Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway

Lv, Xingyu; Lin, Yuqi; Zhu, Xi; Cai, Xiujun

doi:10.1080/13880209.2023.2191645

Cited by 7 publications

(3 citation statements)

References 39 publications

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“…The MAPK family plays an important role in regulating the proliferation, differentiation, transformation, apoptosis, and metabolism of malignant tumours 23 , 24 . MAPK signalling is also involved in the occurrence and development of a variety of cancers, indicating its important role in tumour biological processes such as cancer cell proliferation, apoptosis, and differentiation 25 , 26 . The extracellular regulated protein kinase (ERK1/2) family was the first classic MAPK signal transduction pathway to be discovered, and includes Ras, RAF, and MAPK.…”

Section: Discussionmentioning

confidence: 99%

Parthenolide induces gallbladder cancer cell apoptosis via MAPK signaling

Obulkasim,

Aji,

Abudoula

et al. 2024

Annals of Medicine &Amp; Surgery

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Objective Parthenolide (PTL) has a wide range of clinical applications owing to its anti-inflammatory and antitumor effects. To date, the antitumor effect of PTL on gallbladder cancer (GBC) remains largely unknown. Therefore, we aimed to investigate the biological effects of PTL on GBC. Methods: The cellular viability and proliferation of GBC-SD and NOZ cell lines after treatment with different concentrations of PTL were analyzed using the Cell Counting Kit-8( CCK8 )assay and colony formation assay. Apoptosis analysis was performed using flow cytometry. Hoechst staining was performed. RNA sequencing (RNA-seq) was performed to identify PTL-related genes and signaling pathways. Furthermore, we confirmed the involvement of these signaling pathways by qRT-PCR and western blotting. For the in vivo experiments, a xenograft model was used to evaluate the effects of PTL on the proliferation of NOZ cells. Results: PTL significantly inhibited GBC cell growth in vitro and induced apoptosis in the GBC-SD and NOZ cell lines in a dose-dependent manner. RNA sequencing data showed that the immune response and mitogen-activated protein kinase (MAPK) signaling pathways are closely associated with PTL-induced gallbladder cancer cell apoptosis. PTL upregulated BAX, Cleaved PARP-1, Cleaved Caspase-3, Cleaved Caspase-9, P53 and decreased the expression of BCL-2, phosphorylated ERK, and phosphorylated MEK in vitro. Tumor volume and weight were also suppressed by PTL in vivo. Moreover, the effects of PTL on GBC cells might be mediated by the MAPK pathway. Conclusion PTL significantly inhibits gallbladder cancer cell proliferation and induces apoptosis through the MAPK pathway, which is a potential molecular reagent for treating GBC. However, further exploration is needed to verify the antitumor effects of PTL and its intracellular signaling mechanism.

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Section: Discussionmentioning

confidence: 99%

Parthenolide induces gallbladder cancer cell apoptosis via MAPK signaling

Obulkasim,

Aji,

Abudoula

et al. 2024

Annals of Medicine &Amp; Surgery

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“…We also studied the possible mechanisms of their action using in vitro and in silico molecular screening methods. Thus, to date, the therapeutic potential of isoalantolactone has been convincingly demonstrated in the treatment of bladder [36] and endometrial cancer [37], colorectal carcinoma [38], liver cancer [39], breast cancer [40], etc. [41,42], due to its influence on a wide range of signaling pathways and pathological cascades that play a critical role in the progression of malignant neoplasms.…”

Section: Introductionmentioning

confidence: 99%

“…The ability of dehydrocoslactone to suppress cancer progression by inhibiting migration [47], proliferation, epithelial-mesynchemic transition [48], sub-G1 cell cycle arrest, DNA damage, and loss of mitochondrial membrane potential [49] has been widely described. Thus, to date, the therapeutic potential of isoalantolactone has been convincingly demonstrated in the treatment of bladder [36] and endometrial cancer [37], colorectal carcinoma [38], liver cancer [39], breast cancer [40], etc. [41,42], due to its influence on a wide range of signaling pathways and pathological cascades that play a critical role in the progression of malignant neoplasms.…”

Section: Introductionmentioning

confidence: 99%

Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells

Neganova,

Aleksandrova,

Sharova

et al. 2024

Molecules

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In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.

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Saffron regulates bile acid metabolism and participates in the molecular mechanisms of cholestasis-induced liver injury through the mediation of the ERK signaling pathway

Wang,

Xiong,

et al. 2024

Journal of Functional Foods

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Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway

Cited by 7 publications

References 39 publications

Parthenolide induces gallbladder cancer cell apoptosis via MAPK signaling

Parthenolide induces gallbladder cancer cell apoptosis via MAPK signaling

Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells

Saffron regulates bile acid metabolism and participates in the molecular mechanisms of cholestasis-induced liver injury through the mediation of the ERK signaling pathway

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