Anti-liver Cancer Research Articles

Hyaluronidase-trigger nanocarriers for targeted delivery of anti-liver cancer compound.

Chemotherapy is recognized as one of the significant treatment methods for liver cancer. The compound celastrol (CSL) could effectively inhibit the proliferation, migration, and invasion of liver cancer cells, which is regarded as a promising candidate to become a mainstream anti-liver cancer drug. However, the application of CSL in liver cancer chemotherapy is limited due to its systemic toxicity, poor water solubility, multidrug resistance, premature degradation, and lack of tumor targeting. Meanwhile, in order to comply with the current concept of precision medicine, precisely targeted delivery of the anti-liver compound CSL was desired. This paper takes into account that liver cancer cells were equipped with hyaluronic acid (HA) receptors (CD44) on their surface and overexpressed. Hyaluronidase (HAase) capable of degrading HA, HAase-responsive nanocarriers (NCs), named HA/(MI)7-β-CD NCs, were prepared based on the electrostatic interaction between HA and imidazole moieties modified β-cyclodextrin (MI)7-β-CD. HA/(MI)7-β-CD NCs showed disassembly properties under HAase stimuli, which was utilized to trap, deliver, and the controllable release of the anti-liver cancer compound CSL. Furthermore, cytotoxicity assay experiments revealed that CSL-trapped HA/(MI)7-β-CD NCs not only reduced cytotoxicity for normal cells but also effectively inhibited the survival for five tumor cells, and even the apoptotic effect of CSL-trapped NCs with a concentration of 5 μg mL-1 on tumor cells (SMMC-7721) was consistent with free CSL. Cell uptake experiments demonstrated HA/(MI)7-β-CD NCs possessed the capability of targeted drug delivery to cancerous cells. HA/(MI)7-β-CD NCs exhibited site-specific and controllable release performance, which is anticipated to proceed further in precision-targeted drug delivery systems.

Nitric oxide/paclitaxel micelles enhance anti-liver cancer effects and paclitaxel sensitivity by inducing ferroptosis, endoplasmic reticulum stress and pyroptosis.

The objective of this study was to investigate the anticancer activities of biodegradable polymeric micelles composed of monomethoxy poly(ethylene glycol), polylactic acid, and nitric oxide (mPEG-PLA-NO) loaded with paclitaxel (PTX) as a nanomedicine delivery system. We aimed to compare the anticancer effects of these NO/PTX micelles with PTX alone and elucidate their mechanism of action. We evaluated the impact of NO/PTX and PTX on cell viability using Cell Counting Kit-8 (CCK8) assays conducted on the Bel-7402 liver cancer cell line. Additionally, we employed H22 xenografted mice to assess the in vivo tumor growth inhibitory activity of NO/PTX. To examine the cytotoxicity of NO/PTX, the intracellular levels of reactive oxygen species (ROS), and the expression of ferroptosis-related proteins, we conducted experiments in the presence of the ferroptosis inhibitor ferrostatin-1 (Fer-1) or the ROS inhibitor N-acetyl cysteine (NAC). Furthermore, we investigated the expression of endoplasmic reticulum stress (ERS) and apoptosis-associated proteins. Our results demonstrated that NO/PTX exhibited enhanced anticancer effects compared to PTX alone in both Bel-7402 cells and H22 xenografted mice. The addition of Fer-1 or NAC reduced the anticancer activity of NO/PTX, indicating the involvement of ferroptosis and ROS in its mechanism of action. Furthermore, NO/PTX modulated the expression of proteins related to ERS and apoptosis, indicating the activation of these cellular pathways. The anticancer effects of NO/PTX in liver cancer cells were mediated through the induction of ferroptosis, pyroptosis, ERS, and apoptosis-associated networks. Ferroptosis and pyroptosis were activated by treatment of NO/PTX at low concentration, whereas ERS was induced to trigger apoptosis at high concentration. The superior anti-tumor effect of NO/PTX may be attributed to the downregulation of a multidrug resistance transporter and the sensitization of cells to PTX chemotherapy. In summary, our study highlights the potential of mPEG-PLA-NO micelles loaded with PTX as a nanomedicine delivery system for liver cancer treatment. The observed enhancement in anticancer activity, combined with the modulation of key cellular pathways, provides valuable insights into the therapeutic potential of NO/PTX in overcoming resistance and improving treatment outcomes in liver cancer patients.

Rose and eucalyptus essential oil as potent anti-liver cancer agents

Rose and eucalyptus essential oil as potent anti-liver cancer agents

Curcumae Rhizoma - combined with Sparganii Rhizoma in the treatment of liver cancer: Chemical analysis using UPLC-LTQ-Orbitrap MSn, network analysis, and experimental assessment.

Objective: Curcumae Rhizoma-Sparganii Rhizoma (CR-SR) is a traditional botanical drug pair that can promote blood circulation, remove blood stasis, and treat tumors in clinics. The aim of the present study was to investigate the therapeutic material basis and potential mechanisms of CR-SR, CR, and SR for the treatment of liver cancer. Method: The chemical profile analyses of CR-SR, CR, and SR were performed by molecular networking and UPLC-LTQ-Orbitrap MSn. The anti-liver cancer activities of CR-SR, CR, and SR were assessed by using a zebrafish xenograft model in vivo for the first time and detected by the HepG2 cell model in vitro. Combining the network analysis and molecular docking, real-time quantitative polymerase chain reaction (RT-qPCR) experiments were undertaken to further explore the mechanisms of CR-SR, CR, and SR for the treatment of liver cancer. Results: In total, 65 components were identified in CR-SR, CR, and SR. Based on the clusters of molecular networking, a total of 12 novel diarylheptanoids were identified from CR-SR and CR. By combining our results with information from the literature, 32 sesquiterpenoids and 21 cyclic dipeptides were identified from CR-SR, CR, and SR. The anti-liver cancer activities were observed in both the drug pair and the single botanical drugs in vitro and in vivo, and the order of activity was CR-SR > CR > SR. They could downregulate the expression of proto-oncogene tyrosine-protein kinase Src (SRC), epidermal growth factor receptor (EGFR), estrogen receptor-α (ESR1), prostaglandin endoperoxide synthase 2 (PTGS2), and amyloid precursor protein (APP). Conclusion: Taken together, the present study provided an experimental basis for the therapeutic material basis and potential molecular mechanisms of CR-SR, CR, and SR. This study provided a novel insight for objective clinical treatment of liver cancer.

Pharmacokinetic characteristics of emodin in polygoni Multiflori Radix Praeparata

Ethnopharmacological relevancePolygoni Multiflori Radix Praeparata (Zhiheshouwu) has been a Wudang Taoist medicine for tonifying the liver and kidney, resolving turbidity and reducing lipid. Emodin is one of the active anthraquinones in Zhiheshouwu. Our previous studies showed that emodin (EM) and the other anthraquinones in Zhiheshouwu extract (HSWE) exerted similar inhibitory effects on liver cancer cells in vitro. However, it is still unknown if the other anthraquinones enhance pharmacokinetics (PK) of EM in HSWE in vivo. Aim of the studyIn this study, we compared the PK characteristics of EM alone with that in Zhiheshouwu aiming to explore which anthraquinones in HSWE contribute to the changed PK of EM in rats. Materials and methodsQuality control of HSWE was determined using high performance liquid chromatography (HPLC). The ratios of emodin to other anthraquinones, physcion (PH), chrysophanol (CH), rhein (RH), aloe-emodin (AE), emodin-8-O-β-D-glycoside (EMG), physcion-1-O-β-D-glycoside (PHG) and chrysophanol-8-O-β-D-glycoside (CHG) in HSWE were determined and analyzed using UPLC combined with tandem mass spectrometry (UPLC/MS). The PK parameters and intestinal tissue concentration of EM alone, EM in HSWE, or with other anthraquinones in SD rats were analyzed using UPLC/MS. ResultsThe quality of the Zhiheshouwu samples met the quality standard of the Chinese Pharmacopoeia (Version 2020). The PK results showed that compared with EM alone, Cmax (239.90 ± 146.71 vs. 898.46 ± 291.62, P < 0.001), Tmax (0.26 ± 0.15 vs. 12.55 ± 1.33, P < 0.001), AUC0-t (1575.09 ± 570.46 vs. 12154.96 ± 5394.25, P < 0.001), and AUC0-∞ (4742.51 ± 1837.62 vs. 37131.34 ± 21647.39, P < 0.001) of EM in HSWE were decreased due to PH and EMG, while the values of Vd (380.75 ± 217.74 vs. 11.75 ± 7.35, P < 0.001), T1/2 (10.81 ± 1.99 vs. 6.65 ± 2.76, P < 0.05) and CL (19.30 ± 7.82 vs. 2.78 ± 1.88, P < 0.001) of EM in HSWE were increased due to PH and AE. In addition, the intestinal tissue concentration of emodin in HSWE was decreased compared with that of EM alone in 20 and 780 min (25.37 ± 5.98 vs. 43.29 ± 4.16 and 26.72 ± 4.03 vs. 43.40 ± 14.19, respectively. P < 0.05) dominantly due to RH and PH. ConclusionIn conclusion, compared with treatment of EM alone, the AUC0-t value of EM in HSWE was decreased with different ways in rats. PH shortened Tmax, and increased Vd and CL. While AE prolonged T1/2 of EM. This indicated that the other anthraquinones in HSWE changed the PK of EM in rats and participated in the complex effects of EM on liver cancer. Besides the other anthraquinones, other components (e.g., 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside) in Zhiheshouwu may contribute in the pharmacokinetic and pharmacodynamic interactions with EM for anti-liver cancer.

Laminaria japonica Peptides Suppress Liver Cancer by Inducing Apoptosis: Possible Signaling Pathways and Mechanism.

The anticancer properties of Laminaria japonica peptides (LJPs) have never been studied. Here, we extracted LJPs from fresh seaweed and explored their anti-liver cancer activity (in vivo and in vitro). LJPs were isolated/purified by HPLC-ESI-MS. HepG2 cell apoptosis and cell cycle were evaluated. MTT assays were used to examine the cytotoxicity of LJPs. Caspase activation of caspases 3 and 9, cleaved caspases 3 and 9, and cleaved PARP was examined by Western blotting. The PI3K/AKT pathway and the phosphorylation states of MAPKs (p38 and JNK) were examined. We found that the LJP-1 peptide had the most antiproliferative activity in H22 cells in vitro. LJP-1 blocked H22 cells in the G0/G1 phase, accompanied by inhibition of cyclin expression. LJP-1 induced apoptosis through caspase activation and regulation of the ASK1/MAPK pathway. Concurrent in vivo studies demonstrated that LJP-1 significantly inhibited tumor growth and induced tumor cell apoptosis/necrosis. In conclusion, LJPs, particularly LJP-1, exert strong inhibitory effects on liver cancer growth in vivo and in vitro. LJP-1 induces HCC cell apoptosis through the caspase-dependent pathway and G0/G1 arrest. LJP-1 induces caspase-dependent apoptosis, in part by inhibiting PI3K, MAPK signaling pathways, and cell cycle proteins. LJP-1 has the potential to be a novel candidate for human liver cancer therapeutics.

Biochemical and histopathological studies of sulfonylurea derivative as a new chemotherapeutic agent against liver cancer in free- and nano-coated forms

The most frequent type of primary liver cancer is hepatocellular carcinoma (HCC), accounting for approximately 90% of primary liver cancers and a third leading cause of cancer deaths. In the current study, the synthesized compound 3 was re-formulated using tetraethyl orthosilicate (TEOS) with weight ratio (1:1) via sol-gel technique. The prepared material has been examined using Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray elemental analysis (EDX), and scanning and transmission electron microscopes (SEM and TEM). Herein, we investigate the mode of action of 3 as potent anti-liver cancer in vivo as normal and nano-forms. Rats were given a single dosage of 50 mg/kg b.wt. of HCC through an intraperitoneal injection (ip). A single dosage of CCl4 (2 ml/kg IP) was also given to rats 2 weeks later. Several liver, tumor and oxidative stress biomarkers were detected including liver enzymes; alanine and aspartate aminotransferases (ALT and AST), alkaline phosphatse (ALP), gamma glutamyl transferase (GGT), glutathione (GSH), lipid peroxide (MDA), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), α-fetoprotein and α-L-Fucosidase. Hepatic pathological pictures were also performed for the documentation of the presence of HCC and supported the biochemical results. Moreover, the DNA damage in liver tissues of male rats using comet assay was studied. The results showed that the HePG2 (− ve) group of rats exhibited a significant reduction (P < 0.05) in DNA damage values (9.30 ± 0.89) relative to other treatment groups. Nevertheless, the DNA damage values in the HePG2 (+ ve) and 5-flurouracil groups were significantly higher (P < 0.01) compared to the HePG2 (− ve) group. Additionally, HePG2 (coated 3) and HePG2 (3) groups exhibited significant decrease in the DNA damage compared to those in HePG2 (+ ve) group.

NiO@TPP-HPA as an Efficient Integrated Nanocatalyst and Anti-Liver Cancer Agent. Synthesis of 2-Substituted Indoles

A new tetraphenylporphyrin-heteropolyacid (TPP-HPA) nanohybrid material is synthesized and loaded onto NiO nanoparticles to achieve an efficient heterogeneous catalyst. Then, the new inorganic-organic nanohybrid catalyst NiO@TPP-HPA was introduced as an efficient and recoverable catalyst in the synthesis of 2-substituted indoles through condensation of indole with malononitrile and different aldehydes at solventless condition. The nanohybrid material was characterized by FESEM, EDS, XRD, FTIR and TGA. The attained findings showed that NiO@TPP-HPA is an effective catalyst toward the desired condensation reaction and provided good recyclability for at least six runs without significant loss of activity. Moreover, it has been shown that preparation of 2-substituted indoles occurs by the way of radical mechanism, indicating •O2 −, h+ and OH• as contributing species. In addition, the hot-filtration experiment proved that NiO@TPP-HPA is a steady nanocatalyst in the current multicomponent synthesis. Moreover, the in-vitro toxicity of NiO@TPP-HPA was inspected toward HepG2 cell line through an MTT assay, confirming that this nanomaterial is a potential agent against the desired cell line. Therefore, this nanocomposite can be treated as an anti-liver cancer agent.

Effects of Sensitized Sorafenib with a Paeoniflorin and Geniposide Mixture on Liver Cancer via the NF-κB-HIF-2α-SerpinB3 Pathway.

Purpose This study focused on determining the anticancer effect of paeoniflorin and geniposide mixture (PFGS) combined with sorafenib (Sor) in hepatocellular carcinoma (HCC) and, in particular, whether PFGS increases the antitumor effect of Sor by modulating the NF-κB/HIF-2α/SerpinB3 pathway. Methods The H22 hepatoma tumor-bearing mouse model was treated with PFGS, Sor, and a combination of the two drugs for 12 days. The effects of PFGS combined with Sor on tumor growth and apoptosis and the expression of NF-κB, HIF-2α, and SerpinB3 in tumor tissue were assessed. In addition, Sor-resistant hepatoma cells were treated with PFGS, Sor, and the combination of the two drugs in vitro. The effects of PFGS combined with Sor on cell proliferation and invasion and the protein expression of NF-κB p65, HIF-2α, and SerpinB3 were investigated. Results PFGS combined with Sor treatment synergistically inhibited tumor growth in HCC tumor-bearing mice. Immunostaining showed that PFGS combined with Sor treatment significantly decreased the expression of Ki-67 and obviously induced apoptosis in the tumor compared with a single treatment. Similarly, PFGS combined with Sor treatment significantly downregulated the expression of NF-κB, HIF-2α, and SerpinB3 in the tumor compared with a single treatment. Additionally, PFGS combined with Sor markedly inhibited cell proliferation and invasion and activation of the NF-κB/HIF-2α/SerpinB3 pathway in Sor-resistant hepatoma cells compared with a single treatment. Conclusion Our study demonstrated that PFGS synergistically increased the antiliver cancer effects of Sor by lowering activation of the NF-κB/HIF-2α/SerpinB3 pathway. These findings provided a scientific foundation for clinical studies using PFGS and Sor to treat liver cancer.

Concanavalin A inhibits human liver cancer cell migration by regulating F-actin redistribution and assembly via MAPK signaling pathway.

Concanavalin A (Con A), the first and most typical representative of the legume lectin family, has a potent anti-liver cancer effect by inducing cell apoptosis and autophagy. However, its function in human liver cancer cell migration remains unclear. The present study investigated the effect of Con A on the viability and migration of human liver cancer cells with different metastatic abilities. It was found that Con A could reduce the viability of human liver cancer cells (HCCLM3, MHCC97L and HepG2) and human hepatocytes (MIHA). In addition, Con A could inhibit human liver cancer cell migration specifically without affecting hepatocytes. Sugar inhibition assay showed that glucose-related sugar binding sites played an important role in the inhibition of Con A on human liver cancer cell migration. In addition, Con A could affect HCCLM3 migration by activating ERK1/2, JNK1/2/3 and p38 signaling in the MAPK pathway. Moreover, Con A could regulate fibrous actin (F-actin) redistribution and assembly via the MAPK signaling pathway. However, Con A had no significant effect on the activation of matrix metalloproteinase (MMP)-2 and MMP-9 in HCCLM3 cells. In conclusion, Con A may bind to glucose-related receptor protein, activating ERK1/2, JNK1/2/3 and p38 signaling in the MAPK pathway, further contracting cells and reducing the content of F-actin of single cells to inhibit HCCLM3 cell migration. These results would deepen the links between human liver cancer cell migration and related glycoproteins or signaling molecules, and may provide a new perspective for Con A as a potential anticancer agent.

Investigation of Anti-Liver Cancer Activity of the Herbal Drug FDY003 Using Network Pharmacology.

Globally, liver cancer (LC) is the sixth-most frequently occurring and the second-most fatal malignancy, responsible for 0.83 million deaths annually. Although the application of herbal drugs in cancer therapies has increased, their anti-LC activity and relevant mechanisms have not been fully studied from a systems perspective. To address these issues, we conducted a system-perspective network pharmacological investigation into the activity and mechanisms underlying the action of the herbal drug. FDY003 reduced the viability of human LC treatment. FDY003 reduced the viability of human LC cells and elevated their chemosensitivity. There were a total of 16 potential bioactive chemical components in FDY003 and they had 91 corresponding targets responsible for the pathological processes in LC. These FDY003 targets were functionally involved in regulating the survival, proliferation, apoptosis, and cell cycle of LC cells. Additionally, we found that FDY003 may target key signaling cascades connected to diverse LC pathological mechanisms, namely, PI3K-Akt, focal adhesion, IL-17, FoxO, MAPK, and TNF pathways. Overall, this study contributed to integrative mechanistic insights into the anti-LC potential of FDY003.

Duguetia pycnastera Sandwith (Annonaceae) Leaf Essential Oil Inhibits HepG2 Cell Growth In Vitro and In Vivo.

Duguetia pycnastera Sandwith (Annonaceae) is a tropical tree that can be found in the Guyanas, Bolivia, Venezuela, and Brazil. In Brazil, it is popularly known as “ata”, “envira”, “envira-preta”, and “envira-surucucu”. In the present work, we investigated the in vitro and in vivo HepG2 cell growth inhibition capacity of D. pycnastera leaf essential oil (EO). The chemical composition of the EO was determined by GC–MS and GC–FID analyses. The alamar blue assay was used to examine the in vitro cytotoxicity of EO in cancer cell lines and non-cancerous cells. In EO-treated HepG2 cells, DNA fragmentation was measured by flow cytometry. The in vivo antitumor activity of the EO was assessed in C.B-17 SCID mice xenografted with HepG2 cells treated with the EO at a dosage of 40 mg/kg. Chemical composition analysis displayed the sesquiterpenes α-gurjunene (26.83%), bicyclogermacrene (24.90%), germacrene D (15.35%), and spathulenol (12.97%) as the main EO constituents. The EO exhibited cytotoxicity, with IC50 values ranging from 3.28 to 39.39 μg/mL in the cancer cell lines SCC4 and CAL27, respectively. The cytotoxic activity of the EO in non-cancerous cells revealed IC50 values of 16.57, 21.28, and >50 μg/mL for MRC-5, PBMC, and BJ cells, respectively. An increase of the fragmented DNA content was observed in EO-treated HepG2 cells. In vivo, EO displayed tumor mass inhibition activity by 47.76%. These findings imply that D. pycnastera leaf EO may have anti-liver cancer properties.

De-O-methyllasiodiplodin from Ludwigia hyssopifolia causes death of human liver cancer cells through the mitochondrial apoptotic, Akt/NF-κB and STAT3 pathway in vitro

(+)-(R)-de-O-methyllasiodiplodin (DOML), isolated from the Chinese herbal medicine Ludwigia hyssop folia, has great potential for development in pharmacological research on hepatocellular carcinoma (HCC). In our study, the CCK-8 assay, morphological observation, flow cytometry (also known as Annexin V-FITC/PI double staining), as well as Western blotting were adopted to study the anti-liver cancer activity and mechanisms of DOML on HepG2 and HuH-7 cells. The research exhibited that DOML dose- and time-dependently reduced the cell viability of HCC cells. DOML treatment resulted in changes in cell morphology, such as irregular edges, reduced volume, and decreased adhesion were observed under the microscope. Flow cytometry analysis indicated that apoptosis is the major form of cell death. In addition, blocking autophagy and necroptosis pathways couldn’t alleviate DOML-induced apoptosis. Protein expression levels of Bax, activated Caspase-3 and Caspase-9, and PARP were increased, while Bcl-2 protein levels were reduced by DOML treatment, which suggested that the mitochondrial apoptotic pathway may be involved in DOML-induced cell death. Moreover, the expression of NF-κB and the phosphorylation of Akt and STAT3 decreased with the increase of dosage, suggesting that the apoptotic mechanism might be related to the Akt/NF-κB and STAT3 signaling pathways. All these results indicate that DOML has the potential effects of anti-hepatoma.

Synthesis and biological activity evaluation of podophyllotoxin-linked bile acid derivatives as potential anti-liver cancer agents

Podophyllotoxin’s undifferentiated cytotoxicity and poor selectivity limit its clinical application. To improve above disadvantages, conjugation of bile acids with podophyllotoxin could improve cell line selectivity of liver cancer to achieve clinical translation further. Enlightened by the bile acids’ moiety magic characters, thirty podophyllotoxin-linked bile acid derivatives had been designed and synthesized. The cytotoxicity of these compounds in vitro was evaluated on HepG2, HCT-116, A549 and MDCK cell lines. After conjunction with bile acids, most of the derivatives (IC50 = 0.066–0.831 μM) were more potent against above three types of tumor cells than Etoposide (VP-16, IC50 = 4.319–41.080 μM) and exhibited similar antitumor activity compared with doxorubicin (DOX, IC50 = 0.230–0.745 μM). Moreover, structure–activity relationship displayed the length of the linker chain between podophyllotoxin and bile acids affected the cytotoxicity. Especially, compound 23 exhibited strong activity against HepG2 cell lines (IC50 = 0.188 ± 0.01 μM) than MDCK cell lines (IC50 = 4.780 ± 0.50 μM) and its SI (IC50MDCK/IC50HepG2) value of compound 23 was 25.4. Further antitumor mechanism studies showed that compound 23 acted as Topo Ⅱ inhibition and induced cell apoptosis with S cell cycle arrest. In particular, compound 23 showed valid antitumor efficacy at 10 mg/kg by intraperitoneal administration with a tumor inhibition rate of 60.9% in the Hepa1-6 xenograft mice model. The current research displayed that introduction of bile acids contributed to improve selectivity and activity to cell, and compound 23 could be a promising anti-tumor candidate.

Preparation of polydopamine-modified celastrol nanosuspension and its anti-liver cancer activity in vitro

Celastrol (CEL) is one of the main effective components of traditional Chinese medicine Tripterygium wilfordii Hook.f, which has high antitumor activity. However, its low solubility and low bioavailability limit its clinical use. In this study, a CEL nanosuspension (PDA@CEL-NS) with near-infrared photothermal properties was prepared. PDA@CEL-NS contained spherical nanoparticles with an average particle size of 189.67 nm, zeta potential of −30.23 mV, and 60.33% drug loading. X-ray diffraction showed that PDA@CEL-NS had an amorphous structure. PDA@CEL-NS had good stability after storage at 4 °C and 37 °C for 30 days, and there was no aggregation or sedimentation in a 5% glucose solution or culture medium. The highly dispersed nanoparticles greatly improved dissolution in vitro, and the cumulative release rate of PDA@CEL-NS over 72 h was as high as 60.10%. It demonstrated both high release and a good sustained-release effect. Cell experiments showed that PDA@CEL-NS had stronger efficacy than CEL-NS or CEL, and the efficacy was further enhanced after laser application. Nuclear rupture and deformation and the induction of apoptosis were potential toxic mechanisms, and they also inhibited cell migration. In conclusion, PDA@CEL-NS is expected to become a nano-drug delivery system for the treatment of cancer.

Extraction, characterization, and in vivo antitumor activity of a novel polysaccharide from Coriandrum sativum L.

A novel polysaccharide was extracted from Coriandrum sativum L. at a yield of 4.56 ± 0.17% (n= 3). The extraction was optimized using response surface methodology: powder-to-liquid ratio 1:21 g/ml, extraction time 188 min, temperature 81°C, and three replicate extractions. The purified polysaccharide had an average molecular weight of 1.30 × 106 Da and was composed of rhamnose, arabinose, galactose, glucose, and galacturonic acid in molar ratios of 1.52: 8.14: 20.85: 1: 2.42 with α-L-Araf-(1→, →6)-β-D-Galp-(1→, →4)-α-GalpA-(1→ and →2, 4)-α-Rhap-(1→). In vivo tests demonstrated that the polysaccharide suppressed H22 tumor growth in mice and protected the immune organs. Annexin V-FITC/PI, PI, and JC-1 staining showed that the primary mechanism of tumor inhibition was the induction of apoptosis and S-phase arrest with apoptosis achieved via a mitochondrial pathway. PRACTICAL APPLICATIONS: Coriandrum sativum L. is used as a culinary spice but its medicinal value has also been widely recognized. A novel polysaccharide was extracted from this herbaceous plant and its structure and bioactivity were investigated. This high-molecular-weight polysaccharide exhibited antitumor effects against H22 cells in mice and had potential to be developed as an anti-liver cancer medicine and functional food supplement.

Antitumor Effect of Guatteria olivacea R. E. Fr. (Annonaceae) Leaf Essential Oil in Liver Cancer.

Guatteria olivacea R. E. Fries (synonym Guatteria punctata (Aubl.) R.A. Howard) is a tree of 10–27 m tall popularly known as “envira-bobó”, “envira-fofa”, “envireira”, “embira”, “embira-branca”, “embira-preta”, envira-branca”, and “envira-preta”, which can be found in the Brazilian Amazon biome. In this study, we evaluated the cytotoxic and antitumor effects of the essential oil (EO) obtained from the leaves of G. olivacea against liver cancer using HepG2 cells as a model. EO was obtained using a hydrodistillation Clevenger-type apparatus and was qualitatively and quantitatively characterized using GC–MS and GC–FID, respectively. The alamar blue assay was used to assess the cytotoxic potential of EO in a panel of human cancer cell lines and human non-cancerous cells. In HepG2 cells treated with EO, YO-PRO-1/propidium iodide staining, cell cycle distribution, and reactive oxygen species (ROS) were examined. In C.B-17 SCID mice with HepG2 cell xenografts, the efficacy of the EO (20 and 40 mg/kg) was tested in vivo. GC–MS and GC–FID analyses showed germacrene D (17.65%), 1-epi-cubenol (13.21%), caryophyllene oxide (12.03%), spathulenol (11.26%), (E)-caryophyllene (7.26%), bicyclogermacrene (5.87%), and δ-elemene (4.95%) as the major constituents of G. olivacea leaf EO. In vitro cytotoxicity of EO was observed, including anti-liver cancer action with an IC50 value of 30.82 μg/mL for HepG2 cells. In HepG2 cells, EO treatment increased apoptotic cells and DNA fragmentation, without changes in ROS levels. Furthermore, the EO inhibited tumor mass in vivo by 32.8–57.9%. These findings suggest that G. olivacea leaf EO has anti-liver cancer potential.

Canthaxanthin shows anti-liver aging and anti-liver fibrosis effects by down-regulating inflammation and oxidative stress in vivo and in vitro

The elderly population is growing rapidly all over the world. The aging population has brought great medical pressure to the society. It is found that aging is one of the pathogenic factors of liver fibrosis and liver cancer. Therefore, it is very important to explore functional foods with anti-aging, anti-fibrosis and anti-liver cancer effect. Therefore, in this work, we studied the potential effects of Canthaxanthin on liver aging, liver fibrosis and liver cancer. Firstly, we established the aging modelof liver cells by using H2O2. On this basis, the anti-aging effect of Canthaxanthin was analyzed, and the results showed that Canthaxanthin could significantly alleviate the aging of liver cells through Sa-β-Gal staining and analysis of the expression of aging related markers. In vivo, aged mice wereused as the animal model for studying the effect of anti-aging of Canthaxanthin. The results showed that Canthaxanthin could significantly alleviate the aging of liver in vivo. Further study show that Canthaxanthin may alleviatethe aging of liver cells by regulating SIRT6; Secondly, we evaluated the effect of Canthaxanthin on liver fibrosis. A model of liver fibrosis was established by CCl4. Masson and Sirius red staining showed that Canthaxanthin could significantly reduce the fibrosis area. Additionally, the level of liver inflammation was also reduced; Thirdly, the effect of Canthaxanthin on hepatoma cells has also been investigated. The resultsshowed that Canthaxanthin could promote the apoptosis of hepatoma cells in vivo and in vitro. To sum up, these results show that canthaxanthin can significantly alleviate liver aging and fibrosis, and Canthaxanthin can also promote the apoptosis of liver cancer cells, indicating that Canthaxanthin can be used as a potential drug or health food for the treatment of liveraging related diseases.

Mechanism of Bupleurum scorzonerifolium and Paeonia lactiflora herbal pair against liver cancer: an exploration based on UPLC-Q-TOF-MS combined with network pharmacology

This study aimed to decipher the pharmacodynamic material basis and mechanism of herbal pair Bupleurum scorzonerifolium-Paeonia lactiflora(BS-PL) against liver cancer based on UPLC-Q-TOF-MS and network pharmacology. MTT assay and human hepatocellular carcinoma HepG2 cells were used to screen the effective part of BS-PL, the active components of which were further analyzed and identified by UPLC-Q-TOF-MS. Next, we applied Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the active ingredients with OB≥30%. Then TCMSP and SwissTargetPrediction were used to collect and predict component targets, followed by the search of liver cancer-related targets with GeneCards and DisGeNET. The intersection targets were obtained using Venny 2.1.0. Protein-protein interaction(PPI) network was constructed using STRING to uncover the core targets, which were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis based on DAVID. Finally, the effects of active ingredients on the expression of main proteins enriched in the key pathways of HepG2 cells were verified by Western blot. The results indicated that compared with 30%, 50%, and 70% ethanol extracts of BS-PL, the n-butanol extraction part(CSYZ) from 95% ethanol extract of BS-PL exhibited the best anti-tumor effect. UPLC-Q-TOF-MS revealed 31 ingredients, 14 of which showed OB≥30%. A total of 220 intersection targets were obtained, from which 35 were selected as the key targets under the condition of two times the median of degree. Among the 215 items with P&lt;0.05 obtained through GO enrichment analysis, 154 were classified into biological processes, 22 into cell components and 39 into molecular functions. KEGG enrichment analysis revealed 95 significantly affected signaling pathways, and the ones(sorted in a descending order by P value) closely related to the anti-liver cancer effect of herbal pair were PI3 K-AKT signaling pathway, TNF signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, and ErbB signaling pathway. Finally, the PI3 K/AKT signaling pathway involving the largest number of targets was extrapolated, and it was found that this pathway contained 15 core targets and 8 active components. Experimental verification showed that the effective components of BS-PL significantly inhibited the expression of p-PI3 K and p-AKT, consistent with the prediction results of network pharmacology. In conclusion, the main pharmacodynamic substances of BS-PL against liver cancer are 14 components like saikosaponin a, saikosaponin d, and paeoniflorin, which exert the anti-liver cancer effect by regulating PI3 K/AKT pathway.

Synergetic HepG2 cells suppression efficacy of Tripterygium wilfordii and Scutellaria barbata through EGFR/PI3K/Akt pathway

Traditional Chinese medicines (TCMs) Tripterygium wilfordii Hook. f. (TW) and Scutellaria barbata D. Don (SB) are reported to have anticancer activity. However, the synergetic anti-liver cancer efficacy is still unknown. Herein, we demonstrated that the combination of TW and fermentation product of SB by yeast (TW+SB) could markedly improve the HepG2 cell suppression capacity as compared to individual TW or SB. Hence, synergetic mechanisms of TW+SB combination were further investigated by systems pharmacology, LC-MS, etc. The results showed that fermentation increases the concentration of active components of SB rather than those of TW, leading to the increase of HepG2 cell inhibition efficacy of SB. TW+SB combination effectively suppresses proliferation, migration, and invasion of liver cancer cells by inducing EGFR/PI3K/Akt signaling pathway mediated apoptosis. In conclusion, TW+SB combination showed outstanding synergetic anti-liver cancer effect, and it might offer a promising treatment option for cancer patients.