Methyl Linderone Suppresses TPA-Stimulated IL-8 and MMP-9 Expression Via the ERK/STAT3 Pathway in MCF-7 Breast Cancer Cells

Yoon, Jae-Hwan; Pham, Thu-Huyen; Lee, Jintak; Lee, Jiyon; Ryu, Hyung Won; Oh, Sei‐Ryang; Oh, Jae-Wook; Yoon, Do‐Young

doi:10.4014/jmb.1911.11068

Cited by 8 publications

(5 citation statements)

References 26 publications

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“…Our results showed that TMEM9 increased the phosphorylation levels of MEK, ERK, and STAT3. Previous studies have shown that STAT3 is a downstream target of the ERK signaling pathway in various tumors [37][38][39][40]. Consistent with previous findings, we also found that U0126 treatment reduced protein levels of p-STAT3 in TMEM9-overexpressing LUAD cells.…”

Section: Discussionsupporting

confidence: 92%

TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression

Wang,

Zhao,

Tian

et al. 2024

Cell Death Dis

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Abnormal Transmembrane protein 9 (TMEM9) expression has been identified in various human tumors. However, the prognostic potential and mechanistic role of TMEM9 in lung adenocarcinoma (LUAD) remain unclear. Here, we first found a significant upregulation of TMEM9 in LUAD tissues, and TMEM9 expression was positively correlated with microvessel density (MVD), T stage, and clinical stage. Survival analysis demonstrated TMEM9 was an independent indicator of poor prognosis in LUAD patients. In addition, downregulation of TMEM9 suppressed tumor growth and metastasis in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in a cancer cell/HUVEC coculture model. Furthermore, TMEM9 upregulated VEGF expression, and VEGF-neutralizing antibodies reversed HUVEC angiogenesis and cancer cell migration ability caused by overexpression of TMEM9. In contrast, recombinant VEGF (rVEGF) abolished the inhibitory effect of TMEM9-knockdown LUAD cells on HUVEC angiogenesis and tumor cell migration. Moreover, we showed that TMEM9 upregulated VEGF expression by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase/STAT3 (MEK/ERK/STAT3) pathway. Together, our study provides mechanistic insights into the role of TMEM9 in LUAD and highlights the potential of targeting the TMEM9/MEK/ERK/STAT3/VEGF pathway as a novel therapy for preventing LUAD progression.

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Section: Discussionsupporting

confidence: 92%

TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression

Wang,

Zhao,

Tian

et al. 2024

Cell Death Dis

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“…Miconazole suppresses the expression of HIF1α through post-transcriptional regulation in glioma and breast cancer-derived cell lines; this was attributed to the inhibition of mammalian target of rapamycin (mTOR) and regulation of protein synthesis via induction of the phosphorylation of eIF2α, a downstream target of mTOR (Park et al, 2014). In lung cancer cells, miconazole suppresses pSTAT3 Y705 and inhibits the expression of target genes involved in growth, migration, and invasion (Yoon et al, 2020). Further investigations are needed to determine whether miconazole suppresses the 27OHCholinduced cellular responses by acting on the R-Ras, mTOR, or STAT3 pathway.…”

Section: Discussionmentioning

confidence: 99%

Miconazole Suppresses 27-Hydroxycholesterol-induced Inflammation by Regulating Activation of Monocytic Cells to a Proinflammatory Phenotype

Kim

Son²,

Cho³

et al. 2021

Front. Pharmacol.

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Miconazole is effective in treating inflammatory skin conditions and has well-established antifungal effects. To elucidate the underlying mechanisms mediating its additional beneficial effects, we assessed whether miconazole influences the inflammation induced by 27-hydroxycholesterol (27OHChol), an oxygenated cholesterol derivative with high proinflammatory activity, using THP-1 monocytic cells. Miconazole dose-dependently inhibited the expression of proinflammatory markers, including CCL2 and CCR5 ligands such as CCL3 and CCL4, and impaired the migration of monocytic cells and CCR5-positive T cells. In the presence of 27OHChol, miconazole decreased CD14 surface levels and considerably weakened the lipopolysaccharide response. Furthermore, miconazole blocked the release of soluble CD14 and impaired the transcription of the matrix metalloproteinase-9 gene and secretion of its active gene product. Additionally, it downregulated the expression of ORP3 and restored the endocytic function of THP-1 cells. Collectively, these findings indicate that miconazole regulates the 27OHChol-induced expression of proinflammatory molecules in monocytic cells, thereby suppressing inflammation in an oxysterol-rich milieu.

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“…Methyl linderone (ML) ( Figure 4 ) is a cyclo-pentenedione isolated from the fruits of Lindera erythrocarpa (family Lauraceae). Yoon et al [ 195 ] identified that treatment with ML inhibits breast cancer. After performing a cell viability assay, they found that 10 μM is the nontoxic dose of ML.…”

Section: Small-molecule Natural Products As Ras Inhibitorsmentioning

confidence: 99%

Small-Molecule RAS Inhibitors as Anticancer Agents: Discovery, Development, and Mechanistic Studies

Shetu

Bandyopadhyay

2022

IJMS

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Mutations of RAS oncogenes are responsible for about 30% of all human cancer types, including pancreatic, lung, and colorectal cancers. While KRAS1 is a pseudogene, mutation of KRAS2 (commonly known as KRAS oncogene) is directly or indirectly associated with human cancers. Among the RAS family, KRAS is the most abundant oncogene related to uncontrolled cellular proliferation to generate solid tumors in many types of cancer such as pancreatic carcinoma (over 80%), colon carcinoma (40–50%), lung carcinoma (30–50%), and other types of cancer. Once described as ‘undruggable’, RAS proteins have become ‘druggable’, at least to a certain extent, due to the continuous efforts made during the past four decades. In this account, we discuss the chemistry and biology (wherever available) of the small-molecule inhibitors (synthetic, semi-synthetic, and natural) of KRAS proteins that were published in the past decades. Commercial drugs, as well as investigational molecules from preliminary stages to clinical trials, are categorized and discussed in this study. In summary, this study presents an in-depth discussion of RAS proteins, classifies the RAS superfamily, and describes the molecular mechanism of small-molecule RAS inhibitors

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Methyl Linderone Suppresses TPA-Stimulated IL-8 and MMP-9 Expression Via the ERK/STAT3 Pathway in MCF-7 Breast Cancer Cells

Cited by 8 publications

References 26 publications

TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression

TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression

Miconazole Suppresses 27-Hydroxycholesterol-induced Inflammation by Regulating Activation of Monocytic Cells to a Proinflammatory Phenotype

Small-Molecule RAS Inhibitors as Anticancer Agents: Discovery, Development, and Mechanistic Studies

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