Jolkinolide B sensitizes bladder cancer to mTOR inhibitors via dual inhibition of Akt signaling and autophagy

Sang, Jun; Gan, Liu; Zou, Ming-Feng; Lin, Zi-Jun; Fan, Run-Zhu; Huang, Jia-Luo; Li, Wei; Yin, Sheng

doi:10.1016/j.canlet.2021.11.014

Cited by 21 publications

(17 citation statements)

References 38 publications

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“…Although polycyclic diterpenes were not the characteristic components of Euphorbia plants, some polycyclic diterpenes showed great potential in the development of anticancer drugs [ 16 , 17 , 18 ]. Jolkinolide B, a typical ent -abietane diterpene first isolated from Euphorbia jolkini , induced apoptosis and sensitized bladder cancer to mTOR inhibitors [ 19 , 20 ]; 17-hydroxy-jolkinolide B, a potent inhibitor of JAK/STAT3 signaling, is a promising anticancer drug candidate [ 21 ]. In this study, compounds 1 – 2 sharing the same abietane diterpene skeleton (6/6/6 carbon ring system) were shown to be promising anti-prostate cancer candidates.…”

Section: Resultsmentioning

confidence: 99%

Ent-Abietane Diterpenoids from Euphorbia fischeriana and Their Cytotoxic Activities

Zhu

Liao

et al. 2022

Molecules

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The roots of Euphorbia fischeriana have been used as a traditional Chinese medicine for the treatment of tuberculosis and ringworm. In the current study, diterpenoids from the ethyl acetate extract of the roots E. fischeriana and their cytotoxic effects against five cancer lines were investigated. Two new ent-abietane diterpenoids, euphonoids H and I (1–2), as well as their two analogues (3–4) were first isolated from this source. The structures of the two new compounds were elucidated on the basis of spectroscopic data and quantum chemical calculation. Their absolute configurations were assigned via ECD spectrum calculation. The isolated compounds were evaluated for their antiproliferative activities against five cancer cell lines. Compounds 1 and 2 exhibited significant inhibitory effects against human prostate cancers C4-2B and C4-2B/ENZR cell lines with IC50 values ranging from 4.16 ± 0.42 to 5.74 ± 0.45 μM.

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Section: Resultsmentioning

confidence: 99%

Ent-Abietane Diterpenoids from Euphorbia fischeriana and Their Cytotoxic Activities

Zhu

Liao

et al. 2022

Molecules

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“…Moreover, we also created some possible chemotherapy regimens for patients in the high-CRS subgroup. Although there are reports about the use of mammalian target of rapamycin (mTOR) inhibitors in BLCA, they have had limited success in clinical practice because of the simultaneous activation of compensatory pathways [ 41 ]. Our study provides an accurate guide for the use of mTOR inhibitors in patients with BLCA tumours.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Common Serum Response Signature-Related Classification Affects the Tumour Microenvironment and Predicts Prognosis in Bladder Cancer

Yang

Zhou

Huang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Abnormal oncogenic signatures provide important clues regarding cancer prognosis and treatment. We analysed the variations in 189 oncogenic signature gene sets between normal and tumourous tissues from The Cancer Genome Atlas (TCGA) and found that the “CSR_LATE_UP” signature was the most upregulated oncogenic signature gene set in bladder cancer. Next, we developed a common serum response (CSR) risk score (CRS) model based on fibroblast CSR genes and systematically analysed the correlations of these genes or the CRSs with survival, previously reported molecular subtypes, clinicopathological features, cancer signalling pathways, chemotherapeutic responses, and the tumour microenvironment using TCGA and validation cohorts. The CRS could predict the malignant phenotype, chemotherapeutic efficacy, immune invasion, and disease prognosis. Inflammatory signalling pathways (e.g., inflammatory response, TNFA signalling via NFƘB, IFNα response, and IL2-STAT5 signalling) were markedly upregulated in patients with high CRS. Notably, the CSR-related gene ANLN was positively correlated with CD8+ immune cell infiltration, PD-L1 expression, and sensitivity to PD-L1 inhibitors and could thus provide guidance for clinical immunotherapy. This study highlights the crucial role of the CSR signature in bladder cancer and provides a CRS model for accurate predictions of the disease prognosis and chemotherapy and immunotherapy responses.

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“…Furthermore, K14 could induce the dual inhibition of AKT feedback activation and cytoprotective autophagy, potentiating the antiproliferative efficacy of mTOR inhibitors in both PTEN-deficient and cisplatin-resistant bladder cancers in vitro and in vivo . 287 Collectively, K14 is a promising candidate in future anticancer drug development.…”

Section: Biological Activitiesmentioning

confidence: 99%

Euphorbiaditerpenoids: isolation, structure, bioactivity, biosynthesis, and synthesis (2013–2021)

et al. 2022

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Jolkinolide B sensitizes bladder cancer to mTOR inhibitors via dual inhibition of Akt signaling and autophagy

Cited by 21 publications

References 38 publications

Ent-Abietane Diterpenoids from Euphorbia fischeriana and Their Cytotoxic Activities

Ent-Abietane Diterpenoids from Euphorbia fischeriana and Their Cytotoxic Activities

Fibroblast Common Serum Response Signature-Related Classification Affects the Tumour Microenvironment and Predicts Prognosis in Bladder Cancer

Euphorbiaditerpenoids: isolation, structure, bioactivity, biosynthesis, and synthesis (2013–2021)

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