Chrysin induces cell apoptosis via activation of the p53/Bcl-2/caspase-9 pathway in hepatocellular carcinoma cells

Zhang, Qingyu; Ma, Shenglin; Liu, Bin; Liu, Jie; Zhu, Runzhi; Li, Mingyi

doi:10.3892/etm.2016.3282

Cited by 53 publications

(38 citation statements)

References 24 publications

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“…14,16,32 In the present study, chrysinNPs were observed to have anticancer effects in A549-derived tumor tissues. In fact, chrysin-NPs inhibited cell proliferation and induced apoptosis in tumor tissues ( Figure 6).…”

Section: Discussionmentioning

confidence: 87%

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Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Kim¹,

Lim

Shim³

et al. 2017

IJN

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Chrysin is a flavone that is found in several plants and in honeycomb and possesses various biological activities. However, its low solubility means it has poor bioavailability, which must be resolved to enable its pharmaceutical applications. In the present study, chrysin was incorporated into methoxy poly(ethylene glycol)-β-polycaprolactone nanoparticles (chrysin-NPs) using the oil-in-water technique in order to overcome problems associated with chrysin. The properties of chrysin-NPs were analyzed, and their anticancer effects were investigated in vitro and in vivo. Chrysin-NPs were 77 nm sized (as determined by dynamic laser light scattering) and showed a monodisperse distribution. The zeta potential of chrysin-NPs was −2.22 mV, and they were spherically shaped by cryo-transmission electron microscopy (cryo-TEM). The loading efficiency of chrysin-NPs was 46.96%. Chrysin-NPs retained the cytotoxicity of chrysin in A549 cells. The therapeutic efficacies of chrysin-NPs were compared with those of chrysin in an A549-derived xenograft mouse model. Chrysin-NPs were intravenously injected at a 10 times lower dosage than chrysin 3 times per week (q2d×3/week). However, free chrysin was orally administrated 5 times per week (q1d×5/week). Chrysin-NP-treated group showed significant tumor growth delay, which was similar to that of chrysin-treated group, despite the considerably lower total dosage. These results suggest that the injectable chrysin-NPs enhance therapeutic efficacy in vivo and offer a beneficial formulation for chemotherapy.

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Section: Discussionmentioning

confidence: 87%

“…Chrysin is a natural active component found in various herbs, mushroom, and propolis 2 and has anti-inflammatory, 3,4 antiaging, 5 antiviral, 6 antioxidant, [7][8][9] antidiabetes, 10 antiaromatase, 11,12 and anticancer [13][14][15][16] activities. Accordingly, it is widely held that chrysin has potential pharmaceutical applications.…”

Section: Introductionmentioning

confidence: 99%

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Kim¹,

Lim

Shim³

et al. 2017

IJN

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“…Specifically, chrysin suppresses development and progression of cancer cells originating from prostate, skin, colon, breast, liver, and lung (Kasala et al, ). Chrysin induces apoptosis by stimulating pro‐apototic proteins and cleavage of caspases in hepatocellular carcinoma cells (Zhang et al, ). Chrysin inhibits hypoxia‐induced survival of breast cancer cells by inactivating hypoxia‐induced STAT3 phosphorylation and reducing VEGF expression to control metastatic progression and tumor growth (Lirdprapamongkol et al, ).…”

Section: Introductionmentioning

confidence: 99%

Chrysin induces death of prostate cancer cells by inducing ROS and ER stress

Ryu

Lim

Bazer

et al. 2017

Journal Cellular Physiology

115

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Chrysin is a natural flavone found in numerous plant extracts, honey, and propolis that has multiple biological activities including anti-cancer effects. Understanding of biological mechanisms mediated in response to chrysin in cancerous cells may provide novel insight into chemotherapeutic approaches with reduced side effects in cancers. In the present study, we investigated functional roles of chrysin in progression of prostate cancer cells using DU145 and PC-3 cell lines. The results showed that chrysin induced apoptosis of cells evidenced by DNA fragmentation and increasing the population of both DU145 and PC-3 cells in the sub-G phase of the cell cycle. In addition, chrysin reduced expression of proliferating cell nuclear antigen in the prostate cancer cell lines compared to untreated prostate cancer cells. Moreover, chrysin induced loss of mitochondria membrane potential (MMP), while increasing production of reactive oxygen species (ROS) and lipid peroxidation in a dose-dependent manner. Also, it induced endoplasmic reticulum (ER) stress through activation of unfolded protein response (UPR) proteins including PRKR-like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), and 78 kDa glucose-regulated protein (GRP78) in DU145 and PC-3 cells. The chrysin-mediated intracellular signaling pathways suppressed phosphoinositide 3-kinase (PI3K) and the abundance of AKT, P70S6K, S6, and P90RSK proteins, but stimulated mitogen-activated protein kinases (MAPK) and activation of ERK1/2 and P38 proteins in the prostate cancer cells. Collectively, these results indicate that chrysin initiates cell death through induction of mitochondrial-mediated apoptosis and ER stress, and regulation of signaling pathways responsible for proliferation of prostate cancer cells.

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“…The presence of HP53 mutation in the plasma could be indicative of HCC nodules [16]. Zhang et al have suggested that chrysin (natural flavonoid) may promoted HCC cell apoptosis via activation of the p53/Bcl2/caspase-9 apoptotic signalling pathway [17].…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory cytokines (IL-6, IL-18) and apoptotic factors (HP 53, survivin) in patients with alcoholic liver cirrhosis

Prystupa¹,

Kiciński²,

Sak³

et al. 2017

J Pre Clin Clin Res.

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and apoptotic factors (HP 53, survivin) in patients with alcoholic liver cirrhosis. J Pre-Clin Clin Res. 2017;11(1):1-5. doi: 10.26444/ jpccr/75134 AbstractBackground. Apoptosis is involved in the pathogenesis of alcoholic liver cirrhosis. Its development can be triggered by an inflammatory process. In the present study, levels of apoptotic factors -survivin human protein p53 (HP 53) and IL-6, IL-18 were determined according to the stage of liver cirrhosis. Material and methods. Seventy patients with alcoholic liver cirrhosis, treated in various hospitals of the Lublin region, Poland were included in the study. Serum levels of IL-6, IL-18, HP53 and survivin were determined by the enzyme-linked immunosorbent assay (ELISA) technique. Results. The serum level of survivin in patients with alcoholic liver cirrhosis was not statistically different from that found in the control group. The level of HP53 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (16.53±22.69 vs. 0.39±1.31 U/ml; p<0.001). Likewise, the level of IL-6 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (33.83±41.78 vs. 0.88 ± 0.56 pg/ml; p<0.001). Moreover, the level of IL-18 was significantly higher in the group of patients with liver cirrhosis compared to the control group (23.96±31.07 vs. 5.3±8.6 pg/ml; p<0.001). Conclusion. In conclusion, increased serum levels of IL-6 and IL-18 were demonstrated in patients with alcoholic liver cirrhosis. Moreover, the liver cirrhosis patients had elevated levels of HP53, which is a marker of apoptosis. Our results did not demonstrate the correlation between the levels of apoptosis markers (survivin, HP53) and the levels of cytokines (IL-6, IL-18) in the blood serum.

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Chrysin induces cell apoptosis via activation of the p53/Bcl-2/caspase-9 pathway in hepatocellular carcinoma cells

Cited by 53 publications

References 24 publications

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

Chrysin induces death of prostate cancer cells by inducing ROS and ER stress

Proinflammatory cytokines (IL-6, IL-18) and apoptotic factors (HP 53, survivin) in patients with alcoholic liver cirrhosis

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