Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer Cells.

Oncolytic viruses (OVs) and phytochemical ursolic acid (UA) are two efficacious therapeutic candidates in development against breast cancer, the deadliest women's cancer worldwide. However, as single agents, OVs and UA have limited clinical efficacies. As a common strategy of enhancing monotherapeutic anticancer efficacy, we explored the combinatorial chemovirotherapeutic approach of combining oncolytic measles virus (MV), which targets the breast tumor marker Nectin-4, and the anticancer UA against breast adenocarcinoma. Our findings revealed that in vitro co-treatment with UA synergistically potentiated the killing of human breast cancer cells by oncolytic MV, without UA interfering the various steps of the viral infection. Mechanistic studies revealed that the synergistic outcome from the combined treatment was mediated through UA's potentiation of apoptotic killing by MV. To circumvent UA's poor solubility and bioavailability and strengthen its clinical applicability, we further developed UA nanoparticles (UA-NP) by nanoemulsification. Compared to the non-formulated UA, UA-NP exhibited improved drug dissolution property and similarly synergized with oncolytic MV in inducing apoptotic breast cancer cell death. This oncolytic potentiation was partly attributed to the enhanced autophagic flux induced by the UA-NP and MV combined treatment. Finally, the synergistic effect from the UA-NP and MV combination was also observed in BT-474 and MDA-MB-468 breast cancer cells. Our study thus highlights the potential value of oncolytic MV and UA-based chemovirotherapy for further development as a treatment strategy against breast cancer, and the feasibility of employing nanoformulation to enhance UA's applicability.

Targeting Autophagy Augments BBR-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA.

Hepatocellular carcinoma (HCC), including hepatitis C virus (HCV)-induced HCC, is a deadly disease highly refractory to chemotherapy, thus requiring the continuous identification of novel treatment strategies. Berberine (BBR) has been previously reported to inhibit hepatoma cell growth, but the main type of cell death elicited by BBR, and whether the alkaloid can inhibit hepatoma cells carrying HCV genomes, is unclear. Herein, we show that BBR treatment induced a biphasic cell death irrespective of the presence of HCV subgenomic replicon RNA, first triggering apoptosis that then progressed to necrosis between 24 and 48 h post-treatment. Furthermore, BBR treatment potentiated the HCV replicon-induced reactive oxygen species (ROS) production, inhibition of which with an antioxidant attenuated the cell death that was elicited by BBR in these cells. Moreover, BBR dampened the autophagic response in HCV RNA-positive or negative hepatoma cells, and pharmacological inhibition of autophagy conversely augmented the BBR-induced cell death. Finally, BBR inhibited the growth of Huh-7 cells that were persistently infected with the full-length genome HCV particles, and concomitant pharmacological inhibition of autophagy potentiated the killing of these cells by BBR. Our findings suggest that combining BBR with the inhibition of autophagy could be an attractive treatment strategy against HCC, irrespective of the presence of the HCV genome.

Taiwanofungus camphoratus Combined With Amphotericin B for Metastatic Cancer Patients Unresponsive to or Unwilling to Undergo Chemotherapy: A Pilot Study.

CONTEXT: Taiwanofungus camphoratus is a parasitic mushroom found in the heartwood of Cinnamomum kanehirai and is used as a nutritional supplement. It has an anticancer action, both alone and synergistically with amphotericin B (AmB). OBJECTIVE: The study intended to assess the efficacy of a T camphoratus ethanol extract (TCEE) combined with AmB for patients with metastatic cancer whose cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy. DESIGN: The research team performed a retrospective analysis as a pilot study. SETTING: The study took place at a single hospital (Taipei Medical University Hospital, Taipei, Taiwan). PARTICIPANTS: Participants were 9 patients at the hospital who were terminally ill with metastatic cancer. INTERVENTIONS: The participants had received daily doses of 2-3 g of the TCEE in combination with a weekly dose of 20-25 mg of AmB in 500 cc of 5% glucose water, given intravenously in 4-6 h. OUTCOME MEASURES: Outcome measures included (1) a primary evaluation index measuring the efficacy of the treatment; (2) a measure of tumor burden that was estimated using the response evaluation criteria in solid tumors (RECIST 1.1), (3) a secondary evaluation index measuring survival duration, and (4) safety. RESULTS: The mean treatment time was 54.4 ± 18.3 wk. At the end of the study, 2 patients showed a continued complete response, 1 patient had a continued partial response, and 1 patient showed a stable disease. The other 5 participants had times to progression ranging from 24 to 48 wk, with a mean of 35.6 wk. The mean survival time was 57.8 ± 18.5 wk, and 5 patients were still alive at the end of the study. CONCLUSIONS: For patients whose metastatic cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy, the use of TCEE as an adjuvant therapy to AmB resulted in tumor suppression and a delay in time to disease progression. The preliminary results reported here can be used to guide a future, more extensive clinical study of the combination.

Polysaccharides obtained from mycelia of Cordyceps militaris attenuated doxorubicin-induced cytotoxic effects in chemotherapy.

OBJECTIVES: Fungus Cordyceps militaris has been used as a herbal tonic in traditional Chinese medicine, which could be surface liquid-cultured for mycelia production. To evaluate the potential of polysaccharides obtained from mycelia of Cordyceps militaris (PS-MCM) for attenuation of side-effects of chemotherapy. METHODS: Doxorubicin was used to induce cytotoxicity in THP-1 monocytes and EL-4 T cells, and the effects of PS-MCM on cell viability and cytokine production were detected on doxorubicin-treated THP-1 and EL-4 cells. RESULTS: PS-MCM reduced doxorubicin-induced cell death and promoted cell proliferation in THP-1 and EL-4 cells. Moreover, PS-MCM elevated the level of cytokines associated with immune-modulation of THP-1 and EL-4 cells. CONCLUSION: These findings indicate that PS-MCM has potential for development as a functional food to counteract side effects of chemotherapy.

Paris Polyphylla Inhibits Colorectal Cancer Cells via Inducing Autophagy and Enhancing the Efficacy of Chemotherapeutic Drug Doxorubicin.

Colorectal cancer is one of the most common cancers worldwide and chemotherapy is the main approach for the treatment of advanced and recurrent cases. Developing an effective complementary therapy could help to improve tumor suppression efficiency and control adverse effects from chemotherapy. Paris polyphylla is a folk medicine for treating various forms of cancer, but its effect on colorectal cancer is largely unexplored. The aim of the present study is to investigate the tumor suppression efficacy and the mechanism of action of the ethanolic extract from P. polyphylla (EEPP) in DLD-1 human colorectal carcinoma cells and to evaluate its combined effect with chemotherapeutic drug doxorubicin. The data indicated that EEPP induced DLD-1 cell death via the upregulation of the autophagy markers, without triggering p53- and caspase-3-dependent apoptosis. Moreover, EEPP treatment in combination with doxorubicin enhanced cytotoxicity in these tumor cells. Pennogenin 3-O-beta-chacotrioside and polyphyllin VI were isolated from EEPP and identified as the main candidate active components. Our results suggest that EEPP deserves further evaluation for development as complementary chemotherapy for colorectal cancer.

Chemovirotherapeutic Treatment Using Camptothecin Enhances Oncolytic Measles Virus-Mediated Killing of Breast Cancer Cells.

Oncolytic virotherapy represents an emerging development in anticancer therapy. Although it has been tested against a variety of cancers, including breast cancer, the efficacy of oncolytic viral vectors delivered as a monotherapy is limited. Enhancing viral oncolytic therapies through combination treatment with anticancer agents is a feasible strategy. In this study, we considered a chemovirotherapeutic approach for treating breast adenocarcinoma using oncolytic measles virus (MV) and the chemotherapeutic agent camptothecin (CPT). Our results demonstrated that co-treatment of MV with CPT yielded enhanced cytotoxicity against breast cancer cells. Low dosage CPT combined with MV was also found to elicit the same therapeutic effect as high doses of CPT. At the lower dosage used, CPT did not inhibit the early stages of MV entry, nor reduce viral replication. Further studies revealed that co-treatment induced significantly enhanced apoptosis of the breast cancer cells compared to either MV or CPT alone. Overall, our findings demonstrate the potential value of MV plus CPT as a novel chemovirotherapeutic treatment against breast cancer and as a strategy to enhance MV oncolytic activity.

Pardaxin Promoted Differentiation and Maturation of Leukemic Cells via Regulating TLR2/MyD88 Signal against Cell Proliferation.

OBJECTIVE: Leukemia is a cancer of the blood cells. Leukemic THP-1 and U937 cells were used in this study as monocytic effectors cells for proliferation responses and macrophage-like cells induction in leukemia. Pardaxin is an antimicrobial peptide isolated from the marine fish species. METHODS: After treatment for 5 days, pardaxin significantly suppressed cell viability and arrested cell cycle at G0/G1 phase in leukemic cells which were evaluated. RESULTS: Pardaxin also induced cell differentiation and maturation of THP-1 and U937 cells into macrophage-like cells with phagocytotic ability. Moreover, pardaxin elevated the expression of MyD88 but not toll-like receptor (TLR)-2 in both leukemic cells. TLR-2 blocking peptide was used to confirm that pardaxin attenuated phagocytotic ability and superoxide anion production in leukemic cells via activating MyD88 protein. CONCLUSIONS: These findings suggested that pardaxin has a therapeutic potential for leukemia.

Symptom severity, symptom interference and use of complementary and alternative medicine among survivors of colorectal and breast cancer after curative treatment in Taiwan.

This study compared symptom severity, symptom interference and use of complementary and alternative medicine (CAM) between cancer survivors after curative treatment and individuals who did not have cancer. Factors associated with CAM use among cancer survivors were examined. A cross-sectional survey was conducted of 146 cancer survivors (77 breast and 69 colorectal cancer survivors who had completed conventional treatment 1-5 years previously and were cancer-free) from a hospital's cancer registration system (survivor group), and 161 healthy individuals without cancer (comparison group). The two groups were frequency-matched for sex and age. Findings indicated higher use of CAM in the survivor group (54.1%) than the comparison group (36.6%). There were no significant differences in overall symptom severity and interference between the two groups. Multivariate logistic regression showed that prior use of CAM (OR = 5.14, 95% CI: 2.34-10.69) and higher symptom interference (OR = 1.04, 95% CI: 1.001-1.08) were positively related to CAM use in the survivor group. The survivors did not have higher symptom severity and symptom interference with daily life, but were more likely to use CAM than the comparison group. Medical staff should discuss symptom interference and use of CAM with cancer survivors to guide them in the appropriate use of CAM.

Innovatively Therapeutic Strategy on Lung Cancer by Daily Drinking Antioxidative Plasmon-Induced Activated Water.

Many human diseases are inflammation-related, such as cancer and those associated with aging. Previous studies demonstrated that plasmon-induced activated (PIA) water with electron-doping character, created from hot electron transfer via decay of excited Au nanoparticles (NPs) under resonant illumination, owns reduced hydrogen-bonded networks and physchemically antioxidative properties. In this study, it is demonstrated PIA water dramatically induced a major antioxidative Nrf2 gene in human gingival fibroblasts which further confirms its cellular antioxidative and anti-inflammatory properties. Furthermore, mice implanted with mouse Lewis lung carcinoma (LLC-1) cells drinking PIA water alone or together with cisplatin treatment showed improved survival time compared to mice which consumed only deionized (DI) water. With the combination of PIA water and cisplatin administration, the survival time of LLC-1-implanted mice markedly increased to 8.01 ± 0.77 days compared to 6.38 ± 0.61 days of mice given cisplatin and normal drinking DI water. This survival time of 8.01 ± 0.77 days compared to 4.62 ± 0.71 days of mice just given normal drinking water is statistically significant (p = 0.009). Also, the gross observations and eosin staining results suggested that LLC-1-implanted mice drinking PIA water tended to exhibit less metastasis than mice given only DI water.

Inhibition of aqueous extracts of Solanum nigrum (AESN) on oral cancer through regulation of mitochondrial fission.

The present study is designed to investigate the anti-oral cancer properties of Solanum nigrum on oral squamous cell carcinoma. S. nigrum is a Chinese herb used for suppression of various cancers. However, the inhibition of S. nigrum on oral cancer is unclear. Therefore, human oral squamous cancer cells (SCC)-4 were used to evaluate the effect of aqueous extracts of S. nigrum (AESN) on cancer cell proliferation, cell cycle, mitochondrial function and apoptosis. The SCC-4 cells were treated by AESN to evaluate the inhibition of cell proliferation and mitochondrial function in vitro. Our results suggested that AESN markedly increased reactive oxygen species production. AESN also promoted caspase-9 and caspase-3 activation and subsequent triggering of the mitochondrial apoptotic pathway. The inhibition of glucose uptake was alleviated mediated by a dose-dependent manner in SCC-4 cells with AESN treatment for 24 h, resulting in mitochondrial fission. These results suggested that AESN has potential to be used as a functional food in adjuvant chemotherapy for treating human oral cancer by suppression of mitochondrial function.

Maspin Enhances the Anticancer Activity of Curcumin in Hormone-refractory Prostate Cancer Cells.

BACKGROUND/AIM: Androgen deprivation therapy remains the principal treatment for patients with advanced prostate cancer, though, most patients will eventually develop hormone-refractory prostate cancer (HRPC). Androgen ablation mediated maspin-induction has been identified in cancer patients. However, the role of maspin on the anticancer activity of curcumin derived from turmeric (Curcuma longa) in HRPC cells has not been elucidated. MATERIALS AND METHODS: The anticancer action of curcumin in hormone-independent prostate cancer cells (DU145, and PC-3) was determined by measures of cell survival rate. The cause of maspin silencing on the anti-tumor abilities of curcumin in PC-3 cells was evaluated by measures of cell survival rate, cell-cycle distribution, and apoptosis signaling analysis. RESULTS: Our present study showed that PC-3 cells (with higher maspin expression) were more sensitive than DU145 cells to curcumin treatment (with lower maspin expression). RNA interference-mediated maspin silencing reduced curcumin sensitivity of PC-3 cells, as evidenced by reduced apoptotic cell death. After exposure to curcumin, maspin-knockdown cells showed lower expression levels of pro-apoptotic proteins, Bad and Bax, as compared with control cells. CONCLUSION: Maspin can enhance the sensitivity of HRPC cells to curcumin treatment.

Cancer-related pain: a nationwide survey of patients' treatment modification and satisfaction in Taiwan.

BACKGROUND: We have limited knowledge about cancer patients' pain control satisfaction in outpatient departments in Taiwan and doctors' practice of adjusting analgesics according to their pain status. This survey examined pain management and satisfaction among cancer outpatients with pain and obtained information on their quality of life and treatment management for different pain intensities. METHODS: The Short version of the Brief Pain Inventory was used as the outcome questionnaire. Participants comprised 2075 patients with different cancers and disease statuses at 14 oncological outpatient departments, of which 1051 reported pain within the week prior to testing. The impact of pain management on physical and psychological functioning, and satisfaction with doctors were evaluated. Information about doctors' prescriptions was collected. Logistic regression analyses were conducted to evaluate whether the interference scale performed identically in the different analgesic ladders. RESULTS: Pain was significantly linked to disease status and affected patients' physical and psychiatric functioning. Almost 100% of patients were satisfied with their pain control, but more than 70% of doctors did not change analgesics based on patients' current pain status. The results show that although patients were satisfied with their physicians, treatment of cancer pain was still suboptimal. CONCLUSION: Pain assessment and treatment need to be more thorough and management guidelines should be revised to improve pain control in patients with cancer.

Bevacizumab and cetuximab with conventional chemotherapy reduced pancreatic tumor weight in mouse pancreatic cancer xenografts.

Pancreatic cancer remains the fourth leading cause of cancer-related death in the USA with a 5-year survival rate of 5 %. The effects of epidermal growth factor receptor and vascular endothelial growth factor A blockade with chemotherapy on pancreatic tumor growth were examined. Mice bearing human PANC-1 cell xenografts were divided into three groups: T-CR (gemcitabine, cisplatin, and 5-fluorouracil), T-TR (cetuximab, bevacizumab, gemcitabine, cisplatin, and 5-fluorouracil), and vehicle control (T). The therapies were administered via intraperitoneal injections every 4 days for seven cycles from 7 weeks after cancer cell implantation. Mice treated with T-TR had significant reductions in tumor weight as compared to the control group (p < 0.05). Although mice in the T-CR group experienced a significant reduction in body weight gain, serum albumin, and gastrocnemius muscle mass (p < 0.05), no such reductions were observed in the T-TR group. Mice treated with T-TR had slightly increased CD11c+ DC and CD49b+ NK cell levels in the spleen (p < 0.05) and significantly lower tumor VEGF expression (p < 0.05). Tumor carcinoembryonic antigen expression was significantly reduced in both treatment groups (p < 0.05). Thus, addition of bevacizumab and cetuximab to gemcitabine, cisplatin, and fluorouracil may represent an effective treatment option for pancreatic cancer that warrants further study.

Highly bioavailable silibinin nanoparticles inhibit HCV infection.

OBJECTIVE: Silibinin is a flavonolignan that is well established for its robust antiviral activity against HCV infection and has undergone several clinical trials for the management of hepatitis C. Despite its potency, silibinin suffers from poor solubility and bioavailability, restricting its clinical use. To overcome this limitation, we developed highly bioavailable silibinin nanoparticles (SB-NPs) and evaluated their efficiency against HCV infection. DESIGN: SB-NPs were prepared using a nanoemulsification technique and were physicochemically characterised. Infectious HCV culture systems were used to evaluate the influence of SB-NP on the virus life cycle and examine their antioxidant activity against HCV-induced oxidative stress. The safety profiles of SB-NP, in vivo pharmacokinetic studies and antiviral activity against infection of primary human hepatocytes were also assessed. RESULTS: SB-NP consisted of nanoscale spherical particles (<200 nm) encapsulating amorphous silibinin at >97% efficiency and increasing the compound's solubility by >75%. Treatment with SB-NP efficiently restricted HCV cell-to-cell transmission, suggesting that they retained silibinin's robust anti-HCV activity. In addition, SB-NP exerted an antioxidant effect via their free radical scavenging function. Oral administration of SB-NP in rodents produced no apparent in vivo toxicity, and pharmacokinetic studies revealed an enhanced serum level and superior biodistribution to the liver compared with non-modified silibinin. Finally, SB-NP efficiently reduced HCV infection of primary human hepatocytes. CONCLUSIONS: Due to SB-NP's enhanced bioavailability, effective anti-HCV activity and an overall hepatoprotective effect, we suggest that SB-NP may be a cost-effective anti-HCV agent that merits further evaluation for the treatment of hepatitis C.

Contrast-Enhanced Ultrasound and Computed Tomography Assessment of Hepatocellular Carcinoma after Transcatheter Arterial Chemo-Embolization: A Systematic Review.

BACKGROUND AND AIMS: Contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) are used to assess the response of hepatocellular carcinoma after transarterial chemoembolization. Our aim was to perform a systematic review to compare CEUS and CECT for therapeutic response assessment to transarterial chemoembolization in the treatment of hepatocellular carcinoma. METHOD: PubMed, Embase, and the Cochrane Library databases were searched from inception until January 1, 2016. PARTICIPANTS: patients with hepatocellular carcinoma. INTERVENTION: transarterial chemoembolization and CECT vs CEUS. RESULTS: Sixteen studies were included in the systematic review. The total number of patients was 858 and the mean patient age ranged from 42 to 73 years. The mean tumor size ranged from 1.0 cm to 4.3 cm. The sensitivity and specificity of CEUS ranged from 46% to 100% and 65% to 100%, respectively, and that of CECT ranged from 34% to 87% and 92% to 100%, respectively. The accuracy of CEUS ranged from 72.6% to 100% and that of CECT from 61% to 94%. Marked heterogeneity was present among the studies. CONCLUSION: CEUS is comparable with CECT for the therapeutic response assessment after transarterial chemoembolization.

Highly Diverse Efficacy of Salvage Treatment Regimens for Relapsed or Refractory Peripheral T-Cell Lymphoma: A Systematic Review.

BACKGROUND: The goal of this study was to perform a systematic review to examine the efficacy and safety of various salvage therapy regimens on patients with relapsed/refractory PTCL. METHOD: The electronic searches were performed using PubMed, Cochrane Library, EMBASE, and Web of Science from inception through June 2015, with search terms related to relapsed/refractory PTCL, salvage chemotherapy regimens, and clinical trials. An eligible study met the following inclusion criteria: (1) Patients had refractory or relapsed PTCL; (2) drug regimens were used for salvage therapy; (3) the study was a clinical trial; (4) the study reported on a series of at least 10 patients of PTCL. RESULTS: Of 35 records identified, a total of 14 studies were eligible for systematic reviews, and 12 different salvage regimens were investigated. A total of 618 relapsed/refractory PTCL patients were identified. The ORRs ranged from 22% for those treated with lenalidomide to 86% for those with brentuximab vedotin. By the three most frequent subtypes, the ORRs ranged from 14.2% to 71.5% for patients with the PTCL-NOS subtype, 8% to 54% for AITL subtypes, and 24% to 86% for the ALCL subtype. The medians of DOR, PFS, and OS ranged from 2.5 to 16.6 months, 2.6 to 13.3 months, and 3.6 to 14.5 months, respectively. The most frequently reported grade 3 or 4 adverse events (AEs) were hematological AEs, such as neutropenia and thrombocytopenia. CONCLUSION: The efficacy of salvage therapy regimens is highly diverse for patients with relapsed/refractory PTCL; this heterogeneity in therapeutic effects might be due to the diversity in mechanisms, PTCL subtype distribution, and/or numbers/profiles of prior therapy. Comparative studies with matched pair analysis are warranted for more evidence of the salvage treatment effect on relapsed or heavily pretreated patients with PTCL.

Aqueous Extract of Paris polyphylla (AEPP) Inhibits Ovarian Cancer via Suppression of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator (PGC)-1alpha.

Chemotherapy, a major approach was used in carcinoma treatment, always involves the development of drug resistance as well as side-effects that affect the quality of patients' lives. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance was established recently. We demonstrate in this paper that the aqueous extract of Paris polyphylla (AEPP)-a traditional Chinese medicine-can be used in various cancer types for suppression of carcinogenesis. We evaluated the suppressions of EMT and mitochondrial activity by AEPP treatment in a high-glucose (HG) induced-human ovarian carcinoma cell line (OVCAR-3 cells). The mitochondrial morphology was investigated using MitoTracker Deep Red FM staining. Our results indicated that AEPP reduced the viability of OVCAR-3 cells considerably through induction of apoptosis. However, this inhibitory potential of AEPP was attenuated by HG induction in OVCAR-3 cells. The levels of estrogen-related receptor (ERR)-alpha activator and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha were elevated by HG induction, but were suppressed by AEPP treatment. Down-regulations of cell survival and EMT were oberved in OVCAR-3 cells through suppression of PGC-1alpha by AEPP treatment. These results were confirmed through PGC-1alpha knockdown and overexpression in OVCAR-3 cells. Thus, AEPP can be beneficial for treating ovarian cancer and has potential for development of an integrative cancer therapy against ovarian cancer proliferation, metastasis, and migration.

Anti-Cancer Activity of Solanum nigrum (AESN) through Suppression of Mitochondrial Function and Epithelial-Mesenchymal Transition (EMT) in Breast Cancer Cells.

Chemotherapy is the main approach for treating advanced and recurrent carcinoma, but the clinical performance of chemotherapy is limited by relatively low response rates, drug resistance, and adverse effects that severely affect the quality of life of patients. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance has been investigated in recent studies. Our recent studies have found that the aqueous extract of Solanum nigrum (AESN) is a crucial ingredient in some traditional Chinese medicine formulas for treating various types of cancer patients and exhibits antitumor effects. We evaluated the suppression of EMT in MCF-7 breast cancer cells treated with AESN. The mitochondrial morphology was investigated using Mitotracker Deep-Red FM stain. Our results indicated that AESN markedly inhibited cell viability of MCF-7 breast cancer cells through apoptosis induction and cell cycle arrest mediated by activation of caspase-3 and production of reactive oxygen species. Furthermore, mitochondrial fission was observed in MCF-7 breast cancer cells treated with AESN. In addition to elevation of E-cadherin, downregulations of ZEB1, N-cadherin, and vimentin were found in AESN-treated MCF-7 breast cancer cells. These results suggested that AESN could inhibit EMT of MCF-7 breast cancer cells mediated by attenuation of mitochondrial function. AESN could be potentially beneficial in treating breast cancer cells, and may be of interest for future studies in developing integrative cancer therapy against proliferation, metastasis, and migration of breast cancer cells.

The anti-hepatic fibrosis activity of ergosterol depended on upregulation of PPARgamma in HSC-T6 cells.

Advanced glycation endproducts (AGEs) were shown to play an important role in metabolic syndrome and were suggested to contribute to the development of hepatic fibrosis. Evidence indicates that AGEs resulted in hepatic fibrosis coupled to the activation of the receptor for AGEs (RAGE) in hepatic stellate cells (HSCs). NADPH oxidase is downstream of the RAGE signaling pathway, resulting in an increase in reactive oxygen species (ROS), alpha-smooth muscle actin (alpha-SMA), RAGE, and matrix metalloproteinase-9 (MMP-9). This study was designed to evaluate the effects of ergosterol on RAGE signaling in HSC-T6 cells. Ergosterol suppressed the activation of HSC-T6 cells induced by AGEs, and attenuated overexpressions of alpha-SMA, MMP-9, and epithelial-mesenchymal transition (EMT) markers, including N-cadherin and vimentin. We also found that these inhibitory effects of ergosterol on the activation of HSCs were dependent on peroxisome proliferator-activated receptor-gamma (PPARgamma) confirmed by PPARgamma reporter assay and PPARgamma knockdown. In addition, ergosterol also showed an inhibitory effect on the generation of AGEs, fructosamine, and α-dicarbonyl compounds in this study. Our results show that ergosterol can be used as a protective agent against hepatic fibrosis caused by induction of AGEs.