Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells.

Thyroid cancer (TC) is the most common endocrine malignancy, and its global incidence has steadily increased over the past 15 years. TC is broadly divided into well-differentiated, poorly differentiated, and undifferentiated types, depending on the histological and clinical parameters. Thus far, there are no effective treatments for undifferentiated thyroid cancers or advanced and recurrent cancer. Therefore, the development of an effective therapeutic is urgently needed for such patients. Piperlongumine (PL) is a naturally occurring small molecule derived from long pepper; it is selectively toxic to cancer cells by generating reactive oxygen species (ROS). In this study, we demonstrate the potential anticancer activity of PL in four TC cell lines. For this purpose, we cultured TC cell lines and analyzed the following parameters: Cell viability, colony formation, cell cycle, apoptosis, and cellular ROS induction. PL modulated the cell cycle, induced apoptosis, and suppressed tumorigenesis in TC cell lines in a dose- and time-dependent manner through ROS induction. Meanwhile, an intrinsic caspase-dependent apoptosis pathway was observed in the TC cells under PL treatment. The activation of Erk and the suppression of the Akt/mTOR pathways through ROS induction were seen in cells treated with PL. PL-mediated apoptosis in TC cells was through the ROS-Akt pathway. Finally, the anticancer effect and safety of PL were also demonstrated in vivo. Our findings indicate that PL exhibits antitumor activity and has the potential for use as a chemotherapeutic agent against TC. This is the first study to show the sensitivity of TC cell lines to PL.

Recurrent tertiary hyperparathyroidism due to supernumerary parathyroid glands in a patient receiving long-term hemodialysis: a case report.

BACKGROUND: Renal hyperparathyroidism is a common complication of chronic kidney disease (CKD) or end-stage renal disease (ESRD) characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Rapid correction of severe and prolonged hyperparathyroidism by surgical parathyroidectomy in long-term hemodialysis patients occasionally causes hungry bone syndrome. These patients then exhibit severe and long-lasting secondary or tertiary hyperparathyroidism with high bone turnover. CASE PRESENTATION: We report a case of recurrent tertiary hyperparathyroidism after total parathyroidectomy due to supernumerary parathyroid gland in a patient with long-term hemodialysis. Supplementation with intravenous calcium, oral calcium, and vitamin D immediately after patient surgery helps to prevent and treat hungry bone syndrome. CONCLUSIONS: We should prompt a search for the supernumerary parathyroid glands in ESRD patients, who have recurrent or persistent hyperparathyroidism after total parathyroidectomy. ESRD patients are more likely to develop hungry bone syndrome after parathyroidectomy. Prevention and treatment of hungry bone syndrome may be required after ectopic parathyroidectomy in clinical practice.

Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXRα) and Pregnane X Receptor (PXR).

Liver X receptor (LXR) is a nuclear receptor that regulates various biological processes, including de novo lipogenesis, cholesterol metabolism, and inflammation. Selective inhibition of LXR may aid the treatment of nonalcoholic fatty liver disease (NAFLD). Sesamin is a naturally occurring lignan in many dietary plants and has a wide range of beneficial effects on metabolism. The mechanism underlying sesamin action especially on the regulation of LXR remains elusive. Reporter assays, mRNA and protein expression, and in silico modeling were used to identify sesamin as an antagonist of LXRα. Sesamin was applied to the hepatic HepaRG and intestinal LS174T cells and showed that it markedly ameliorated lipid accumulation in the HepaRG cells, by reducing LXRα transactivation, inhibiting the expression of downstream target genes. This effect was associated with the stimulation of AMP-activated protein kinase (AMPK) signaling pathway, followed by decreased T0901317-LXRα-induced expression of SREBP-1c and its downstream target genes. Mechanistically, sesamin reduced the recruitment of SRC-1 but enhanced that of SMILE to the SREBP-1c promoter region under T0901317 treatment. It regulated the transcriptional control exerted by LXRα by influencing its interaction with coregulators and thus decreased mRNA and protein levels of genes downstream of LXRα and reduced lipid accumulation in hepatic cells. Additionally, sesamin reduced valproate- and rifampin-induced LXRα and pregnane X receptor (PXR) transactivation. This was associated with reduced expression of target genes and decreased lipid accumulation. Thus, sesamin is an antagonist of LXRα and PXR and suggests that it may alleviate drug-induced lipogenesis via the suppression of LXRα and PXR signaling.

Konjac supplement alleviated hypercholesterolemia and hyperglycemia in type 2 diabetic subjects--a randomized double-blind trial.

OBJECTIVES: The present study was designed to evaluate effects of konjac glucomannan (KGM) supplement (3.6 g/day) for 28 days on blood lipid and glucose levels in hyperlipidemic type 2 diabetic patients and the possible mechanism for the reductions in blood lipid levels. METHODS: Twenty-two diabetic subjects (age 64.2 + 8.4 years, BMI 25.5 + 3.2 kg/m(2)) with elevated blood cholesterol levels (fasting glucose between 6.7-14.4 mmol/L), but currently not taking lipid-lowering medication, were recruited to participate in a two 28-day period, randomized, double-blind, crossover clinical trial. Fasting blood samples drawn on the initial and final days of each period were determined for plasma lipids and glucose levels. Feces collected at the end of each experimental period were analyzed for neutral sterol and bile acid contents. RESULTS: Compared with placebo, KGM effectively reduced plasma cholesterol (11.1%, p = 0.0001, adjusted alpha = 0.006), LDL-cholesterol (20.7%, p = 0.0004, adjusted alpha = 0.006), total/HDL cholesterol ratio (15.6%, p = 0.0005, adjusted alpha = 0.007), ApoB (12.9%, p = 0.0001, adjusted alpha = 0.006) and fasting glucose (23.2%, p = 0.002, adjusted alpha = 0.008). Plasma triglyceride, HDL-cholesterol, LDL/HDL cholesterol, postprandial glucose and body weight were not significant after adjustment by the Bonferroni-Hochberg procedure. Fecal neutral sterol and bile acid concentrations were increased by 18.0% (p = 0.004) and 75.4% (p < 0.001), respectively, with KGM supplement. CONCLUSIONS: The KGM supplement improved blood lipid levels by enhancing fecal excretion of neutral sterol and bile acid and alleviated the elevated glucose levels in diabetic subjects. KGM could be an adjunct for the treatment of hyperlipidemic diabetic subjects.