Induction of Apoptosis by Icariside II through Extrinsic and Intrinsic Signaling Pathways in Human Breast Cancer MCF7 Cells

Huang, Chaoqing; Chen, Xiaoguang; Guo, Baolin; Huang, Wenhua; Shen, Ting; Sun, Xinguang; Xiao, Pei‐Gen; Zhou, Qing

doi:10.1271/bbb.120077

Cited by 31 publications

(31 citation statements)

References 47 publications

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“…In previous studies, IS showed cytotoxic effects in several cultured cell lines through activation of caspase cascades by mitochondrial dysfunction [26][27][28]. Similarly, our data demonstrated that IS treatment induced signs of MMP including mitochondrial mass accumulation, reactive oxygen species formation and decreased ΔΨm.…”

Section: Discussionsupporting

confidence: 83%

“…1B). Previous studies indicate that IS impairs mitochondria via triggering MMP in different cancer cells [26][27][28]. Therefore, we tested whether IS induced MMP in HepG2 cells.…”

Section: Is Induces Mitochondrial Dysfunction In Human Hepatoblastomamentioning

confidence: 97%

“…Icariside II (IS) is a flavonoid from Herba Epimedium koreanum Nakai (Berberidaceae) that has demonstrated a great potential as a novel anticancer agent for several types of cancers [23][24][25]. Previous studies show that IS treatment induces mitochondrial malfunction and apoptosis [26][27][28]. However, the events of lysosomes and autophagy as well as their roles in IS-induced cell death have never been investigated before and need further clarification.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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Section: Discussionsupporting

confidence: 83%

“…1B). Previous studies indicate that IS impairs mitochondria via triggering MMP in different cancer cells [26][27][28]. Therefore, we tested whether IS induced MMP in HepG2 cells.…”

Section: Is Induces Mitochondrial Dysfunction In Human Hepatoblastomamentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2015

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“…For example, several studies have confirmed the pro-survival function of icariside II [13, 14]. Others, however, showed that icariside II may induce apoptosis in number of cancer cells [12, 15–17]. Whether icariside II could protect Dex- induced osteoblast cell damages has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone

Liu

Feng

et al. 2016

Oncotarget

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The potential effect of icariside II on dexamethasone-induced osteoblast cell damages was evaluated here. In MC3T3-E1 osteoblastic cells and the primary murine osteoblasts, co-treatment with icariside II dramatically attenuated dexamethasone- induced cell death and apoptosis. Icariside II activated Akt signaling, which is required for its actions in osteoblasts. Akt inhibitors (LY294002, perifosine and MK-2206) almost abolished icariside II-induced osteoblast cytoprotection against dexamethasone. Further studies showed that icariside II activated Nrf2 signaling, downstream of Akt, to inhibit dexamethasone-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary osteoblasts. On the other hand, Nrf2 shRNA knockdown inhibited icariside II-induced anti-dexamethasone cytoprotection in MC3T3-E1 cells. Finally, we showed that icariside II induced heparin-binding EGF (HB-EGF) production and EGFR trans-activation in MC3T3-E1 cells. EGFR inhibition, via anti-HB-EGF antibody, EGFR inhibitor AG1478 or EGFR shRNA knockdown, almost blocked icariside II-induced Akt-Nrf2 activation in MC3T3-E1 cells. Collectively, we conclude that icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone. Icariside II might have translational value for the treatment of dexamethasone-associated osteoporosis/osteonecrosis.

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“…Consistent with these features of apoptosis, VK4-treated U2OS cells exhibited cell shrinkage and cleavage of caspase-3. Apoptosis can be divided into the following three major categories: i) Mitochondrial caspase-dependent apoptosis or intrinsic apoptosis; ii) extrinsic apoptosis; and iii) caspase-independent apoptosis (23,24). In order to gain further insight into the molecular mechanisms underlying VK4-induced apoptosis, annexin V/PI staining of VK4-treated U2OS cells exposed to a pan-caspase inhibitor Z-VAD-FMK was performed.…”

Section: Discussionmentioning

confidence: 99%

Vitamin K4 inhibits the proliferation and induces apoptosis of U2OS osteosarcoma cells via mitochondrial dysfunction

Khan

Gao

et al. 2016

Molecular Medicine Reports

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Vitamin K (VK) is a group of fat‑soluble vitamins, which serve important roles in blood coagulation and bone metabolism. A recent study reported that several VK subtypes possess antitumor properties, however the antitumor effects of VK in osteosarcoma are unknown. The present study aimed to identify the antitumor effects of VK in osteosarcoma and the possible underlying mechanism of action. The effect of VK4 on cell viability was determined using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. Cellular and nuclear morphological changes were observed by phase contrast microscopy. Cell cycle analysis, apoptotic rate, mitochondrial membrane potential and levels of reactive oxygen species (ROS) were detected by flow cytometry. In vitro cancer cell migration activities were evaluated using a Wound healing assay and Transwell microplates. The results demonstrated that VK4 arrested the cells in S phase and induced apoptosis. Additional mechanistic studies indicated that the induction of apoptosis by VK4 was associated with the increased production of reactive oxygen species, dissipation of the mitochondrial membrane potential, decreased Bcl‑2 family protein expression levels and activation of caspase‑3. In conclusion, the results suggest that the sensitivity of U2OS osteosarcoma cells to VK4 may be as a result of mitochondrial dysfunction. As it is readily available for human consumption, VK4 may therefore present a novel therapeutic candidate for the treatment of patients with osteosarcoma.

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Induction of Apoptosis by Icariside II through Extrinsic and Intrinsic Signaling Pathways in Human Breast Cancer MCF7 Cells

Cited by 31 publications

References 47 publications

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

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

Icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone

Vitamin K4 inhibits the proliferation and induces apoptosis of U2OS osteosarcoma cells via mitochondrial dysfunction

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