Sanghuangporus sanghuang extract inhibits the proliferation and invasion of lung cancer cells in vitro and in vivo.

BACKGROUND/OBJECTIVES: Sanghuangporus sanghuang (SS) has various medicinal effects, including anti-inflammation and anticancer activities. Despite the extensive research on SS, its molecular mechanisms of action on lung cancer are unclear. This study examined the impact of an SS alcohol extract (SAE) on lung cancer using in vitro and in vivo models. MATERIALS/METHODS: Different concentrations of SAE were used to culture lung cancer cells (A549 and H1650). A cell counting kit-8 assay was used to detect the survival ability of A549 and H1650 cells. A scratch assay and transwell cell invasion assay were used to detect the migration rate and invasive ability of SAE. Western blot analysis was used to detect the expression of B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), cyclin D1, cyclin-dependent kinases 4 (CDK4), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3). Lung cancer xenograft mice were used to detect the inhibiting ability of SAE in vivo. Hematoxylin and eosin staining and immunohistochemistry were used to detect the effect of SAE on the structural changes to the tumor and the expression of Bcl-2, Bax, cyclin D1, CDK4, STAT3, and p-STAT3 in lung cancer xenograft mice. RESULTS: SAE could inhibit lung cancer proliferation significantly in vitro and in vivo without cytotoxicity. SAE suppressed the viability, migration, and invasion of lung cancer cells in a dose and time-dependent manner. The SAE treatment significantly decreased the proapoptotic Bcl-2/Bax ratio and the expression of pro-proliferative proteins Cyclin D1 and CDK4 in vitro and in vivo. Furthermore, SAE also inhibited STAT3 expression. CONCLUSIONS: SAE reduced the cell viability and suppressed cell migration and invasion in human lung cancer cells. Moreover, SAE also exhibited anti-proliferation effects in vivo. Therefore, SAE may have benefits in cancer therapy.

Inoscavin A, a pyrone compound isolated from a Sanghuangporus vaninii extract, inhibits colon cancer cell growth and induces cell apoptosis via the hedgehog signaling pathway.

BACKGROUND: Sanghuangporus vaninii, a large precious medicinal fungus called Sanghuang in China, has significant antitumor activity. We previously reported that a Sanghuangporus vaninii extract could lead to apoptosis in HT-29 cells through the intrinsic apoptotic pathway. We further found that Inoscavin A exhibited anti-colon cancer activity, but its specific mechanisms have not been fully elucidated. METHODS: Inoscavin A was obtained from Sanghuangporus vaninii by the classic phytochemical separation technology. The male BALB/c nude mice were injected with HT-29 colon cancer cells as animal model. In order to observe the pathological changes of tumor section, the hematoxylin-eosin(H&E) staining was applied in the histological analysis. Metabolomics was utilized for the investigation of the overall changes of serum metabolites in animal model, and the potential targets of Inoscavin A were analyzed by Ingenuity Pathway Analysis (IPA). We further employed a molecular docking approach to predict the degree of combination of Inoscavin A and Smo. Then we further performed Western blotting and immunofluorescence analysis to investigate the expression of proteins involved in Hh-related pathways in tumor tissues. In addition, the colony formation assay, scratch-wound assay and transwell migration and invasion assay were conducted to evaluate the anti-colon-cancer activity of Inoscavin A. Concurrently, the mitochondrial membrane potential assay and TUNEL apoptosis assay were detected to demonstrate the effect of Inoscavin A on promoting HT-29 cells apoptosis. Western blot experiments verified the anti-tumor effects of Inoscavin A were modulated the protein expression of Shh, Ptch1, Smo and Gli1 in HT-29 cells. RESULTS: We showed that Inoscavin A, a pyrone compound isolated from the Sanghuangporus vaninii extract, exerted its antitumor activity in an HT-29 colon cancer cell xenograft mouse model. Subsequently, we first time prove that the antitumor effects of Inoscavin A were related to the hedgehog (Hh) signaling pathway. Furthermore, we demonstrated that Smo, the core receptor of the Hh pathway, was critical for the induction of apoptosis of Inoscavin A and that overexpression of this target could significantly rescue cell apoptosis induced by Inoscavin A treatment. CONCLUSION: Thus, our studies first propose that the natural outgrowth Inoscavin A exerted its anti-cancer effects by inhibiting Smo to suppress the activity of the Hh pathway though inhibiting cell proliferation and promoting apoptosis. These findings further indicate that Inoscavin A will be expected to be a prospective remedical compound for the treatment of colon cancer.

Insulinemic and Inflammatory Dietary Patterns and Risk of Prostate Cancer.

BACKGROUND: Hyperinsulinemia and inflammation are inter-related pathways that link diet with the risk of several chronic diseases. Evidence suggests that these pathways may also increase prostate cancer risk. OBJECTIVE: To determine whether hyperinsulinemic diet and inflammatory diet are associated with prostate cancer incidence and mortality. DESIGN, SETTING, AND PARTICIPANTS: We prospectively followed 41 209 men in the Health Professionals Follow-up Study (1986-2014). Scores for two validated dietary patterns were calculated from food frequency questionnaires at baseline and updated every 4 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Total, advanced, and lethal prostate cancer outcomes were assessed. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were determined for associations between two empirical hypothesis-oriented dietary patterns-empirical dietary index for hyperinsulinemia and empirical dietary inflammatory pattern-and prostate cancer risk estimated using Cox proportional hazard regression. RESULTS AND LIMITATIONS: During 28 yr of follow-up, 5929 incident cases of total prostate cancer, including 1019 advanced and 667 fatal, were documented. In multivariable-adjusted models, there was a 7% higher risk of advanced prostate cancer (HR: 1.07; 95% CI: 1.01-1.15) and a 9% higher risk of fatal prostate cancer (HR: 1.09; 95% CI: 1.00-1.18) per standard deviation (SD) increase in the hyperinsulinemic diet. When stratified by age, the hyperinsulinemic diet was associated with only earlier-onset aggressive prostate cancer (men under 65 yr), with per SD HRs of 1.20 (95% CI: 1.06-1.35) for advanced, 1.22 (1.04-1.42) for fatal, and 1.20 (1.04-1.38) for lethal. The inflammatory diet was not associated with prostate cancer risk in the overall study population, but was associated with earlier-onset lethal prostate cancer (per SD increase HR: 1.16; 95% CI: 1.00-1.35). CONCLUSIONS: Hyperinsulinemia and inflammation may be potential mechanisms linking dietary patterns with the risk of aggressive prostate cancer, particularly earlier-onset disease. PATIENT SUMMARY: Avoiding inflammatory and hyperinsulinemic dietary patterns may be beneficial for the prevention of clinically relevant prostate cancer, especially among younger men.

Association of dietary insulinemic potential and colorectal cancer risk in men and women.

Background: Insulin response may be important in colorectal cancer development. Diet modulates insulin response and may be a modifiable factor in colorectal cancer prevention. Objective: We examined associations between hyperinsulinemic diets and colorectal cancer risk with the use of an empirical dietary index for hyperinsulinemia (EDIH), a food-based index that characterizes dietary insulinemic potential on the basis of circulating C-peptide concentrations. Design: Diet was assessed every 4 y with food-frequency questionnaires in 46,210 men (Health Professionals Follow-Up Study, 1986-2012) and 74,191 women (Nurses' Health Study, 1984-2012) to calculate EDIH scores. Multivariable-adjusted Cox regression was used to calculate HRs and 95% CIs for colorectal, proximal/distal colon, and rectal cancer risk. Results: During 26 y of follow-up, we documented 2683 incident colorectal cancer cases. Comparing participants in the highest with those in the lowest quintiles, higher EDIH scores were associated with 33% (men: HR: 1.33; 95% CI: 1.11, 1.61; P-trend = 0.0005), 22% (women: HR: 1.22; 95% CI: 1.03, 1.45; P-trend = 0.01), and 26% (men and women: pooled HR: 1.26; 95% CI: 1.12, 1.42; P-trend <0.0001) higher risk of developing colorectal cancer. The positive associations were limited to the distal colon and rectum in men and to the distal and proximal colon in women; however, combined risk estimates were significant for all anatomic locations except for the rectum. For example, comparing participants in extreme EDIH quintiles, there was no significant association for proximal colon cancer in men (HR: 1.15; 95% CI: 0.84, 1.57; P-trend = 0.32), but the risk was elevated for distal colon (HR: 1.63; 95% CI: 1.14, 2.32; P-trend = 0.002) and rectal (HR: 1.63; 95% CI: 1.09, 2.44; P-trend = 0.01) cancer. Among women, the risk was elevated for proximal (HR: 1.28; 95% CI: 1.00, 1.63; P-trend = 0.03) and distal (HR: 1.46; 95% CI: 1.05, 2.03; P-trend = 0.03) colon cancer but not for rectal cancer (HR: 0.88; 95% CI: 0.60, 1.29; P-trend = 0.61). Conclusion: The findings suggest that the insulinemic potential of diet may partly underlie the influence of dietary intake on colorectal cancer development. This observational study was registered at www.clinicaltrials.gov as NCT03364582.

Association of Dietary Inflammatory Potential With Colorectal Cancer Risk in Men and Women.

IMPORTANCE: Inflammation is important in colorectal cancer development. Diet modulates inflammation and may thus be a crucial modifiable factor in colorectal cancer prevention. OBJECTIVE: To examine whether proinflammatory diets are associated with increased colorectal cancer risk by using an empirical dietary inflammatory pattern (EDIP) score based on a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating levels of inflammation biomarkers. DESIGN, SETTINGS, AND PARTICIPANTS: Cohort study of 46 804 men (Health Professionals Follow-up Study: 1986-2012) and 74 246 women (Nurses' Health Study: 1984-2012) followed for 26 years to examine associations between EDIP scores and colorectal cancer risk using Cox regression. We also examined associations in categories of alcohol intake and body weight. Data analysis began January 17, 2017, and was completed August 9, 2017. EXPOSURES: EDIP scores calculated from food frequency questionnaires administered every 4 years. MAIN OUTCOMES AND MEASURES: Incident colorectal cancer. RESULTS: We documented 2699 incident colorectal cancer cases over 2 571 831 person-years of follow-up. Compared with participants in the lowest EDIP quintile (Q) who had a colorectal cancer incidence rate (per 100 000 person-years) of 113 (men) and 80 (women), those in the highest Q had an incidence rate of 151 (men) and 92 (women), leading to an unadjusted rate difference of 38 and 12 more colorectal cancer cases, respectively, among those consuming highly proinflammatory diets. Comparing participants in the highest vs lowest EDIP Qs in multivariable-adjusted analyses, higher EDIP scores were associated with 44% (men: hazard ratio [HR], 1.44; 95% CI, 1.19-1.74; P < .001 for trend), 22% (women: HR, 1.22; 95% CI, 1.02-1.45; P = .007 for trend), and 32% (men and women: pooled HR, 1.32; 95% CI, 1.12-1.55; P < .001 for trend) higher risk of developing colorectal cancer. In both men and women, associations were observed in all anatomic subsites except for the rectum in women. In subgroups (P ≤ .02 for all interactions), associations differed by alcohol intake level, with stronger associations among men (Q5 vs Q1 HR, 1.62; 95% CI, 1.05-2.49; P = .002 for trend) and women (Q5 vs Q1 HR, 1.33; 95% CI, 0.97-1.81; P = .03 for trend) not consuming alcohol; and by body weight, with stronger associations among overweight/obese men (Q5 vs Q1 HR, 1.48; 95% CI, 1.12-1.94; P = .008 for trend) and lean women (Q5 vs Q1 HR, 1.31; 95% CI, 0.99-1.74; P = .01 for trend). CONCLUSIONS AND RELEVANCE: Findings suggest that inflammation is a potential mechanism linking dietary patterns and colorectal cancer development. Interventions to reduce the adverse role of proinflammatory diets may be more effective among overweight/obese men and lean women or men and women who do not consume alcohol.

Association of the Insulinemic Potential of Diet and Lifestyle With Risk of Digestive System Cancers in Men and Women.

BACKGROUND: We examined the role of the insulinemic potential of diet and lifestyle in the development of cancers of the digestive system, using two plasma C-peptide-based indices: the empirical dietary index for hyperinsulinemia (EDIH) and empirical lifestyle index for hyperinsulinemia (ELIH). METHODS: We used Cox regression to analyze data on 45 816 men (Health Professionals Follow-up Study, 1986-2012) and 74 191 women (Nurses' Health Study, 1984-2012) to examine associations between EDIH and ELIH scores and digestive system cancers. We computed the diet-only score (EDIH) from food-frequency questionnaires administered every 4 years. The lifestyle score (ELIH) included diet, body mass index, and physical activity. Outcomes included incident cancer of the digestive system (mouth, throat, esophagus, stomach, small intestine, and colorectum) and its accessory organs (pancreas, gallbladder, and liver). P values were two-sided. RESULTS: We found direct associations between higher insulinemic potential of diet or lifestyle and risk of developing digestive system cancers in both men and women. The pooled multivariable hazard ratios (HRs) for participants comparing the highest to lowest EDIH quintile were: HR = 1.27, 95% confidence interval (CI) = 1.15 to 1.40, P trend < .001 for digestive system cancers; HR = 1.30, 95% CI = 1.17 to 1.45, P trend < .001 for digestive tract cancers (excluding accessory organs); and HR = 1.15, 95% CI = 0.93 to 1.41, P trend = .48 for digestive accessory organ cancers. The same associations were stronger with the lifestyle score: HR = 1.47, 95% CI = 1.23 to 1.76, P trend < .001 for digestive system cancers; HR = 1.49, 95% CI = 1.14 to 1.95, P trend = .001 for digestive tract cancers; and HR = 1.43, 95% CI = 1.17 to 1.73, P trend < .001 for digestive accessory organ cancers. CONCLUSIONS: The findings suggest that interventions to reduce the insulinemic potential of diet and lifestyle may be a means of preventing digestive system cancer.

Nut consumption and prostate cancer risk and mortality.

BACKGROUND: Little is known of the association between nut consumption, and prostate cancer (PCa) incidence and survivorship. METHODS: We conducted an incidence analysis and a case-only survival analysis in the Health Professionals Follow-up Study on the associations of nut consumption (updated every 4 years) with PCa diagnosis, and PCa-specific and overall mortality. RESULTS: In 26 years, 6810 incident PCa cases were identified from 47 299 men. There was no association between nut consumption and being diagnosed with PCa or PCa-specific mortality. However, patients who consumed nuts five or more times per week after diagnosis had a significant 34% lower rate of overall mortality than those who consumed nuts less than once per month (HR=0.66, 95% CI: 0.52-0.83, P-trend=0.0005). CONCLUSIONS: There were no statistically significant associations between nut consumption, and PCa incidence or PCa-specific mortality. Frequent nut consumption after diagnosis was associated with significantly reduced overall mortality.

Night shift work at specific age ranges and chronic disease risk factors.

OBJECTIVES: We examined the association of night shift work history and age when night shift work was performed with cancer and cardiovascular disease risk factors among 54 724 women in the Nurses' Health Study (NHS) II. METHODS: We calculated age-adjusted and socioeconomic status-adjusted means and percentages for cancer and cardiovascular risk factors in 2009 across categories of night shift work history. We used multivariable-adjusted logistic regression to estimate odds ratios (ORs) and 95% CIs for key risk factors among 54 724 participants (72% ever shift workers). We further examined these associations by age (20-25, 26-35, 36-45 and 46+ years) at which shift work was performed. RESULTS: Ever night shift workers had increased odds of obesity (body mass index ≥30 kg/m(2); OR=1.37, 95% CI 1.31 to 1.43); higher caffeine intake (≥131 mg/day; OR=1.16, 95% CI 1.12 to 1.22) and total calorie intake (≥1715 kcal/day; OR=1.09, 95% CI 1.04 to 1.13); current smoking (OR=1.30, 95% CI 1.19 to 1.42); and shorter sleep durations (≤7 h of sleep/day; OR=1.19, 95% CI 1.15 to 1.24) compared to never night shift workers. These estimates varied depending on age at which night work was performed, with a suggestion that night shift work before age 25 was associated with fewer risk factors compared to night shift work at older ages. CONCLUSIONS: Our results indicate that night shift work may contribute to an adverse chronic disease risk profile, and that risk factors may vary depending on the age at which night shift work was performed.