hypocrellin-b and Liver-Neoplasms

Hepatocellular carcinoma (HCC) is an inflammation-induced and chemotherapy-resistant common liver cancer, and a major cause of death. Some natural products have been found to be used as photosensitizers in photodynamic therapy of HCC. Due to its specific molecular structure diversities and biological activities, current status of HCC treatment with nature production remains unsatisfactory, owing largely to the toxicity, side effect and inefficiency to drug targeting. Herein, we show a nanoparticle-based broad-spectrum anti-inflammatory strategy that naïve neutrophil membrane-coated PLGA nanoparticles (NM-HB NPs) were constructed for synchronous nearinfrared fluorescence (NIR FL) imaging and photodynamic therapy (PDT) for HCC. Moreover, NM-HB NPs inhibited the expression of JUNB and promoted the ROS production. JUNB depletion enhanced the anti-HCC effect of NM-HB NPs. Importantly, it was shown that NM-HB NPs are well targeted to the tumor site and overcomes the blood circulation and immune elimination in vivo and vitro. In a mouse model of HCC, the neutrophil membrane-coated nanoparticles (NM-HB NPs) show significant therapeutic efficacy by PDT and suppressing tumor tissue increase. All results demonstrated that NM coated HB NPs representing a viable and effective treatment option for HCC.

Topics: Animals; Apoptosis; Carcinoma, Hepatocellular; Cell Line; Cell Membrane; Humans; Interleukin-6; Liver Neoplasms; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Neutrophils; Nuclear Export Signals; Perylene; Photochemotherapy; Quinones; Rats; Reactive Oxygen Species; Transcription Factors; Tumor Burden; Tumor Necrosis Factor-alpha

To study subcellular localization of hypocrellin B in hepatocellular carcinoma cells, and hypocrellin B-mediated sonodynamic action-induced cell damage.. After incubation with 2.5 μM of hypocrellin B, human hepatocellular carcinoma HepG2 cells were exposed to ultrasound waves for 8 sec at an intensity of 0.46 W/cm(2). Clonogenic survival of HepG2 cells was measured using a colony forming assay and light microscope. Ultrastructural morphology was observed using transmission electron microscope (TEM) and mitochondrial membrane potential (MMP) was assessed using confocal laser scanning microcope (CLSM) after rhodamine 123 staining. Additionally, subcellular localization of hypocrellin B in HepG2 cells with organelle probe staining was also observed using CLSM.. The colony forming units of HepG2 cells decreased substantially after sonodynamic treatment. The results of TEM showed microvilli disappearance, apoptotic body formation, swollen mitochondria with loss of cristae and mitochondrial myelin-like features (or membrane whorls). Collapse of MMP was found in the treated cells. Hypocrellin B was distributed in mitochondria and lysosomes as well as in endoplasmic reticulum and Golgi apparatus.. The findings demonstrated that sonodynamic action of hypocrellin B induced mitochondrial damage, survival inhibition, and apoptosis of HepG2 cells. Additionally, other subcellular organelles such as endoplasmic reticulum, Golgi apparatus and lysosomes were also the targets of hypocrellin B-mediated sonodynamic action as well as mitochondria.

Topics: Carcinoma, Hepatocellular; Cell Survival; Hep G2 Cells; Humans; Intracellular Space; Liver Neoplasms; Membrane Potential, Mitochondrial; Perylene; Protein Transport; Quinones; Ultrasonic Therapy

The present study aims to investigate apoptosis of hepatocellular carcinoma cells induced by hypocrellin B-mediated sonodynamic action.. The hypocrellin B concentration was kept constant at 2.5 μM and cells from the hepatocellular carcinoma HepG2 cell line were exposed to ultrasound with an intensity of 0.46 W/cm(2) for 8s. Cell cytotoxicity was quantified using an MTT assay 24 h after sonodynamic therapy (SDT) of hypocrellin B. Apoptosis was investigated using a flow cytometry with Annexin V-FITC and propidium iodine staining. Intracellular reactive oxygen species (ROS) levels were detected using a flow cytometry with 2,7-dichlorodihydrofluorecein diacetate (DCFH-DA) staining.. The cytotoxicity of hypocrellin B-mediated sonodynamic action on HepG2 cells was significantly higher than those of other treatments including ultrasound alone, hypocrellin B alone and sham treatment. Flow cytometry showed that hypocrellin B-induced sonodynamic action markedly enhanced the apoptotic rate of HepG2 cells. Increased ROS was observed in HepG2 cells after being treated with hypocrellin B-mediated sonodynamic action.. Our data demonstrated that hypocrellin B-mediated sonodynamic action remarkably induced apoptosis of HepG2 cells, suggesting that apoptosis is an important mechanism of cell death induced by hypocrellin B-mediated SDT.

Topics: Analysis of Variance; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Flow Cytometry; Humans; Liver Neoplasms; Perylene; Photosensitizing Agents; Quinones; Reactive Oxygen Species; Staining and Labeling; Ultrasonic Therapy