Eucannabinolide, a novel sesquiterpene lactone, suppresses the growth, metastasis and BCSCS-like traits of TNBC via inactivation of STAT3

Zhu, Zhihui; Yuan, Jingtao; Xu, Xintong; Wei, Yingying; Yang, Bo; Zhao, Huajun

doi:10.1016/j.neo.2020.10.012

Cited by 12 publications

(5 citation statements)

References 34 publications

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“…SRC-mediated cellular signaling can affect the proliferation, survival, migration, and invasion of TNBC cells [27]. In TNBC, suppression of STAT3 expression inhibited tumor proliferation and migration [28]. Additionally, HRAS [29] and MAPK1 [30] levels were significantly increased in TNBC patients.…”

Section: Discussionmentioning

confidence: 99%

Erianin inhibits the progression of triple-negative breast cancer by suppressing SRC-mediated cholesterol metabolism

Li,

Kang,

Deng

et al. 2024

Cancer Cell Int

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Triple-negative breast cancer (TNBC) is highly malignant and lacks effective biotherapeutic targets. The development of efficient anticancer drugs with low toxicity and few side effects is a hotspot in TNBC treatment research. Although erianin is known to have potent antitumor activity, its regulatory mechanism and target in TNBC have not been fully elucidated, hampering further drug development. This study showed that erianin can significantly inhibit TNBC cell proliferation and migration, promote cell apoptosis, and inhibit the growth of transplanted tumors in mice. Mechanistically, through network pharmacology analysis, molecular docking and cellular thermal shift assays, we preliminarily identified SRC as the cellular target of erianin. Erianin potently inhibited the expression of SRC, which mediated the anticancer effect of erianin in TNBC. Moreover, erianin can downregulate the expression of genes related to cholesterol synthesis and uptake by targeting SRC, interfering with cholesterol levels in TNBC, thereby inhibiting the progression of TNBC in vivo and in vitro. Taken together, our results suggest that erianin may inhibit the progression of TNBC by suppressing SRC-mediated cholesterol metabolism, and erianin has the great potential to be an effective treatment for TNBC patients.

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Section: Discussionmentioning

confidence: 99%

Erianin inhibits the progression of triple-negative breast cancer by suppressing SRC-mediated cholesterol metabolism

Li,

Kang,

Deng

et al. 2024

Cancer Cell Int

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“…Research has identified a wide array of small molecules that exhibit the potential to inhibit TNBC cell viability. This includes Dihydrotanshinone ( 166 ), DT-13 ( 167 ), Cucurbitacin E ( 168 – 170 ), Niclosamide ( 171 – 173 ), SG-1709 ( 174 ), SG-1721 ( 174 ), Nifuroxazide ( 175 , 176 ), LLY17 ( 177 ), 6Br-6a ( 178 ), Pyrimethamine ( 179 , 180 ), Pectolinarigenin ( 181 ), Flubendazole ( 182 , 183 ), Eupalinolide J ( 184 , 185 ), Betulinic acid ( 186 ), Carfilzomib ( 187 ), WP1066 ( 188 ), Rhus coriaria extract ( 189 ), FZU-03,010 ( 190 ), Disulfiram ( 191 ), Schisandrin B ( 192 ), Osthole ( 193 ), Brevilin A ( 194 ), Arnicolide D ( 195 ), Eucannabinolide ( 196 ), Pulvomycin ( 197 ), R001 ( 198 ), Salinomycin ( 199 , 200 ), the ethanolic extract of origanum syriacum ( 201 ), Apigenin ( 202 ), and AG-014699 ( 203 ). This inhibition is attributed to their ability to suppress STAT3 phosphorylation.…”

Section: Current Therapeutic Applications Of the Jak2/stat3 Signaling...mentioning

confidence: 99%

Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer

Long,

Fei,

Chen

et al. 2024

Front. Oncol.

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Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its propensity for metastasis and poor prognosis. TNBC evades the body’s immune system recognition and attack through various mechanisms, including the Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. This pathway, characterized by heightened activity in numerous solid tumors, exhibits pronounced activation in specific TNBC subtypes. Consequently, targeting the JAK2/STAT3 signaling pathway emerges as a promising and precise therapeutic strategy for TNBC. The signal transduction cascade of the JAK2/STAT3 pathway predominantly involves receptor tyrosine kinases, the tyrosine kinase JAK2, and the transcription factor STAT3. Ongoing preclinical studies and clinical research are actively investigating this pathway as a potential therapeutic target for TNBC treatment. This article comprehensively reviews preclinical and clinical investigations into TNBC treatment by targeting the JAK2/STAT3 signaling pathway using small molecule compounds. The review explores the role of the JAK2/STAT3 pathway in TNBC therapeutics, evaluating the benefits and limitations of active inhibitors and proteolysis-targeting chimeras in TNBC treatment. The aim is to facilitate the development of novel small-molecule compounds that target TNBC effectively. Ultimately, this work seeks to contribute to enhancing therapeutic efficacy for patients with TNBC.

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“…On the one hand, chemotherapeutic drugs could promote the cleavage of gasdermin E (GSDME) by activating Caspase-3, to transform apoptosis into pyroptosis and promote tumor cell death [ 256 , 257 ]. Likewise, tetraarsenic hexoxide (As 4 O 6 ) could inhibit the phosphorylation of mitochondrial STAT3 and activate mitochondrial ROS-mediated GSDME pathway, to induce pyroptotic cell death in TNBC cells, and finally inhibit tumor growth and metastasis of TNBC [ 258 , 259 ]. On the other hand, chemotherapeutic drugs also played an anti-TNBC role by inducing pyroptosis [ 260 ].…”

Section: Targeting Other Rcd Subroutines With Small-molecule Compound...mentioning

confidence: 99%

Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

et al. 2022

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Triple-negative breast cancer (TNBC) is a subtype of human breast cancer with one of the worst prognoses, with no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed cell death (PCD), has been widely reported to have numerous links to the progression and therapy of many types of human cancer. Of note, RCD can be divided into numerous different subroutines, including autophagy-dependent cell death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis and anoikis. More recently, targeting the subroutines of RCD with small-molecule compounds has been emerging as a promising therapeutic strategy, which has rapidly progressed in the treatment of TNBC. Therefore, in this review, we focus on summarizing the molecular mechanisms of the above-mentioned seven major RCD subroutines related to TNBC and the latest progress of small-molecule compounds targeting different RCD subroutines. Moreover, we further discuss the combined strategies of one drug (e.g., narciclasine) or more drugs (e.g., torin-1 combined with chloroquine) to achieve the therapeutic potential on TNBC by regulating RCD subroutines. More importantly, we demonstrate several small-molecule compounds (e.g., ONC201 and NCT03733119) by targeting the subroutines of RCD in TNBC clinical trials. Taken together, these findings will provide a clue on illuminating more actionable low-hanging-fruit druggable targets and candidate small-molecule drugs for potential RCD-related TNBC therapies. Graphical abstract

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Eucannabinolide, a novel sesquiterpene lactone, suppresses the growth, metastasis and BCSCS-like traits of TNBC via inactivation of STAT3

Cited by 12 publications

References 34 publications

Erianin inhibits the progression of triple-negative breast cancer by suppressing SRC-mediated cholesterol metabolism

Erianin inhibits the progression of triple-negative breast cancer by suppressing SRC-mediated cholesterol metabolism

Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer

Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

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