METHODS: The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1β, respectively.
RESULTS: LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1β. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation.
CONCLUSION: There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.
METHODS: Five groups of adult male rats were used in this experiment. Normal/control group; the rats were injected subcutaneously with 15 mg/kg of sterile normal saline once a week for two weeks, and orally administered with 10% Tween 20 (5 mL/kg). Carcinogen and treatment groups; the rats were injected subcutaneously each with 15 mg/kg body weight AOM once a week for 2 weeks and were continued to be fed for two months, respectively with 10% Tween 20, 500 and 250mg/kg body weight plant extracts. Reference group; the rats were injected subcutaneously with 15 mg/kg body weight AOM once a week for 2 weeks, and injected intraperitoneally with fluorouracil 35 mg/kg body weight for five consecutive days.
RESULT: Total ACF detected in methylene blue stained whole mounts of rat colon were 21, 23and 130 in rats fed with 500, 250 mg/kg body weight treatment and carcinogen groups, respectively. Treatment with high and low doses of the plant extract led to83.6% and 82.2% decrease in the total crypts in the groups fed 500 mg/kg and 250 mg/kg Gynura procumbens respectively compared to carcinogen group. Immunohistochemical staining of ACF showed suppressed azoxymethane induced colonic cell proliferation and Bcl-2 expression. Glutathione-S-transfarase and superoxide dismutase activities were higher in treated rats compared to carcinogen groups.
CONCLUSION: Gynura procumbens reduced the incidence of AOM induced ACF. The findings showed that Gynura procumbens may have antiproliferative and antioxidative properties. Moreover, Gynura procumbens possesses the medicinal properties to prevent colon cancer.
METHODS: We used multiple search strategies in MEDLINE through PubMed to seek for suitable articles that had case-control design with gastric cancer as outcome.
RESULTS: The outcomes of our study shows protection (odds ratio [OR] 0.55, P = 0.003) and susceptibility (OR 1.94, P = 0.0004), both significant with low and medium-high intake of capsaicin, respectively, although under relatively heterogeneous conditions (P(heterogeneity) = <0.0001). Outlier analysis resulted in loss of overall heterogeneity (P = 0.14) without affecting the pooled ORs. Among the subgroups, low intake elicited protection in both Korean (OR 0.37) and Mexican (OR 0.63) populations while high intake rendered these subgroups susceptible (OR 2.96 and OR 1.57, respectively). These subgroup values were highly significant (P = 0.0001-0.01) obtained in heterogeneous conditions (P(heterogeneity)
OBJECTIVE: The objective of this study is to study the chemoprevention effects of MEMCL against azoxymethane (AOM)-induced colon cancer and to examine the involvement of endogenous antioxidants Materials and methods: Male Sprague-Dawley rats, divided into five groups (n = 7), were injected intraperitoneally once weekly for 2 weeks with 15 mg/kg AOM, except for the normal group (received saline). The animals were then administered orally for 8 weeks with 8% Tween-80 (vehicle; normal group), 8% Tween-80 (vehicle; cancer group) or, 50, 250 or 500 mg/kg MEMC. After treatments, colon samples were collected from each rat for the histopathological analysis, quantification of aberrant crypt foci formed and determination of colon antioxidant levels. MEMC was also subjected to HPLC analysis.
RESULTS: The extract exerted significant (p
PURPOSE: The present study was designed to evaluate the anti-angiogenic and apoptosis induction properties of gramine through inhibiting TGF-β on DMBA induced oral squamous cell carcinoma (OSCC) in the hamster buccal pouch (HBP).
METHODS: The effects of gramine on TGF-β signalling in DMBA induced carcinogenic events such as angiogenesis and apoptosis were analysed by studying the mRNA expression using RT-PCR, protein expression by western blot and histopathological analysis using haematoxylin and eosin (H & E) staining.
RESULTS: Gramine significantly inhibited phosphorylation and nuclear translocation of Smad2 and Smad4 by blocking activity of the TGFβ-RII, RI and activation of inhibitory Smad7. Gramine inhibited angiogenic markers such as MMP-2, MMP-9, HIF-1α, VEGF, and VEGF-R2 as well as increased TIMP-2 expression. Furthermore, gramine induced apoptosis in DMBA induced tumour bearing animals by up regulating the pro apoptotic proteins Bax, cytochrome C, apaf-1, caspase-9 caspase-3 and PARP.
CONCLUSION: In this study, we clearly demonstrated that gramine treatment diminishes angiogenesis and induces apoptosis in hamster buccal pouch (HBP) carcinogenesis by modulating TGF-β signals.