CURCUMIN INCREASES THE SENSITIVITY OF BREAST CANCER CELLS TO TAMOXIFEN BY INHIBITING MRP2 MRNA EXPRESSION OF EFFLUX TRANSPORTER MRP2

Objective: Tamoxifen is the drug of choice to treat breast cancer positive for estrogen receptor. Long-term use of tamoxifen can induce multidrug resistance (MDR) associated with decreased sensitivity of cancer cells to the drug. One of the causes of MDR is overexpression of efflux transporter multidrug resistance-associated protein (MRP)2. Various drugs are known to act as MRP2 inhibitors, including curcumin. This study investigated the effects of curcumin on the sensitivity of breast cancer cells to tamoxifen through inhibition of MRP2. Methods: We used MCF-7 cells that were previously exposed to long-term tamoxifen treatment [MCF-7(T) cells]. MCF-7(T) cells were treated with 1 µM tamoxifen, curcumin (5, 10, and 20 µM), combinations of curcumin (5, 10, and 20 µM) and 1 µM tamoxifen, or 10 µM nevirapine (a known MRP2 inhibitor) for 5 d. Then, the cells were harvested, counted to assess cell viability, and evaluated for MRP2 mRNA expression. Results: Treatment with curcumin alone or in combination with tamoxifen significantly reduced cell viability at all curcumin concentrations compared with the control. The reduction in cell viability was accompanied by a reduced level of MRP2 mRNA expression. Conclusion: Application of curcumin to MCF-7 cells previously exposed to long-term tamoxifen treatment increase the sensitivity of cancer cells to tamoxifen. The increased sensitivity of these cells was attributed, at least in part, to inhibition of the efflux transporter MRP2

Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells

Tamoxifen is the first line drug used in the treatment of estrogen receptor-positive (ER+) breast cancer. The development of multidrug resistance (MDR) to tamoxifen remains a major challenge in the treatment of cancer. One of the mechanisms related to MDR is decrease of drug influx via overexpression of drug efflux transporters such as P-glycoprotein (P-gp/MDR1), multidrug resistance associated protein (MRP), or BCRP (breast cancer resistance protein). We aimed to investigate whether the sensitivity of tamoxifen to the cells is maintained through the short period and whether the expressions of several drug efflux transporters have been upregulated. We exposed MCF7 breast cancer cells with tamoxifen 1 μM for 10 passages (MCF7 (T)). The result showed that MCF7 began to lose their sensitivity to tamoxifen from the second passage. MCF7 (T) also showed a significant increase in all transporters examined compared with MCF7 parent cells. The result also showed a significant increase of CC50 in MCF7 (T) compared to that in MCF7 (97.54 μM and 3.04 μM, resp.). In conclusion, we suggest that the expression of several drug efflux transporters such as P-glycoprotein, MRP2, and BCRP might be used and further studied as a marker in the development of tamoxifen resistance

POTENTIAL HOLISTIC PREVENTIVE AND THERAPEUTIC EFFECTS OF GARCINIA MANGOSTANA EXTRACT OR ISOLATES IN TYPE 2 DIABETES MELLITUS: A REVIEW

Objective: The need for long-term medication in diabetes mellitus has led to a search for herbal medicines as alternative treatments. Several studies have shown that extract or isolates of Garcinia mangostana can help prevent and treat type 2 diabetes mellitus (T2DM). Methods: This review was conducted by searching various databases, including PubMed, ClinicalKey, ScienceDirect, and EBSCOhost. We analyzed papers published within the previous 10 y. Results: All in vitro, in vivo, and clinical studies that evaluated the pharmacological effects of extract or isolates of G. mangostana in T2DM were reviewed. G. mangostana was found to suppress adipogenesis and regulate lipid homeostasis, thus improving lipid profiles and preventing T2DM. G. mangostana also demonstrated hypoglycemic properties, including the ability to decrease fasting blood glucose and mildly increase pancreatic β-cell numbers and activity. The mangosteen-treated group in one study showed a decrease in Homeostatic Model Assesment for Insulin Resistance (HOMA-IR), indicating improved insulin sensitivity, along with a significant decrease in the high-sensitivity CRP (hs-CRP) levels. Histopathology showed that the α-mangostin-treated group had less damage to pancreatic β cells, healthier hepatocytes and central veins, and less glomerular and tubular epithelial necrosis than the diabetic control group. Moreover, the antioxidant effect of G. mangostana was shown to protect against the micro-and macrovascular damage caused by T2DM. Conclusion: Extract or isolates of G. mangostana possess strong potential to prevent and treat T2DM. Further research evaluating long-term outcome biomarkers in humans is needed to confirm the drug’s glycemic control capacity

THE ROLE OF ACALYPHA INDICA LINN. EXTRACT ON HEART RATES WITH MYASTHENIA GRAVIS RAT MODEL

  Objective: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. Acetylcholine is also used as a neurotransmitter in the autonomic nervous system. Striated cardiac muscle can be a target for immune attack manifesting as heart failure, arrhythmia, and sudden death. Involvement of the heart rate (HR) has been claimed and reported, but a causal connection between MG and altered cardiac function has not been found.Methods: For this study of experimental autoimmune MG (EAMG) is used rocuronium, prostigmine, and Acalypha indica (AI) Linn. compared with HR.Results: From the results, the study found that sympathetic activity of HR variability in EAMG injected with rocuronium 10 mg/kg body weight (BW) in 10 min significantly found increasing in measures of short-term variations in HR variability, indicating parasympathetic impairment.Conclusion: We conclude that in MG, cholinergic transmission is affected more diffusely than previously thought. Furthermore, AI was given orally 30 mg/kg BW has an effect similar to the injecting of prostigmine 10 mg/kg BW that can reduce HR. Driven by the fact that the pharmacological treatment of MG is unsatisfied, it needs the therapeutic development for MG using herbal ingredients of AI. This means that the AI compositions containing anti-MG whose composition should be investigated for the next research

Vitamin D supplementation alleviates insulin resistance in prediabetic rats by modifying IRS-1 and PPARγ/NF-κB expressions

BackgroundPrediabetes is a condition of intermediate hyperglycemia that may progress to type 2 diabetes. Vitamin D deficiency has been frequently linked to insulin resistance and diabetes. The study aimed to investigate the role of D supplementation and its possible mechanism of action on insulin resistance in prediabetic rats.MethodThe study was conducted on 24 male Wistar rats that were randomly divided into 6 rats as healthy controls and 18 prediabetic rats. Prediabetic rats were induced with a high-fat and high-glucose diet (HFD-G) combined with a low dose of streptozotocin. Rats with the prediabetic condition were then randomized into three groups of 12-week treatment: one group that received no treatment, one that received vitamin D3 at 100 IU/kg BW, and one group that received vitamin D3 at 1000 IU/kg BW. The high-fat and high-glucose diets were continuously given throughout the twelve weeks of treatment. At the end of the supplementation period, glucose control parameters, inflammatory markers, and the expressions of IRS1, PPARγ, NF-κB, and IRS1 were measured.ResultsVitamin D3 dose-dependently improves glucose control parameters, as shown by the reduction of fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycated albumin, insulin levels, and markers of insulin resistance (HOMA-IR). Upon histological analysis, vitamin D supplementation resulted in a reduction of the islet of Langerhans degeneration. Vitamin D also enhanced the ratio of IL-6/IL-10, reduced IRS1 phosphorylation at Ser307, increased expression of PPAR gamma, and reduced phosphorylation of NF-KB p65 at Ser536.ConclusionVitamin D supplementation reduces insulin resistance in prediabetic rats. The reduction might be due to the effects of vitamin D on IRS, PPARγ, and NF-κB expression