Inhibitory effect of ginsenoside Rg3 on cancer stemness and mesenchymal transition in breast cancer via regulation of myeloid-derived suppressor cells

Song, Joong-Hyun; Eum, Da-Young; Park, Soon-Yong; Jin, Yunho; Shim, Jae-Woong; Park, Shin-Ji; Kim, Minyoung; Park, Seongjun; Heo, Kyu; Choi, Yoo-Jin

doi:10.1371/journal.pone.0240533

Cited by 25 publications

(15 citation statements)

References 34 publications

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“…It has been shown that the expansion of MDSCs correlates with tumor burden of BC-bearing patients, and the alteration of MDSC-tumor interaction is considered a promising strategy to combat this disease [242] . Consistently with this observation, Peng et al [243] demonstrated that MDSCs accelerate tumor progression and increase tumor incidence in NOD-scid IL2Rγ null (NSG) mice in vivo. To dissect the underlying molecular mechanism, they observed that MDSCs promote and sustain BCSCs by regulating the crosstalk between STAT3 and Notch signaling in tumor cells.…”

Section: Disrupting Notch-dependent Tumor and Immune Cells Interaction To Overcome Drug Resistancementioning

confidence: 53%

“…Indeed, MDSCs secretes IL-6, which induces STAT3 phosphorylation, and activates Notch signaling, which enforces IL-6/STAT3 activation, thereby affecting cancer stemness. Interestingly, the inhibition of these two pathways decreased tumor incidence in vivo [243] .…”

Section: Disrupting Notch-dependent Tumor and Immune Cells Interaction To Overcome Drug Resistancementioning

confidence: 98%

“…More recently, Song et al [ 244 ] made a step forward linking Notch-mediated MDSC-tumor interaction to drug resistance. By testing the main active component extracted from ginseng (Rg3), the authors documented that the natural compound effectively hampers MDSCs expansion, and this correlates with Notch and STAT3 signaling pathways’ down-modulation, which in turn suppresses cancer stemness and EMT in vitro and in vivo .…”

Section: Notch Signaling and Tmementioning

confidence: 99%

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Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Giuli¹,

Mancusi²,

Giuliani³

et al. 2021

CDR

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Drug resistance is one of the main challenges in cancer therapy, including in the treatment of female-specific malignancies, which account for more than 60% of cancer cases among women. Therefore, elucidating the underlying molecular mechanisms is an urgent need in gynecological cancers to foster novel therapeutic approaches. Notably, Notch signaling, including either receptors or ligands, has emerged as a promising candidate given its multifaceted role in almost all of the hallmarks of cancer. Concerning the connection between Notch pathway and drug resistance in the afore-mentioned tumor contexts, several studies focused on the Notchdependent regulation of the cancer stem cell (CSC) subpopulation or the induction of the epithelial-tomesenchymal transition (EMT), both features implicated in either intrinsic or acquired resistance. Indeed, the present review provides an up-to-date overview of the published results on Notch signaling and EMT-or CSCdriven drug resistance. Moreover, other drug resistance-related mechanisms are examined such as the involvement of the Notch pathway in drug efflux and tumor microenvironment. Collectively, there is a long way to go before every facet will be fully understood; nevertheless, some small pieces are falling neatly into place. Overall, the main aim of this review is to provide strong evidence in support of Notch signaling inhibition as an effective strategy to evade or reverse resistance in female-specific cancers.

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Section: Disrupting Notch-dependent Tumor and Immune Cells Interaction To Overcome Drug Resistancementioning

confidence: 53%

Section: Disrupting Notch-dependent Tumor and Immune Cells Interaction To Overcome Drug Resistancementioning

confidence: 98%

Section: Notch Signaling and Tmementioning

confidence: 99%

See 1 more Smart Citation

Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Giuli¹,

Mancusi²,

Giuliani³

et al. 2021

CDR

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“…Meanwhile, Rg3 has been well-described as a tumor suppressor of breast cancer. It has been found that ginsenoside Rg3 reduces mesenchymal transition and cancer stemness of breast cancer by regulating myeloid-related suppressor cells [ 24 ]. Ginsenoside Rg3 combined with Endostar represses tumor growth of breast cancer cells [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Carbon nanotubes (CNT)-loaded ginsenosides Rb3 suppresses the PD-1/PD-L1 pathway in triple-negative breast cancer

Luo

Wang

2021

Aging

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Carbon nanotubes (CNTs), as advanced nanotechnology with specific properties and structures, have presented practical drug delivery properties. Ginsenoside Rg3 is a component of puffed ginseng and demonstrates anti-cancer activities. To explore the effect of CNTs-loaded Rg3 (Rg3-CNT) on the PD-1/PD-L1 signaling and the development of triple-negative breast cancer (TNBC). Our data revealed that Rg3 inhibited the cell viability of TNBC cells, in which Rg3-CNT further enhanced this effect in the system. Similarly, the colony formation of TNBC cells was decreased by Rg3, while Rg3-CNT could reinforce its effect in the cells. Besides, the treatment of Rg3 induced apoptosis of TNBC cells, in which Rg3-CNT treatment further increased the phenotype in the cells. Remarkably, Rg3-CNT, but not Rg3, attenuated PD-L1 expression in TNBC cells. Rg3-CNT decreased the PD-L1 upregulation induced by interferon-γ (IFN-γ) in breast cancer cells. Importantly, Rg3-CNT was able to reduce PD-1 expression in activated T cells. Specifically, Rg3-CNT reduced the PD-1/PD-L1 axis in a T cell/triple-negative TNBC cell co-culture system. Moreover, the levels of IFN-γ, interleukins-2 (IL-2), interleukins-9 (IL-9), interleukins-10 (IL-10), interleukins-22 (IL-22), and interleukins-23 (IL-23) were significantly stimulated in the activated T cells, while the treatment of Rg3-CNT could reverse these phenotypes in the cells. Rg3-CNT attenuated the TNBC cell growth in vivo. The Rg3-CNT improved the anti-cancer effect of Rg3 toward TNBC by inhibiting the PD-1/PD-L1 axis. Our finding provides new insights into the mechanism by which Rg3-CNT attenuates the development of TNBC. Rg3-CNT may be applied as the potential therapeutic strategy for immunotherapy of TNBC.

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“…Ginsenoside Rg3 serves as a primary ginseng component and presents angiogenesis inhibitory potential in conventional biomedicine (Ahmmed et al, 2019). Rg3 exhibits anti-tumor properties in various cancer models, including lung cancer, breast cancer, and ovarian cancer (Sun et al, 2017;Song et al, 2020). Rg3 has been found to induce apoptosis and repress migration of cancer stem cells (Tang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Graphene Oxide Nanoparticle–Loaded Ginsenoside Rg3 Improves Photodynamic Therapy in Inhibiting Malignant Progression and Stemness of Osteosarcoma

Wang

Liu

et al. 2021

Front. Mol. Biosci.

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Osteosarcoma serves as a prevalent bone cancer with a high metastasis and common drug resistance, resulting in poor prognosis and high mortality. Photodynamic therapy (PDT) is a patient-specific and non-invasive tumor therapy. Nanoparticles, like graphene oxide have been widely used in drug delivery and PDT. Ginsenoside Rg3 is a principal ginseng component and has presented significant anti-cancer activities. Here, we constructed the nanoparticles using GO linked with photosensitizer (PS) indocyanine green (ICG), folic acid, and polyethylene glycol (PEG), and loaded with Rg3 (PEG–GO–FA/ICG–Rg3). We aimed to explore the effect of PEG–GO–FA/ICG–Rg3 combined with PDT for the treatment of osteosarcoma. Significantly, we found that Rg3 repressed proliferation, invasion, and migration, and enhanced apoptosis and autophagy of osteosarcoma cells, while the PEG–GO–FA/ICG–Rg3 presented a higher activity, in which NIR laser co-treatment could remarkably increase the effect of PEG–GO–FA/ICG–Rg3. Meanwhile, stemness of osteosarcoma cell–derived cancer stem cells was inhibited by Rg3 and PEG–GO–FA/ICG–Rg3, and the combination of PEG–GO–FA/ICG–Rg3 with NIR laser further significantly attenuated this phenotype in the system. Moreover, NIR laser notably improved the inhibitor effect of PEG–GO–FA/ICG–Rg3 on the tumor growth of osteosarcoma cells in vivo. Consequently, we concluded that PEG–GO–FA/ICG–Rg3 improved PDT in inhibiting malignant progression and stemness of osteosarcoma cell. Our finding provides a promising and practical therapeutic strategy for the combined treatment of osteosarcoma.

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Inhibitory effect of ginsenoside Rg3 on cancer stemness and mesenchymal transition in breast cancer via regulation of myeloid-derived suppressor cells

Cited by 25 publications

References 34 publications

Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Carbon nanotubes (CNT)-loaded ginsenosides Rb3 suppresses the PD-1/PD-L1 pathway in triple-negative breast cancer

Graphene Oxide Nanoparticle–Loaded Ginsenoside Rg3 Improves Photodynamic Therapy in Inhibiting Malignant Progression and Stemness of Osteosarcoma

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