Betulinic acid enhanced the chemical sensitivity of esophageal cancer cells to cisplatin by inducing cell pyroptosis and reducing cell stemness

Chen, Jie; Peng, Rui‑Rui; Niu, Zhenxing; Zhou, Huicong; Kang, Chunyan

doi:10.21037/apm-20-867

Cited by 12 publications

(9 citation statements)

References 16 publications

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“…In esophageal cancer, betulinic acid elicited caspase-1-dependent pyroptosis. Further study demonstrated that the combination of betulinic acid and cisplatin showed stronger growth inhibition than only one alone (84). As a homeostatic degradative process, autophagy is widely involved in regulating tumor cell proliferation and death.…”

Section: The Combined Application Of Pyroptosis Inductors and Other Amentioning

confidence: 98%

“…In the study of cisplatin resistance, overexpression LncRNA ADAMTS9-AS2 could sponge miR-223-3p to activate NLRP3 and trigger pyroptosis in cisplatinresistant cells (83). Chen et al found that both Betulinic acid and cisplatin could elicit the cleavage of caspase-1 in esophageal cancer cells and tissues, and a combination of the two caused more significant cell death (84). PELP1 is a scaffolding oncogenic protein that is closely related to the progression and prognosis of esophageal cancer.…”

Section: Digestive System Tumormentioning

confidence: 99%

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Induction of Pyroptosis: A Promising Strategy for Cancer Treatment

et al. 2021

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Pyroptosis, a lytic pro-inflammatory type of programmed cell death, has been widely studied in diverse inflammatory disease models. Membrane perforation and cell swelling induced by cleaved gasdermin family members is the main characteristic of pyroptosis. Emerging evidence has revealed a complicated relationship between pyroptosis and cancer. On the one hand, as inflammatory cell death, pyroptosis provides a comfortable environment for tumor proliferation. On the other hand, excessive activation of pyroptosis can inhibit the development of tumor cells. In this review, we first summarized the latest progress about the molecular mechanism of pyroptosis. Then, members from gasdermin family, the central molecules of pyroptosis which formed pores on the cell membrane, were highlighted. In the second part of this review, we summarized drugs that induced pyroptosis in different tumors and their concrete mechanisms based on recent literature reports. In the final section, we discussed several hotspots in pyroptosis and cancer therapy, which will point out the direction of sequent research. In brief, inducing pyroptosis in cancer cells is a promising strategy for cancer therapy.

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Section: The Combined Application Of Pyroptosis Inductors and Other Amentioning

confidence: 98%

Section: Digestive System Tumormentioning

confidence: 99%

Induction of Pyroptosis: A Promising Strategy for Cancer Treatment

et al. 2021

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“…Emerging evidence has shown that DDP could induce pyroptotic cell death in various cells 9 , 29 . Enhancing the pyroptotic effect can increase the chemosensitivity to DDP in several cancer cells, including esophageal cancer cells 30 , oesophageal squamous cell carcinoma cells 31 , gastric cancer cells 29 , and non-small cell lung cancer cells 32 . Nevertheless, it is still unclear whether DDP induces TNBC cell pyroptosis.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin Induces Pyroptosis via Activation of MEG3/NLRP3/caspase-1/GSDMD Pathway in Triple-Negative Breast Cancer

Yan¹,

Luo²,

Wu³

et al. 2021

Int. J. Biol. Sci.

140

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Cisplatin (DDP) was reported to improve pathological complete response (pCR) rates in triple-negative breast cancer (TNBC) patients, however, the molecular mechanism still remains largely unknown. Emerging evidence suggested that some chemotherapeutic drugs played anti-tumor effects by inducing cell pyroptosis. Nevertheless, whether pyroptosis contributes to the DDP-induced anti-tumor effect in TNBC remains unexploited. In the present study, NLRP3/caspase-1/GSDMD pyroptosis pathway was involved in the DDP-induced anti-tumor effect of TNBC in vitro and in vivo , providing evidence that DDP might induce pyroptosis in TNBC. Moreover, DDP activated NLRP3/caspase-1/GSDMD pyroptosis pathway by up-regulating the long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3). Furthermore, knockdown of MEG3 not only partly abolished the activation effect of DDP on NLRP3/caspase-1/GSDMD pathway-mediated pyroptosis, but also reversed the suppression of DDP on tumor growth and metastasis ability in vitro and in vivo, further confirming that MEG3 may partially mediate the pyroptotic signaling upon DDP treatment. Thus, our data uncovered a novel mechanism that DDP induced pyroptosis via activation of MEG3/NLRP3/caspase-1/GSDMD pathway in TNBC to exert anti-tumor effects, which may help to develop new strategies for the therapeutic interventions in TNBC.

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“…Inflammasome's dual effects in cancer seem to be dependent on several factors, such as expression, the stage of tumorigenesis, cancer type, and the presence of mutations affecting PRR expression and downstream effector molecules (e.g., IL-1β/18). For EC, a lupine pentacyclic triterpene compound named betulinic acid (BA) was found to induce pyroptosis in ESCC cells by upregulating the protein expression of ASC and caspase-1, resulting in improved sensitivity of ESCC cells to cisplatin, which was further confirmed in vivo [262]. Because this area of study is fairly new in EC research, further studies are needed.…”

Section: Targeting Inflammasomesmentioning

confidence: 94%

Unraveling the Complexity of Regulated Cell Death in Esophageal Cancer: from Underlying Mechanisms to Targeted Therapeutics

Zhang¹,

Zhang²,

Luan³

et al. 2023

Int. J. Biol. Sci.

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Esophageal cancer (EC) is the sixth most common and the seventh most deadly malignancy of the digestive tract, representing a major global health challenge. Despite the availability of multimodal therapeutic strategies, the existing EC treatments continue to yield unsatisfactory results due to their limited efficacy and severe side effects. Recently, knowledge of the subroutines and molecular mechanisms of regulated cell death (RCD) has progressed rapidly, enhancing the understanding of key pathways related to the occurrence, progression, and treatment of many types of tumors, including EC. In this context, the use of small-molecule compounds to target such RCD subroutines has emerged as a promising therapeutic strategy for patients with EC. Thus, in this review, we firstly discussed the risk factors and prevention of EC. We then outlined the established treatment regimens for patients with EC. Furthermore, we not only briefly summarized the mechanisms of five best studied subroutines of RCD related to EC, including apoptosis, ferroptosis, pyroptosis, necroptosis and autophagy, but also outlined the recent advances in the development of small-molecule compounds and long non-coding RNA (lncRNA) targeting the abovementioned RCD subroutines, which may serve as a new therapeutic strategy for patients with EC in the future.

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Betulinic acid enhanced the chemical sensitivity of esophageal cancer cells to cisplatin by inducing cell pyroptosis and reducing cell stemness

Cited by 12 publications

References 16 publications

Induction of Pyroptosis: A Promising Strategy for Cancer Treatment

Induction of Pyroptosis: A Promising Strategy for Cancer Treatment

Cisplatin Induces Pyroptosis via Activation of MEG3/NLRP3/caspase-1/GSDMD Pathway in Triple-Negative Breast Cancer

Unraveling the Complexity of Regulated Cell Death in Esophageal Cancer: from Underlying Mechanisms to Targeted Therapeutics

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