Saikosaponin D Inducing Apoptosis and Autophagy through the Activation of Endoplasmic Reticulum Stress in Glioblastoma

Liu, Guimei; Guan, Yuehong; Liu, Yongxian; Wang, Yaping; Liu, Yusi; Liu, Xiaobin

doi:10.1155/2022/5489553

Cited by 5 publications

(5 citation statements)

References 42 publications

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“…Furthermore, we showed that SSd attenuated cerulein‐induced pyroptosis and established the correlations between the inhibition of pyroptosis and mitigation of inflammatory injury in PACs. Actually, some other programmed cell death forms including autophagy and apoptosis have been found to be involved in the effects of SSd on cells under different pathophysiological circumstances (Liu et al, 2022; Zeng et al, 2023). Our current findings provided new insights into how SSd affected cell fate implicated in disease management.…”

Section: Discussionmentioning

confidence: 99%

Saikosaponin d protects pancreatic acinar cells against cerulein‐induced pyroptosis through alleviating mitochondrial damage and inhibiting cGAS‐STING pathway

Chen,

Lu,

et al. 2024

J of Applied Toxicology

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Acute pancreatitis represents an inflammatory disease featuring pancreatic necrosis and inflammation. Inflammatory injury of pancreatic acinar cells (PACs) is critically involved in the initiation and progression of acute pancreatitis. Pyroptosis, a new kind of programmed cell death concomitant with a low‐grade inflammatory reaction, plays a function in acute pancreatitis pathology. It is unclear whether saikosaponin d (SSd), a pharmacologically active natural product, could protect PACs by regulating pyroptosis. Here, we established a PAC injury model in vitro using cerulein to treat AR42J cells. SSd restored viability and proliferation and lowered the release of pancreatic enzymes and inflammatory interleukins in cerulein‐treated AR42J cells. Cerulein‐induced pyroptosis was evidenced by typical ultrastructural changes and NLRP3/caspase‐1 activation in AR42J cells, but SSd attenuated cerulein‐induced pyroptosis and inhibited NLRP3/caspase‐1 pathway. Mechanically, SSd reduced mitochondrial damage and mtDNA release, and blocked cGAS‐STING signaling in AR42J cells treated with cerulein, contributing to the inhibition of NLRP3‐mediated pyroptosis. Furthermore, SSd abolished cerulein‐elevated oxidative stress in AR42J cells, leading to the mitigation of mitochondrial damage and inhibition of cGAS‐STING signaling and pyroptosis. In conclusion, SSd protected PACs against cerulein‐induced pyroptosis by alleviating mitochondrial damage and inhibiting the cGAS‐STING pathway, and it could be a therapeutic candidate for acute pancreatitis.

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Section: Discussionmentioning

confidence: 99%

Saikosaponin d protects pancreatic acinar cells against cerulein‐induced pyroptosis through alleviating mitochondrial damage and inhibiting cGAS‐STING pathway

Chen,

Lu,

et al. 2024

J of Applied Toxicology

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“…Then, cell viability was calculated. According to the experimental results, two low-concentration TMZ groups (50 µM [T50] and 100 µM [T100]) were selected to be combined with the two concentrations (9 µM [S9] and 12 µM [S12)) of the cytotoxic effect of SSD on GBM that we studied before [22] , namely T50/S9, T50/S12, T100/S9, and T100/S12 (Table 1).…”

Section: Tmz Sensitivity Analysis and Cell Viability Assaymentioning

confidence: 99%

“…The result was rated as negative (−) when no immunolabeling was observed in target cells, weakly positive (+) when the labeling was faint, and moderately positive (+) or strongly positive (>++) when the labeling was stronger or distinctly stronger than (++). This procedure was performed as per the methods described by Guimei Liu et al in 2022 [22] .…”

Section: Immunocytochemical Stainingmentioning

confidence: 99%

Saikosaponin D Increases Temozolomide Sensitivity of Glioblastoma via ER Stress-Induced Apoptosis and Autophagy

Liu

Zheng

et al. 2023

Preprint

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Background: Glioblastoma multiforme (GBM) is a primary aggressive brain tumor with high morbidity and mortality. Temozolomide (TMZ) has been applied to the treatment of GBM for over a decade, but TMZ resistance is a major obstacle to preventing the recurrence of GBM after surgery. In this study, the effect of Saikosaponin D (SSD) on increasing TMZ sensitivity was investigated by activating the endoplasmic reticulum (ER) stresspathway. Methods: Three GBM cell lines with different sensitivities were selected, including rat RG-2 cells, human U251 cells, and LN-428 cells. Cell viability was detected by the Cell Counting Kit-8 (CCK-8) assay and the plate cloning assay method. Cell morphology was observed by hematoxylin and eosin (HE) staining. The apoptosis and autophagy of GBM cells were determined by Hoechst 33258 and MDC fluorescent staining. The expression and distribution of ER stress proteins (GRP78, CHOP, PERK and ATF6) were detected by Western blotting (WB) and immunocytochemistry (ICC). Meanwhile, the expression and distribution of apoptosis proteins (Caspase-12, Caspase-9, and Caspase-3) and autophagy proteins (Beclin-1 and LC3) were also examined by WB and ICC. Results: The CCK-8 proliferation experiment and HE staining results confirmed that TMZ could inhibit the proliferation of GBM cells with the increase of the treatment time and dose. The highest inhibition rate was observed in RG-2 cells, while LN-428 cells exhibited poor sensitivity. Besides, the combined treatment with SSD and TMZ (SSD+TMZ) significantly promoted the apoptosis of GBM cells, compared with single drug administration groups. In addition, the WB experiment results suggested that the expression of ER stress-related proteins (PERK, ATF6, GRP78, and CHOP) was up-regulated. Moreover, apoptotic bodies and damaged nuclei were observed under Hoechst 3328 staining in the SSD+TMZ treatment group. Furthermore, the WB results revealed that Caspase-3, Caspase-9, and Caspase-12 were cleaved, and the expression of these cleaved bodies was up-regulated after the SSD+TMZ treatment. Autophagosomes were observed under MDC staining, and the expression of autophagy proteins (LC3 and Beclin-1) was up-regulated. These results indicated that SSD enhanced TMZ sensitivity of GBM cells via ER stress-induced apoptosis and autophagy.

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Section: Introductionmentioning

confidence: 99%

“…Saikosaponin D (SSD) is a main bioactive component of the herbal medicine Radix bupleuri and possesses various pharmacological activities, such as anti‐inflammatory, anti‐cancer and metabolic regulation. 8 , 9 , 10 Previous reports suggested that SSA, the epimer of SSD, alleviates lipopolysaccharide (LPS)‐evoked ALI in a mouse model. 11 Wang et al demonstrated that SSD improves mechanical ventilation‐triggered lung injury in rat models by alleviating inflammation, apoptosis and oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Saikosaponin D attenuates inflammatory response and cell apoptosis of lipopolysaccharide‐induced lung epithelial cells

Song,

Lu,

Tao

2023

Clinical Respiratory J

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BackgroundAcute lung injury (ALI) is a prevalent complication of sepsis with high mortality rate. Saikosaponin D (SSD) is a triterpenoid saponin that has been reported to alleviate sepsis‐triggered renal injury in mice. Nonetheless, the therapeutic effect of SSD on sepsis‐evoked ALI is unclarified.MethodsLipopolysaccharide (LPS) from Escherichia coli 055:B5 was utilized to stimulate lung epithelial cell line MLE‐12. A mouse model of sepsis was established. CCK‐8 assay was employed for determining cytotoxicity. ELISA was utilized for determining proinflammatory cytokine production. Flow cytometry and western blotting were implemented for evaluating cell apoptosis. Hematoxylin–eosin staining was conducted for histologic analysis of murine lung tissues.ResultsSSD alleviated LPS‐triggered inflammation and cell apoptosis of MLE‐12 cells. SSD treatment ameliorated the pathological damages, inflammatory response, and cell apoptosis in the lungs of septic mice.ConclusionSSD protects against sepsis‐triggered ALI by inhibiting inflammation and cell apoptosis in MLE‐12 cells and septic mouse mice.

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Saikosaponin D Inducing Apoptosis and Autophagy through the Activation of Endoplasmic Reticulum Stress in Glioblastoma

Cited by 5 publications

References 42 publications

Saikosaponin d protects pancreatic acinar cells against cerulein‐induced pyroptosis through alleviating mitochondrial damage and inhibiting cGAS‐STING pathway

Saikosaponin d protects pancreatic acinar cells against cerulein‐induced pyroptosis through alleviating mitochondrial damage and inhibiting cGAS‐STING pathway

Saikosaponin D Increases Temozolomide Sensitivity of Glioblastoma via ER Stress-Induced Apoptosis and Autophagy

Saikosaponin D attenuates inflammatory response and cell apoptosis of lipopolysaccharide‐induced lung epithelial cells

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