model

Yang, Yeguo; Hao, Erhong; Pan, Xinliang; Tan, Darren Qiancheng; Du, Zhenhong; Xie, Jinling; Hou, Xin; Deng, Jiagang

doi:10.18632/aging.102323

Cited by 27 publications

(11 citation statements)

References 38 publications

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“…Moreover, S. chinensis has been certified as a safe nutritional ingredient by the European Food Safety Agency, and its fruit has been reported to have diverse pharmacological properties, including antioxidant, anti-inflammatory and antiallergic effects (17,40). GM2 extracted from S. chinensis has also been documented to exert various pharmacological effects, including preventing liver damage and reducing cancer cell proliferation (18,19,41). Based on these benefits, the present study explored the inhibitory effects of GM2 on IMQ-induced psoriasis-like skin inflammation and on TNF-α-and IFN-γ-stimulated keratinocytes after the purity of the GM2 isolated from S. chinensis was determined.…”

Section: Discussionmentioning

confidence: 99%

Gomisin M2 alleviates psoriasis‑like skin inflammation by inhibiting inflammatory signaling pathways

et al. 2021

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Psoriasis, a chronic inflammatory skin disease, is characterized by the excessive proliferation and impaired differentiation of epidermal keratinocytes and is accompanied by the increased infiltration of inflammatory cells. The condition requires long-term treatment and has no definitive cure. Hence, supplements and therapeutic agents have been intensely investigated. Gomisin M2 (GM2), a lignan extracted from Schisandra chinensis (Turcz). Baill. (Schisandraceae; S. chinensis), has demonstrated diverse pharmacological properties, including anticancer, anti-inflammatory and antiallergic effects. Based on these findings, the present study examined the effects of GM2 on an imiquimod (IMQ)-induced psoriasis mouse model and on keratinocytes stimulated by tumor necrosis factor (TNF)-α and interferon-γ. IMQ was topically applied to the back skin of mice for 7 consecutive days, and the mice were orally administered CD. These results showed that the oral administration of GM2 suppressed the symptoms of psoriasis, as evidenced by reductions in skin thickness, psoriasis area severity index scores for psoriasis lesions, transepidermal water loss and myeloperoxidase (MPO)-associated cell infiltration. Furthermore, GM2 reduced the pathologically increased levels of immunoglobulin G2a, MPO and TNF-α in the serum and T helper (Th)1 and Th17 cell populations in the spleen. GM2 decreased the gene expression of inflammatory-related cytokines and chemokines and inhibited the expression of signal transducer and activator of transcription 1 and nuclear factor-κB in the activated keratinocytes. These results suggested that GM2 from S. chinensis is a potential therapeutic candidate to alleviate psoriasis-like skin inflammation.

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Section: Discussionmentioning

confidence: 99%

Gomisin M2 alleviates psoriasis‑like skin inflammation by inhibiting inflammatory signaling pathways

et al. 2021

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“…A highly potent small-molecule inhibitor CWP232228 can preferentially inhibit bCSC proliferation via antagonizing the binding of β-catenin to T-cell factor (TCF) in the nucleus ( 246 ). Another natural product, gomisin M2, downregulates Wnt/β-catenin signaling and inhibits bCSC proliferation, mammosphere formation, and self-renewal ( 247 ). Studies indicate multiple interaction points or crosstalk between Notch and Wnt/β-catenin signaling pathways, and thus it is essential to focus on Notch-Wnt synergies in BC progression ( 248 ).…”

Section: Mechanisms and Approaches To Overcome Multimodal Drug Resist...mentioning

confidence: 99%

Breast Cancer Stem-Like Cells in Drug Resistance: A Review of Mechanisms and Novel Therapeutic Strategies to Overcome Drug Resistance

Saha

Lukong

2022

Front. Oncol.

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Breast cancer is the most frequent type of malignancy in women worldwide, and drug resistance to the available systemic therapies remains a major challenge. At the molecular level, breast cancer is heterogeneous, where the cancer-initiating stem-like cells (bCSCs) comprise a small yet distinct population of cells within the tumor microenvironment (TME) that can differentiate into cells of multiple lineages, displaying varying degrees of cellular differentiation, enhanced metastatic potential, invasiveness, and resistance to radio- and chemotherapy. Based on the expression of estrogen and progesterone hormone receptors, expression of human epidermal growth factor receptor 2 (HER2), and/or BRCA mutations, the breast cancer molecular subtypes are identified as TNBC, HER2 enriched, luminal A, and luminal B. Management of breast cancer primarily involves resection of the tumor, followed by radiotherapy, and systemic therapies including endocrine therapies for hormone-responsive breast cancers; HER2-targeted therapy for HER2-enriched breast cancers; chemotherapy and poly (ADP-ribose) polymerase inhibitors for TNBC, and the recent development of immunotherapy. However, the complex crosstalk between the malignant cells and stromal cells in the breast TME, rewiring of the many different signaling networks, and bCSC-mediated processes, all contribute to overall drug resistance in breast cancer. However, strategically targeting bCSCs to reverse chemoresistance and increase drug sensitivity is an underexplored stream in breast cancer research. The recent identification of dysregulated miRNAs/ncRNAs/mRNAs signatures in bCSCs and their crosstalk with many cellular signaling pathways has uncovered promising molecular leads to be used as potential therapeutic targets in drug-resistant situations. Moreover, therapies that can induce alternate forms of regulated cell death including ferroptosis, pyroptosis, and immunotherapy; drugs targeting bCSC metabolism; and nanoparticle therapy are the upcoming approaches to target the bCSCs overcome drug resistance. Thus, individualizing treatment strategies will eliminate the minimal residual disease, resulting in better pathological and complete response in drug-resistant scenarios. This review summarizes basic understanding of breast cancer subtypes, concept of bCSCs, molecular basis of drug resistance, dysregulated miRNAs/ncRNAs patterns in bCSCs, and future perspective of developing anticancer therapeutics to address breast cancer drug resistance.

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“…A previous study has shown that Wnt/β-catenin signaling pathway was deemed as a key mechanism of Sam68- mediated self-renewal in BC cells ( Wang L. et al, 2015 ). Another study displayed that Gomisin M2 remarkably inhibited BCSCs self-renewal by suppressing the Wnt/β-catenin signaling pathway ( Yang Y. et al, 2019 ). Compared to other cells, the higher level of Wnt/β-catenin signaling pathway contributes to the high resistance level of BCSC.…”

Section: Central Signaling Pathways In Breast Cancer Stem Cellsmentioning

confidence: 99%

The Breast Cancer Stem Cells Traits and Drug Resistance

et al. 2021

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Drug resistance is a major challenge in breast cancer (BC) treatment at present. Accumulating studies indicate that breast cancer stem cells (BCSCs) are responsible for the BC drugs resistance, causing relapse and metastasis in BC patients. Thus, BCSCs elimination could reverse drug resistance and improve drug efficacy to benefit BC patients. Consequently, mastering the knowledge on the proliferation, resistance mechanisms, and separation of BCSCs in BC therapy is extremely helpful for BCSCs-targeted therapeutic strategies. Herein, we summarize the principal BCSCs surface markers and signaling pathways, and list the BCSCs-related drug resistance mechanisms in chemotherapy (CT), endocrine therapy (ET), and targeted therapy (TT), and display therapeutic strategies for targeting BCSCs to reverse drug resistance in BC. Even more importantly, more attention should be paid to studies on BCSC-targeted strategies to overcome the drug resistant dilemma of clinical therapies in the future.

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Gomisin M2 from Baizuan suppresses breast cancer stem cell proliferation in a zebrafish xenograft model

Cited by 27 publications

References 38 publications

Gomisin M2 alleviates psoriasis‑like skin inflammation by inhibiting inflammatory signaling pathways

Gomisin M2 alleviates psoriasis‑like skin inflammation by inhibiting inflammatory signaling pathways

Breast Cancer Stem-Like Cells in Drug Resistance: A Review of Mechanisms and Novel Therapeutic Strategies to Overcome Drug Resistance

The Breast Cancer Stem Cells Traits and Drug Resistance

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