Icariside II-induced mitochondrion and lysosome mediated apoptosis is counterbalanced by an autophagic salvage response in hepatoblastoma

Geng, Yadi; Zhang, Chao; Yamin, Shi; Xia, Yuan‐Zheng; Guo, Chao; Yang, Lei; Kong, Ling–Yi

doi:10.1016/j.canlet.2015.05.032

Cited by 30 publications

(20 citation statements)

References 63 publications

(84 reference statements)

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“…JNK siRNA [ 56 ], LC3B siRNA [ 57 ], p21 siRNA pools (siRNA1: CAGGCGGUUAUGAAAUUCAdTdT, siRNA2: GAUGGAACUUCGACUUUGUdTdT and siRNA3: CCUCUGGCAUUAGAAUUAUdTdT) and non-targeting siRNA were synthesized by Biomics (Nantong, China). For siRNA transfection, MDA-MB-231 cells were seeded in 6-well plates or glass-bottom dishes (1 × 10 6 cells per well).…”

Section: Methodsmentioning

confidence: 99%

Anti-proliferation of triple-negative breast cancer cells with physagulide P: ROS/JNK signaling pathway induces apoptosis and autophagic cell death

Zhang

Gao

et al. 2017

Oncotarget

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Physagulide P (PP), a new natural compound, was isolated from Physalis angulate L. in our laboratory. In this study, we demonstrated that PP potently suppressed cell proliferation by inducing G2/M phase arrest in MDA-MB-231 and MDA-MB-468 cells. Moreover, PP provoked apoptosis by decreasing the mitochondrial membrane potential and elevating the Bax/Bcl-2 protein expression ratio. The caspase inhibitor Z-VAD-FMK partly restore cell viability, suggesting that apoptosis plays as an important role in the anti-proliferative effect of PP. PP-treated cells also underwent autophagy, as evidenced by the formation of autophagosomes and the accumulation of LC3BII. Furthermore, the knockdown of LC3B reduced PP-induced cytotoxicity, indicating that autophagy played an anticancer effect. PP also induced the generation of reactive oxygen species (ROS) and resulted in c-Jun N-terminal kinases (JNK) activation. Accordingly, JNK siRNA significantly attenuated PP-triggered apoptosis and autophagy, and ROS scavengers almost completely reverse this apoptosis and autophagy. The ROS scavenger also blocked PP-induced G2/M phase arrest and the phosphorylation of JNK. Our results revealed that PP induced G2/M phase arrest, apoptosis and autophagy via the ROS/JNK signaling pathway in MDA-MB-231 and MDA-MB-468 cells. Therefore, PP is a promising candidate for the development of antitumor drugs for the treatment of triple-negative breast cancer.

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Section: Methodsmentioning

confidence: 99%

Anti-proliferation of triple-negative breast cancer cells with physagulide P: ROS/JNK signaling pathway induces apoptosis and autophagic cell death

Zhang

Gao

et al. 2017

Oncotarget

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“…Arief et al (2015) proved that IS has cytotoxic and cytostatic effects on six cancer cell lines. Geng et al (2015) investigated the underlying mechanism of IS against hepatoblastoma cells in vitro and in vivo, and discovered that it can decrease the viability of HepG2 cells in a time-and concentrationdependent manner and inhibit tumor growth in mice transplanted with H22 liver carcinomas. Thus, as a promising chemotherapeutic agent, IS plays multiple roles in inducing mitochondrial and lysosomal damage that leads to cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Preparation and evaluation of icariside II-loaded binary mixed micelles using Solutol HS15 and Pluronic F127 as carriers

et al. 2016

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An effective anti-cancer drug, icariside II (IS), has been used to treat a variety of cancers in vitro. However, its poor aqueous solubility and permeability lead to low oral bioavailability. The aim of this work was to use Solutol Õ HS15 and Pluronic F127 as surfactants to develop novel mixed micelles to enhance the oral bioavailability of IS by improving permeability and inhibiting efflux. The IS-loaded mixed micelles were prepared using the method of ethanol thin-film hydration. The physicochemical properties, dissolution property, oral bioavailability of the male SD rats, permeability and efflux of Caco-2 transport models, and gastrointestinal safety of the mixed micelles were evaluated. The optimized IS-loaded mixed micelles showed that at 4:1 ratio of Solutol Õ HS15 and Pluronic F127, the particle size was 12.88 nm with an acceptable polydispersity index of 0.172. Entrapment efficiency (94.6%) and drug loading (9.7%) contributed to the high solubility (11.7 mg/mL in water) of IS, which increased about 900-fold. The SF-IS mixed micelle release profile showed a better sustained release property than that of IS. In Caco-2 cell monolayer models, the efflux ratio dramatically decreased by 83.5%, and the relative bioavailability of the mixed micelles (AUC 0-1 ) compared with that of IS (AUC 0-1 ) was 317%, indicating potential for clinical application. In addition, a gastrointestinal safety assay also provided reliable clinical evidence for the safe use of this micelle.

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“…The main bioactive compounds isolated from Herbal Epimedii include icariin, icaritin, icariside I and icariside II with similar molecular structure. Recently, a large number of studies have focused on the anti-cancer activity of three compounds including icariin [37], icaritin [38], and icariside II [39] in a variety of cancers, such as hepatocellular cancer [29], prostatic cancer [38], and multiple myeloma [40]. Less work, however, have been done on the antitumor activity of icariside I probably due to its too low content in Epimedium.…”

Section: Discussionmentioning

confidence: 99%

Immunological Anti-Tumor Activity of Icariside I by Regulating Gut Microbiota and Its Derived Metabolites in a Melanoma Mouse Model

Chen

Cao

Shi

et al. 2020

Preprint

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Background Emerging evidence has shown that gut microbiome plays important roles in antitumor immunotherapy by shaping systemic immune responses. Specifically, Lactobacillus spp. and Bifidobacterium spp. were previously reported to enhance host immunity and inhibit tumor growth. Furthermore, microbiota-derived metabolites such as short-chain fatty acids (SCFAs) and indole derivatives are gradually regarded as immunomodulatory molecules involved in metabolic signaling pathways. Methods A B16F10 melanoma model was selected as a tumor-bearing animal for the investigation of immunological anti-tumor activity of Icariside I. Gut microbiota structure and composition in cecal content of mice was firstly analyzed by 16S rRNA gene sequence with the goal of screening those bacteria highly associated with tumor immunotherapy. Subsequently, targeted metabolomics approach was employed to quantitatively determine microbiota-derived metabolites such as SCFAs and indole derivatives. The population of multiple lymphocyte subsets in peripheral blood were measured with flowcytometry to evaluate changes of host immunity. Results Icariside I significantly inhibited B16F10 melanoma growth in vivo through regulation of gut microbiota and host immune. Oral administration of icariside I improved the altered gut microbiota community with marked restoration of Lactobacillus spp. and Bifidobacterium spp. abundance. Icariside I was also able to improve the levels of microbiota-derived metabolites such as short-chain fatty acids (SCFAs) and indole derivatives, consequently repairing intestinal barrier and systemic inflammation of tumor-bearing mice. Furthermore, icariside I up-regulated multiple lymphocyte subsets including CD4 + and CD8 + T cells or NK and NKT cells in peripheral blood. Conclusions These results suggested that icariside I may be developed as a novel and natural anticancer adjuvant via microbiome remodeling and host immune regulation.

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Icariside II-induced mitochondrion and lysosome mediated apoptosis is counterbalanced by an autophagic salvage response in hepatoblastoma

Cited by 30 publications

References 63 publications

Anti-proliferation of triple-negative breast cancer cells with physagulide P: ROS/JNK signaling pathway induces apoptosis and autophagic cell death

Anti-proliferation of triple-negative breast cancer cells with physagulide P: ROS/JNK signaling pathway induces apoptosis and autophagic cell death

Preparation and evaluation of icariside II-loaded binary mixed micelles using Solutol HS15 and Pluronic F127 as carriers

Immunological Anti-Tumor Activity of Icariside I by Regulating Gut Microbiota and Its Derived Metabolites in a Melanoma Mouse Model

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