Silibinin stimluates apoptosis by inducing generation of ROS and ER stress in human choriocarcinoma cells

Ham, Jiyeon; Lim, Whasun; Bazer, Fuller W.; Song, Gwonhwa

doi:10.1002/jcp.26069

Cited by 28 publications

(15 citation statements)

References 37 publications

(42 reference statements)

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“…Following induction of GRP78, ER stress signals lead to activation of ATF4/CHOP, which has been reported to sensitize cells to apoptosis [33]. Similar to the above results, silibinin-induced ER stress-dependent apoptosis in choriocarcinoma cells is closely related to the GRP78 signaling pathways [34]. It has also been reported that CHOP, the ER stress-induced transcription factor, not only down-regulates Bcl-2 expression, but also leads to translocation of Bax from the cytosol to the mitochondria [35].…”

Section: Discussionsupporting

confidence: 72%

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

Lin

Lee

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Protodioscin (PD) is a steroidal saponin with anti-cancer effects on a number of cancer cells, but the anti-tumor effects and mechanism of action of PD on human cervical cancer cells is unclear. Methods: We determined cell viability using the MTT assay. Cell death, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) generation, and endoplasmic reticulum (ER) stress were measured on a flow cytometry. Caspase activation, ER stress, and MMP-dependent apoptosis proteins in cervical cancer cells in response to PD were determined by Western blot analysis. The ability of ATF4 binding to ChIP promoter was measured using the ChIP assay. Results: We demonstrated that PD inhibits cell viability, causes a loss of mitochondrial function, and induces apoptosis, as evidenced by up-regulation of caspase-8, -3, -9, -PARP, and Bax activation, and down-regulation of Bcl-2 expression. PD was shown to induce ROS and the ER stress pathway, including GRP78, p-eIF-2α, ATF4, and CHOP. Pre-treatment with NAC, a ROS production inhibitor, significantly reduced ER stress and apoptosis-related proteins induced by PD. Transfection of GRP78/CHOP-siRNA effectively inhibited PD-induced ER stress-dependent apoptosis. Moreover, treatment with PD significantly increased p38 and JNK activation. Co-administration of a JNK inhibitor (SP600125) or p38 inhibitor (SB203580) abolished cell death and ER stress effects during PD treatment. In addition, PD induced the expression of nuclear ATF4 and CHOP, as well as the binding ability of ATF4 to the CHOP promoter. Conclusion: Our results suggest that PD is a promising therapeutic agent for the treatment of human cervical cancer.

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Section: Discussionsupporting

confidence: 72%

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

Lin

Lee

Chen

et al. 2018

Cell Physiol Biochem

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“…Li et al (2017) showed that silibinin induced apoptosis in gastric cancer BGC823 cells [ 32 ]. Silibinin induced apoptosis in human choriocarcinoma cells [ 33 ]. The anti-cancer effects of SLM and silibinin on salivary gland cancer have also been reported by Choi et al (2017) [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Silymarin-Loaded Nanoparticles on HT-29 Human Colon Cancer Cells

et al. 2018

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Background and objective: Previous studies have demonstrated the anti-cancer effects of silymarin (SLM). However, the low bioavailability of SLM has restricted its use. This study investigated the toxic effect of nanostructured SLM encapsulated in micelles (Nano-SLM) on the growth of the HT-29 human colon cancer cell line. Materials and methods: HT-29 cells were treated with 25 μM/mL of SLM or Nano-SLM for 48 h. MTT and colony formation assays were used to assess the cytotoxicity and proliferation of HT-29 cells, respectively. The cells were stained with annexin V/PI for assessment of apoptosis. Results: MTT assays revealed that Nano-SLM treatment was able to exert a more pronounced toxic effect on the HT-29 cells as compared to free SLM treatment (p < 0.01). In the Nano-SLM-treated cells, colony numbers were significantly reduced in comparison to the free SLM-treated cells (p < 0.01). Apoptotic and necrotic indexes of Nano-SLM-treated HT-29 cells were also significantly increased in comparison to those of the free SLM-treated cells (p < 0.01). The viability, proliferation and apoptosis of healthy cells (NIH-3T3 cells) were not changed in response to Nano-SLM or SLM. Conclusions: Our results indicate that Nano-SLM enhances the anti-cancer effects of SLM against human colon cancer cells.

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“…Silibinin, the most famous and active compound isolated from Silybum marianum (milk thistle) traditionally used to protect from liver injury, could induce apoptosis related to mitochondrial Ca 2+ influx in C. albicans cells [ 84 , 85 ]. Silibinin could alleviate mitochondrial dysfunction in mice model of cisplatin-induced acute kidney injury through Sirt3 activation, although in vitro proapoptotic effects through inducing ROS production have been also reported [ 86 , 87 ]. The safe profile with silibinin, evidenced by marketed health food and clinical trials, makes silibinin a very promising candidate for antifungal therapies against Candida infections although there is still a long way to go [ 88 ].…”

Section: Compounds Targeting Mitochondriamentioning

confidence: 99%

Antifungal Compounds againstCandidaInfections from Traditional Chinese Medicine

Liu

Zhang

et al. 2017

BioMed Research International

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Infections caused by Candida albicans, often refractory and with high morbidity and mortality, cause a heavy burden on the public health while the current antifungal drugs are limited and are associated with toxicity and resistance. Many plant-derived molecules including compounds isolated from traditional Chinese medicine (TCM) are reported to have antifungal activity through different targets such as cell membrane, cell wall, mitochondria, and virulence factors. Here, we review the recent progress in the anti-Candida compounds from TCM, as well as their antifungal mechanisms. Considering the diverse targets and structures, compounds from TCM might be a potential library for antifungal drug development.

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Silibinin stimluates apoptosis by inducing generation of ROS and ER stress in human choriocarcinoma cells

Cited by 28 publications

References 37 publications

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

Effects of Silymarin-Loaded Nanoparticles on HT-29 Human Colon Cancer Cells

Antifungal Compounds againstCandidaInfections from Traditional Chinese Medicine

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