Neutralizing antibody to proNGF rescues erectile function by regulating the expression of neurotrophic and angiogenic factors in a mouse model of cavernous nerve injury.

BACKGROUND: Radical prostatectomy induces some degree of cavernous nerve injury (CNI) and causes denervation-induced pathologic changes in cavernous vasculature, regardless of the advances in surgical techniques and robotic procedures. The precursor for nerve growth factor (proNGF) is known to be involved in neuronal cell apoptosis and microvascular dysfunction through its receptor p75NTR . OBJECTIVES: To determine the expression of proNGF/p75NTR and the efficacy of proNGF neutralizing antibody (anti-proNGF-Ab) in a mouse model of ED induced by CNI. MATERIALS AND METHODS: Age-matched 12-week-old C57BL/6 mice were distributed into three groups: sham group and bilateral CNI group treated with intracavernous injections of PBS (20 µL) or of anti-proNGF-Ab (20 µg in 20 µL of PBS) on days -3 and 0. Two weeks after treatment, erectile function was measured by electrical stimulation of cavernous nerve. Penis tissues from a separate group of animals were harvested for further analysis. We also determined the efficacy of anti-proNGF-Ab on neural preservation in major pelvic ganglion (MPG) ex vivo. RESULTS: We observed increased penile expression of proNGF and p75NTR after CNI. Intracavernous administration of anti-proNGF-Ab increased nNOS and neurofilament expression probably by enhancing the production of neurotrophic factors, such as neurotrophin-3, NGF, and brain-derived neurotrophic factor. Anti-proNGF-Ab preserved the integrity of cavernous sinusoids, such as pericytes, endothelial cells, and endothelial cell-to-cell junctions, possibly by controlling angiogenic factors (angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor) and induced endogenous eNOS phosphorylation in CNI mice. And finally, treatment with anti-proNGF-Ab rescued erectile function in CNI mice. Anti-proNGF-Ab also enhanced neurite sprouting from MPG exposed to lipopolysaccharide. DISCUSSION AND CONCLUSION: The preservation of damaged cavernous neurovasculature through inhibition of the proNGF/p75NTR pathway may be a novel strategy to treat radical prostatectomy-induced erectile dysfunction.

Artemisiae Iwayomogii Herba Inhibits Growth, Motility, and the PI3K/AKT/mTOR Signaling Pathway in Hepatocellular Carcinoma Cells.

Artemisia gmelinii (Artemisia iwayomogi) has been used in traditional medicine to cure various infectious diseases such as cholecystitis, hepatitis, and jaundice. In this study, the Artemisiae Iwayomogii Herba ethanol extract was investigated for the ability to inhibit growth of hepatocellular carcinoma and its underlying mechanism involved. The antiproliferative effect of Artemisiae Iwayomogii Herba ethanol extract was evaluated using cell viability and proliferation assays. The effect of Artemisiae Iwayomogii Herba ethanol extract on apoptosis was measured using western blotting, terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling staining, JC-1 staining, cytochrome c release, immunohistochemistry, and immunofluorescence in ex vivo mouse xenografts. Artemisiae Iwayomogii Herba ethanol extract inhibited hepatocellular carcinoma cell growth and proliferation in a dose-dependent manner. The apoptotic effect of Artemisiae Iwayomogii Herba ethanol extract was observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling-positive apoptotic cells. Artemisiae Iwayomogii Herba ethanol extract also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, Artemisiae Iwayomogii Herba ethanol extract inhibited hepatocellular carcinoma cell invasion and migration. In the ex vivo model, Artemisiae Iwayomogii Herba ethanol extract significantly inhibited tumor cell proliferation and increased the number of apoptotic cells with more activated cleaved caspase-3. A mechanistic study revealed that Artemisiae Iwayomogii Herba ethanol extract effectively suppressed the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma cells. Our findings demonstrate that Artemisiae Iwayomogii Herba ethanol extract can efficiently induce apoptosis and inhibit the growth, migration, and invasion of human hepatocellular carcinoma cells, and simultaneously block PI3K/AKT/mTOR pathway. We therefore suggest Artemisiae Iwayomogii Herba ethanol extract as a novel natural agent for prevention and therapy of hepatocellular carcinoma.

Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma.

Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. The XS-5 and XS-6 extracts dose-dependently inhibited the growth and proliferation in HCC cell lines. The apoptotic effects of them were observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling- (TUNEL-) positive apoptotic cells. They also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, they inhibited the invasion and migration of HCC cells. In an ex vivo model, the extracts significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of the cleaved caspase-3. A mechanistic study revealed that they effectively suppressed PI3K/AKT/mTOR signaling pathways in HCC cells. Taken together, our findings demonstrate that they could efficiently not only induce apoptosis but also inhibit cell growth, migration, and invasion of human HCC cells by blocking the PI3K/AKT/mTOR pathway. We suggest XS-5 and XS-6 as novel natural anti-HCC agents.

An ethyl acetate fraction of Artemisia capillaris (ACE-63) induced apoptosis and anti-angiogenesis via inhibition of PI3K/AKT signaling in hepatocellular carcinoma.

In cancer treatment, herbal medicines may be a good choice because of the reduced risk of adverse side effects. Artemisia capillaris has been recognized as a promising candidate due to its hepatoprotective effects. Herein, we investigated whether A. capillaris-derived fraction (ACE-63) could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. In this study, ACE-63 effectively inhibited the growth and proliferation of HCC cells. ACE-63 induced apoptosis, as observed using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, which was accompanied with increases in cleaved Poly (ADP-ribose) polymerase (PARP) and caspase-3 in HCC cells. Additionally, the pro-apoptotic effect of ACE-63 was demonstrated by a decrease in the expression of the X-linked inhibitor of apoptosis protein (XIAP) and survivin via a loss of mitochondrial membrane potential. In an ex vivo model, ACE-63 significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of cleaved caspase-3 and DNA fragmentation. In addition, ACE-63 decreased the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor and inhibited tube formation of human umbilical vein endothelial cells. A mechanistic study revealed that ACE-63 effectively suppressed the PI3K/AKT/mTOR signaling pathways, which were observed as a target signaling by phosphokinase array. Taken together, our findings demonstrate that ACE-63 could not only efficiently induce apoptosis but also inhibit the growth/angiogenesis of human HCC cells by blocking the PI3K/AKT/mTOR signaling pathway, suggesting that ACE-63 may be a new chemotherapeutic candidate against HCC.

Artemisia Capillaris leaves inhibit cell proliferation and induce apoptosis in hepatocellular carcinoma.

BACKGROUND: Natural product is one of the most important sources of drugs used in pharmaceutical therapeutics. Artemisia capillaris has been traditionally used as a hepatoprotective and anti-inflammatory agent. In this study, we extracted an ethanol fraction (LAC117) from the dried leaves of Artemisia capillaris and identified its anticancer activity and mechanism of action against hepatocellular carcinoma (HCC). METHODS: Anti-proliferative effect of LAC117 was evaluated by MTT assay and BrdU assay. The apoptotic effect of LAC117 on the expression of cleaved PARP and cleaved caspase-3 was evaluated by Western blot and immunohistochemistry from in vivo mouse xenograft, respectively. RESULTS: We found that LAC117 strongly suppressed the growth and proliferation of human HCC cell lines (HepG2 and Huh7). Induction of apoptosis was evidenced by the increases of cleaved caspase-3 and PARP as well as TUNEL-positive cells. Additionally, the pro-apoptotic effect of LAC117 was observed by a decrease in the expression of the XIAP and an increase in cytochrome c releases via mitochondrial membrane potential. Moreover, it significantly inhibited PI3K/AKT pathway in HCC in vivo and in vitro. LAC117 suppressed tumor growth in an ex vivo model as well as in vivo mouse xenograft by inducing apoptosis and inhibiting tumor cell proliferation. CONCLUSIONS: The present study highlights that LAC117 could not only efficiently induce apoptosis, but also inhibit the growth of human HCC cells by blocking the PI3K/AKT signaling pathway, suggesting that LAC117 would be a potentially useful drug candidate against HCC.

Artemisia capillaris extract AC68 induces apoptosis of hepatocellular carcinoma by blocking the PI3K/AKT pathway.

Artemisia capillaris Thunberg (AC) has been widely used to treat various diseases including hepatitis and is known to affect many cellular events such as cell proliferation and apoptosis. Herein a potent ethyl acetate fraction (AC68) was newly extracted from AC, and was assessed for its anti-cancer efficacy in progression and growth of hepatocellular carcinoma (HCC). AC68 dose-dependently inhibited the growth and proliferation of two HCC cell lines. The AC68-induced apoptosis was observed by increased levels of cleaved caspase-3 and decreased survivin, XIAP, and MCL-1 expression via mitochondria membrane potential change, as well as elevated numbers of TUNEL-positive apoptotic cells. AC68 was also found to suppress invasion and migration of HCC cells. Moreover, it inhibited PI3K/AKT signaling pathway in vitro and in vivo. In vivo study showed that AC68 significantly inhibited tumor growth in HCC mouse xenograft model, and induced apoptosis by increasing the expression of cleaved caspase-3. The expression of PCNA was decreased by the treatment of AC68. Taken together, our data demonstrated that AC68 not only induced apoptosis but also inhibited cell growth, migration, and invasion of liver cancer cells by blocking the PI3K/AKT pathway. We suggest that AC68 may be a potent chemotherapeutic candidate for the treatment of HCC.

Centella asiatica Leaf Extract Protects Against Indomethacin-Induced Gastric Mucosal Injury in Rats.

The present study evaluated the protective effect of Centella asiatica (gotu kola) leaf extract (CAE) against indomethacin (IND)-induced gastric mucosal injury in rats. Gastric mucosal injury was induced by the oral administration of IND to the rats after a 24 h fast. CAE (50 or 250 mg/kg) or lansoprazole (a reference drug) was orally administrated 30 min before the IND administration, and 5 h later, the stomachs were removed to quantify the lesions. Orally administered CAE significantly reduced IND-induced gastric injury. The histopathological observations (hematoxylin-eosin and Periodic acid-Schiff staining) confirmed the protection against gastric mucosal injury. Also, CAE decreased the malondialdehyde content compared to the control group. Moreover, pretreatment with CAE resulted in a significant reduction in the elevated expression of tumor necrosis factor, Cyclooxygenase (COX)-2, and inducible nitric oxide synthase. These results suggested that CAE possesses gastroprotective effects against IND-induced gastric mucosal injury, which could be attributed to its ability to inhibit lipid peroxidation and stimulate gastric mucus secretion in the rat gastric mucosa.

Antiangiogenic Activity of Acer tegmentosum Maxim Water Extract in Vitro and in Vivo.

Angiogenesis, the formation of new blood vessels, is critical for tumor growth and metastasis. Notably, tumors themselves can lead to angiogenesis by inducing vascular endothelial growth factor (VEGF), which is one of the most potent angiogenic factors. Inhibition of angiogenesis is currently perceived as one of the most promising strategies for the blockage of tumor growth. In this study, we investigated the effects of Acer tegmentosum maxim water extract (ATME) on angiogenesis and its underlying signal mechanism. We studied the antiangiogenic activity of ATME by using human umbilical vein endothelial cells (HUVECs). ATME strongly inhibited VEGF-induced endothelial cell proliferation, migration, invasion, and tube formation, as well as vessel sprouting in a rat aortic ring sprouting assay. Moreover, we found that the p44/42 mitogen activated protein (MAP) kinase signaling pathway is involved in the inhibition of angiogenesis by ATME. Moreover, when we performed the in vivo matrigel plug assay, VEGF-induced angiogenesis was potently reduced when compared to that for the control group. Taken together, these results suggest that ATME exhibits potent antiangiogenic activity in vivo and in vitro and that these effects are regulated by the extracellular regulated kinase (ERK) pathway.

CD-200 induces apoptosis and inhibits Bcr-Abl signaling in imatinib-resistant chronic myeloid leukemia with T315I mutation.

Chronic myeloid leukemia (CML) is characterized by a constitutively active Bcr-Abl tyrosine kinase. Although Imatinib has been proven to be an effective drug against CML, its resistance has been observed with disease relapse due to T315I predominant point mutation. Liriodendron tulipifera L., one of the fastest growing hardwood tree species, exerts antioxidant activity and anti-inflammatory effects. However, its anticancer effect has been minimally reported. In this study, we extracted CD-200 from Liriodendron tulipifera L. and investigated its effect on cell survival or apoptosis in CML cells with Bcr-Abl/T315I (BaF3/T315I) as well as wild-type Bcr-Abl (BaF3/WT). CD-200 inhibited cell proliferation in the BaF3/WT cells, and also in the BaF3/T315I cells with Imatinib resistance. Moreover, it strongly inhibited Bcr-Abl signaling pathways in a dose-dependent manner. Also, it significantly increased the sub-G1 phase and the expression of cleaved PARP and caspase-3, as well as the TUNEL-positive apoptotic cells. In addition, we observed that CD-200 induced apoptosis with a loss of mitochondrial membrane potential by decreasing the expression of Mcl-1 and survivin. Furthermore, CD-200 showed a significant inhibition in tumor growth, compared to Imatinib in BaF3/T315I mouse xenograft models. Taken together, our study demonstrates that CD-200 exhibits apoptosis induction and anti-proliferative effect by blocking the Bcr-Abl signaling pathways in the Bcr-Abl/T315I with resistance to Imatinib. We suggest that CD-200 may be a natural product to target Bcr-Abl and overcome Imatinib resistance in CML patients.

SB365, Pulsatilla saponin D, suppresses the growth of gefitinib-resistant NSCLC cells with Met amplification.

Clinical treatment using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib or erlotinib has been applied in patients with non-small cell lung cancers (NSCLCs). Unfortunately, acquired drug resistance emerges in these patients due to the amplification of the Met proto-oncogene, which may be a compensatory mechanism of NSCLCs against EGFR inhibition. To overcome this resistance, identification of new small-molecule natural compounds is crucial for cancer therapeutics. In this regard, SB365, saponin D from the root of Pulsatilla koreana which has been used as a traditional medicine in Korea for several diseases, has attracted wide interest. In the present study, SB365 effectively suppressed the proliferation of gefitinib-resistant HCC827GR NSCLC cells with Met amplification. Notably, our data revealed that SB365 inhibited the phosphorylation of Met and the downstream signaling pathway required for growth and survival in the Met-amplified HCC827GR cells. Moreover, SB365 suppressed the anchorage-independent growth, migration and invasion along with induction of apoptosis in the HCC827GR cells. Therefore, these results suggest that SB365 is good candidate as a natural product for use in the treatment of Met-amplified NSCLCs.

20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. High mortality from HCC is mainly due to widespread prevalence and the lack of effective treatment, since systemic chemotherapy is ineffective, while the targeted agent Sorafenib extends median survival only briefly. The steroidal saponin 20(S)-ginsenoside Rg3 from Panax ginseng C.A. Meyer is proposed to chemosensitize to various therapeutic drugs through an unknown mechanism. Since autophagy often serves as cell survival mechanism in cancer cells exposed to chemotherapeutic agents, we examined the ability of Rg3 to inhibit autophagy and chemosensitize HCC cell lines to doxorubicin in vitro. We show that Rg3 inhibits late stage autophagy, possibly through changes in gene expression. Doxorubicin-induced autophagy plays a protective role in HCC cells, and therefore Rg3 treatment synergizes with doxorubicin to kill HCC cell lines, but the combination is relatively nontoxic in normal liver cells. In addition, Rg3 was well-tolerated in mice and synergized with doxorubicin to inhibit tumor growth in HCC xenografts in vivo. Since novel in vivo inhibitors of autophagy are desirable for clinical use, we propose that Rg3 is such a compound, and that combination therapy with classical chemotherapeutic drugs may represent an effective therapeutic strategy for HCC treatment.

SB365, Pulsatilla saponin D suppresses proliferation and induces apoptosis of pancreatic cancer cells.

Pulsatilla koreana has been used as a traditional medicine for the treatment of various diseases. The purpose of this study was to determine whether SB365, Pulsatilla saponin D isolated from the root of Pulsatilla koreana inhibits the progression of pancreatic cancer. We found that SB365 strongly suppressed the growth and proliferation of 5 human pancreatic cancer cell lines (MIAPaCa-2, BXPC-3, PANC-1, AsPC-1 and HPAC). The apoptotic effect of SB365 was demonstrated by increased levels of cleaved caspase-3 and decreased Bcl-2 expression via mitochondrial membrane potential, as well as elevated numbers of terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells. SB365 was also found to exert an anti-angiogenic effect by decreasing the expression of HIF-1α and VEGF, major factors of angiogenesis, which was confirmed by the suppression of tumor sphere formation of pancreatic cancer cells. An in vivo mouse xenograft study showed that SB365 significantly inhibited tumor growth through the induction of apoptosis and inhibition of angiogenesis with strong anticancer activity. Therefore, SB365 is a good candidate as a natural product for use in the treatment of pancreatic cancer.

A formulated red ginseng extract upregulates CHOP and increases TRAIL-mediated cytotoxicity in human hepatocellular carcinoma cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent because its cytotoxicity is selective for tumor cells. Despite promising outcomes in clinical trials using this ligand, sustained clinical responses have been impeded because cancer cells acquire resistance to TRAIL-based therapies. Ginseng, a well-known food product consumed globally, has been reported to reduce fatigue and possess antioxidant and antitumor activities. We explored the sensitizing influence of a formulated red ginseng extract (RGE) on TRAIL-derived cell death in hepatocellular carcinoma (HCC) cell lines and the underlying molecular mechanisms responsible for TRAIL sensitization. We found that the RGE promoted TRAIL-derived apoptosis in HepG2, Huh-7 and Hep3B cell lines. We also found that death receptor 5 expression was induced by the RGE and mediated by C/EBP homologous protein (CHOP). shRNA-induced downregulation of CHOP expression effectively suppressed cell death induced by combined treatment with the RGE and TRAIL in the HepG2 cell line, indicating that RGE-related upregulation of the CHOP protein plays an important role in sensitizing TRAIL-derived apoptosis. In summary, we showed that the RGE sensitized human HCC cell lines to TRAIL-derived cell death and could be utilized as a dietary supplement in combination with cancer treatment.

SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway.

Pulsatilla koreana has been used as a traditional medicine for the treatment of several diseases. The purpose of this study was to determine if SB365, Pulsatilla saponin D isolated from the root of P. koreana inhibits the progression of colon cancer. We found that SB365 strongly suppressed the growth and proliferation of colon cancer cells and induced their apoptosis. Also, SB365 showed anti-angiogenic activity by decreasing the expression of HIF-1α and VEGF. These results were confirmed by an in vivo study showing that SB365 significantly inhibited tumor growth by the induction of apoptosis and inhibition of angiogenesis with stronger anticancer activity than 5-FU. When further examined for its anticancer mechanism, SB365 effectively suppressed the AKT/mTOR pathway both in vitro and in vivo. Taken together, our study demonstrated that SB365 inhibits the AKT/mTOR pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis. Therefore, SB365 is a good candidate as a natural product for use in the treatment of colon cancer.

Antitumor activity of Pulsatilla koreana extract in anaplastic thyroid cancer via apoptosis and anti-angiogenesis.

Plants or herb extracts have emerged as a novel approach to controling various diseases, including cancers. Among them, Pulsatilla koreana extract (PKE) has been widely used as an anti-inflammatory agent and for treating dysentery in traditional Korean and Chinese medicine. However, the effect of PKE as a cancer drug candidate has been less reported. Thus, we investigated the effect of PKE on cell growth and its mechanism in anaplastic thyroid cancer (ATC) cells. In this study, PKE suppressed the growth of ATC cells in a dose-dependent manner. Additionally, PKE induced apoptosis by increasing expression of cleaved PARP and caspase-3 in ATC cells. The apoptotic effect of PKE was confirmed by diamidino-2-phenylindole (DAPI) and terminal deoxynucleotidyltransferase-mediated nick end labeling (TUNEL) assay, showing apoptotic body and DNA fragmentation. In addition, PKE decreased the expression of hypoxia-inducible factor 1α (HIF­1α) and vascular endothelial growth factor (VEGF) as well as inhibiting tube formation and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, in vivo studies showed that PKE significantly inhibited tumor growth and weight in a mouse xenograft model. Taken together, the present study demonstrated that PKE induced apoptosis, as well as inhibiting cell growth and angiogenesis in ATC cells. We suggest that PKE is a potent anticancer drug candidate for the treatment of thyroid cancer.

In-vitro cell tests using doxorubicin-loaded polymeric TiO2 nanotubes used for cancer photothermotherapy.

To determine the appropriate surfactant to be added to TiO(2) nanotubes (TNTs) for use in cancer photothermotherapy, this study measured the increase in temperature and examined the size distribution of TNT particles loaded with different surfactants during near-infrared irradiation. In addition, in-vitro cell (fluorescein isothiocyanate and MTT assay) tests were carried out to examine the cytotoxic effect of doxorubicin-loaded and polyvinyl alcohol-added TNTs (pTNTs). The mean particle size of the pTNTs was 151.8 nm with a particle size variation of less than 3 nm, which is low enough to flow through blood vessels without causing a blockage. The temperature of the pTNTs was ∼47°C, which is high enough to destroy cancer cells. Doxorubicin-loaded TNTs and pTNTs in combination with a near-infrared laser showed a cell viability of 4.5% - a sufficiently high cytotoxic effect.

Comparison of oxidized porous silicon with bare porous silicon as a photothermal agent for cancer cell destruction based on in vitro cell test results.

In the systematic administration of cancer, cancer markers are normally used to help the therapeutic agents access the cancer cells spontaneously. Therefore, it is essential to functionalize the surface of porous silicon (pSi) for cancer markers to attach well to pSi in systematic administration because most cancer markers does not attach easily to pSi. The thermal oxidation of pSi is adopted most widely as a surface functionalization technique for pSi. This study examined the photothermal properties and cancer cell-killing ability of oxidized pSi (pSiO). The temperature measurement and in vitro cell tests including the annexin V-fluorescein isothiocyanate (FITC) apoptosis assay tests, MTT assay tests, and Trypan blue cell death assay tests were performed to compare the photothermal properties and the cytotoxic effect of pSiO with those of pSi in combination with an 808-nm NIR laser. pSiO showed lower photothermal properties and a lower cell-death rate than bare pSi. On the other hand, the pSiO treatment used in combination with an NIR laser treatment showed a cytotoxic effect high enough to kill a considerable portion of the cancer cells.

Apoptotic and anti-angiogenic effects of Pulsatilla koreana extract on hepatocellular carcinoma.

Chemoprevention through the use of food and plants has emerged as a novel approach to control various malignancies including cancer. Pulsatilla koreana extract (PKE) has been used to treat malaria and dysentery. The functions and effect of PKE in cancer treatment have been reported but with less information. In this study, we investigated the effect of PKE on the progression of hepatocellular carcinoma (HCC) cells and its mechanism. PKE strongly suppressed the growth of HCC cells in a dose-dependent manner. Apoptosis by PKE was observed by DAPI and TUNEL staining and accompanied with increases of cleaved PARP and caspase-3 in Huh-7 cells. Also, PKE decreased the expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF), and inhibited tube formation and migration of human umbilical vein endothelial cells (HUVECs). In addition, PKE potently suppressed in vivo neovascularization in a mouse Matrigel plug assay. Furthermore, in vivo study showed that PKE significantly inhibited tumor growth in a mouse xenograft model, and induced apoptosis by increasing the cleaved PARP and caspase-3. The expressions of Ki-67, VEGF, and CD31 in the tumor tissue were decreased by the treatment of PKE. Taken together, our study demonstrates that PKE not only induced apoptosis but also inhibited cell growth and angiogenesis of human HCC. We suggest that PKE is an effective chemotherapeutic candidate for cancer therapy against HCC.

[Preclinical experience in stem cell therapy for digestive tract diseases].

Adult stem cells are multipotent and self-renewing cells that contain several functions; i) migration and homing potential: stem cells can migrate to injured and inflamed tissues. ii) differentiation potential: stem cells which migrated to injured tissues can be differentiated into multiple cell types for repairing and regenerating the tissues. iii) immunomodulatory properties: stem cells, especially mesenchymal stem cells can suppress immune system such as inflammation. All those characteristics might be useful for the treatment of the digestive tract diseases which are complex and encompass a broad spectrum of different pathogenesis. Preclinical stem cell therapy showed some promising results, especially in liver failure, pancreatitis, sepsis, and inflammatory bowel disease. If we can understand more about the mechanism of stem cell action, stem cell therapy can become a promising alternative treatment for refractory digestive disease in the near future. In this review, we summarized current preclinical experiences in diseases of the digestive tract using stem cells. (Korean J Gastroenterol 2011;58:133-138).

In-vivo cancer cell destruction using porous silicon nanoparticles.

In-vivo animal tests were performed to investigate the feasibility of photothermal therapy based on porous silicon nanoparticles (PSiNPs) in combination with a near-infrared (NIR) laser. The in-vivo animal test results showed that the murine colon carcinoma (CT-26) tumors were completely resorbed with minimal damage to surrounding healthy tissue within 5 days after PSiNPs and NIR laser treatments. In contrast, tumors in the groups treated only with PSiNPs or NIR and a control group continued to grow until the mice died. All of the mice treated with both PSiNPs and NIR remained healthy and free of tumors even 90 days after the treatment. In-vivo fluorescence imaging and the urine and feces tests revealed that PSiNPs injected intratumorally into mice were cleared mainly through the urine. The in-vivo animal test results suggest that thermotherapy based on porous silicon in combination with NIR laser irradiation can efficiently destroy cancer cells selectively without damaging the surrounding healthy cells.