Sulforaphene and sulforaphane in commonly consumed cruciferous plants contributed to antiproliferation in HCT116 colon cancer cells

AbstractObjectiveTo analyze two isothiocyanates (sulforaphene and sulforaphane) and their antiproliferative effect of 11 indigenous cruciferous vegetables.MethodsPhytoconstituents identification was conducted by high performance liquid chromatography and gas chromatography-mass spectrometer techniques. The antiproliferation was evaluated in colon cancer cell line HCT116 by MTT assay.ResultsIsothiocyanate identification by high performance liquid chromatography showed that broccoli, cabbage, “Khi-Hood” (Raphanus sativus L. var. caudatus Alef) and Chinese radish contained isothiocyanates sulforaphane. Sulforaphene and sulforaphane in broccoli, cabbage and “Khi-Hood” were characterized by the gas chromatography-mass spectrometer analysis. Antiproliferation screening by MTT assay found that the potent plants which possessed IC50 below 50 μg/mL were cabbage and “Khi-Hood”, while the others had low antiproliferation with IC50 higher than 50 μg/mL. Difference in antiproliferation was probably due to difference existed phytochemical constituents in each plant. “Khi-Hood” possessed the highest antiproliferation against HCT116 with the lowest IC50 at (9.42 ± 0.46) μg/mL. The IC50 of chemotherapeutic drug (mitomycin C) was (19.12 ± 1.00) μg/mL, while both melphalan and 5-fluorouracil possessed the IC50 value higher than 50 μg/mL.ConclusionsCommonly consumed cruciferous vegetables exerted varied antiproliferation and isothiocyanate contents. High isothiocyanate content in “Khi-Hood” was contributed to high antiproliferation. Among 11 plants studied, “Khi-Hood” could be an alternative chemopreventive diet

Cytotoxic and apoptotic effects of six herbal plants against the human hepatocarcinoma (HepG2) cell line

<p>Abstract</p> <p>Background</p> <p>Six plants from Thailand were evaluated for their cytotoxicity and apoptosis induction in human hepatocarcinoma (HepG2) as compared to normal African green monkey kidney epithelial cell lines.</p> <p>Methods</p> <p>Ethanol-water crude extracts of the six plants were tested with neutral red assay for their cytotoxicity after 24 hours of exposure to the cells. Apoptotic induction was tested in the HepG2 cells with diamidino-2-phenylindole staining. DNA fragmentation, indicative of apoptosis, was analyzed with agarose gel electrophoresis. Alkylation, indicative of DNA damage, was also evaluated <it>in vitro </it>by 4-(4'-nitrobenzyl) pyridine assay.</p> <p>Results</p> <p>The extract of <it>Pinus kesiya </it>showed the highest selectivity (selectivity index = 9.6) and potent cytotoxicity in the HepG2 cell line, with an IC₅₀value of 52.0 ± 5.8 μg/ml (mean ± standard deviation). Extract of <it>Catimbium speciosum </it>exerted cytotoxicity with an IC₅₀value of 55.7 ± 8.1 μg/ml. Crude extracts from <it>Glochidion daltonii</it>, <it>Cladogynos orientalis</it>, <it>Acorus tatarinowii </it>and <it>Amomum villosum </it>exhibited cytotoxicity with IC₅₀values ranging 100-500 μg/ml. All crude extracts showed different alkylating abilities <it>in vitro</it>. Extracts of <it>P. kesiya, C. speciosum </it>and <it>C. orientalis </it>caused nuclei morphological changes and DNA laddering.</p> <p>Conclusion</p> <p>The extracts of <it>C. speciosum</it>, <it>C. orientalis </it>and <it>P. kesiya </it>induced apoptosis. Among the three plants, <it>P. kesiya </it>possessed the most robust anticancer activity, with specific selectivity against HepG2 cells.</p

Antihypertensive and antioxidant effects of dietary black sesame meal in pre-hypertensive humans

<p>Abstract</p> <p>Background</p> <p>It has been known that hypertension is an independent risk factor for cardiovascular disease (CVD). CVD is the major cause of morbidity and mortality in developed and developing countries. Elevation of blood pressure (BP) increases the adverse effect for cardiovascular outcomes. Prevention of increased BP plays a crucial role in a reduction of those outcomes, leading to a decrease in mortality. Therefore, the purpose of this study was to investigate the effects of dietary black sesame meal on BP and oxidative stress in individuals with prehypertension.</p> <p>Methods</p> <p>Twenty-two women and eight men (aged 49.8 ± 6.6 years) with prehypertension were randomly divided into two groups, 15 subjects per group. They ingested 2.52 g black sesame meal capsules or placebo capsules each day for 4 weeks. Blood samples were obtained after overnight fasting for measurement of plasma lipid, malondialdehyde (MDA) and vitamin E levels. Anthropometry, body composition and BP were measured before and after 4-week administration of black sesame meal or a placebo.</p> <p>Results</p> <p>The results showed that 4-week administration of black sesame meal significantly decreased systolic BP (129.3 ± 6.8 vs. 121.0 ± 9.0 mmHg, <it>P </it>< 0.05) and MDA level (1.8 ± 0.6 vs. 1.2 ± 0.6 μmol/L, <it>P </it>< 0.05), and increased vitamin E level (29.4 ± 6.0 vs. 38.2 ± 7.8 μmol/L, <it>P </it>< 0.01). In the black sesame meal group, the change in SBP tended to be positively related to the change in MDA (<it>R = 0.50, P </it>= 0.05), while the change in DBP was negatively related to the change in vitamin E (<it>R = -0.55, P </it>< 0.05). There were no correlations between changes in BP and oxidative stress in the control group.</p> <p>Conclusions</p> <p>These results suggest the possible antihypertensive effects of black sesame meal on improving antioxidant status and decreasing oxidant stress. These data may imply a beneficial effect of black sesame meal on prevention of CVD.</p

Drug Repurposing against KRAS Mutant G12C: A Machine Learning, Molecular Docking, and Molecular Dynamics Study

The Kirsten rat sarcoma viral G12C (KRASG12C) protein is one of the most common mutations in non-small-cell lung cancer (NSCLC). KRASG12C inhibitors are promising for NSCLC treatment, but their weaker activity in resistant tumors is their drawback. This study aims to identify new KRASG12C inhibitors from among the FDA-approved covalent drugs by taking advantage of artificial intelligence. The machine learning models were constructed using an extreme gradient boosting (XGBoost) algorithm. The models can predict KRASG12C inhibitors well, with an accuracy score of validation = 0.85 and Q2Ext = 0.76. From 67 FDA-covalent drugs, afatinib, dacomitinib, acalabrutinib, neratinib, zanubrutinib, dutasteride, and finasteride were predicted to be active inhibitors. Afatinib obtained the highest predictive log-inhibitory concentration at 50% (pIC50) value against KRASG12C protein close to the KRASG12C inhibitors. Only afatinib, neratinib, and zanubrutinib covalently bond at the active site like the KRASG12C inhibitors in the KRASG12C protein (PDB ID: 6OIM). Moreover, afatinib, neratinib, and zanubrutinib exhibited a distance deviation between the KRASG2C protein-ligand complex similar to the KRASG12C inhibitors. Therefore, afatinib, neratinib, and zanubrutinib could be used as drug candidates against the KRASG12C protein. This finding unfolds the benefit of artificial intelligence in drug repurposing against KRASG12C protein

An Insight into Sesamolin: Physicochemical Properties, Pharmacological Activities, and Future Research Prospects

Sesame seeds are rich in lignan content and have been well-known for their health benefits. Unlike the other sesame lignan compounds (i.e., sesamin and sesamol), the study of the pharmacological activity of sesamolin has not been explored widely. This review, therefore, summarizes the information related to sesamolin’s pharmacological activities, and the mechanism of action. Moreover, the influence of its physicochemical properties on pharmacological activity is also discussed. Sesamolin possessed neuroprotective activity against hypoxia-induced reactive oxygen species (ROS) and oxidative stress in neuron cells by reducing the ROS and inhibiting apoptosis. In skin cancer, sesamolin exhibited antimelanogenesis by affecting the expression of the melanogenic enzymes. The anticancer activity of sesamolin based on antiproliferation and inhibition of migration was demonstrated in human colon cancer cells. In addition, treatment with sesamolin could stimulate immune cells to enhance the cytolytic activity to kill Burkitt’s lymphoma cells. However, the toxicity and safety of sesamolin have not been reported. And there is also less information on the experimental study in vivo. The limited aqueous solubility of sesamolin becomes the main problem, which affects its pharmacological activity in the in vitro experiment and clinical efficacy. Therefore, solubility enhancement is needed for further investigation and determination of its pharmacological activity profiles. Since there are fewer reports studying this issue, it could become a future prospective research opportunity

Validation of Cell-Based Assay for Quantification of Sesamol Uptake and Its Application for Measuring Target Exposure

The intracellular drug concentration is needed for determination of target exposure at the site of action regarding its pharmacological action and adverse effects. Sesamol is an antiproliferative molecule from Sesamum indicum with promising health benefits. We present a method for measuring the intracellular sesamol content using reverse-phase HPLC with a UV diode array in melanoma cells. Sesamol was completely resolved by isocratic elution (4.152 &plusmn; 0.008 min) with methanol/water (70%, v/v) through a 30 &deg;C, 5-&micro;m C-18 column and detection at 297 nm. The present assay offers high sensitivity, fast elution, and an accurate and linear nominal concentration range of 10&ndash;1000 ng/mL (R2 = 0.9972). The % accuracy of the sesamol quality control sample was &minus;3.36% to 1.50% (bias) with a 0.84% to 5.28% relative standard deviation (RSD), representing high repeatability and high reproducibility. The % recovery was 94.80% to 99.29%, which determined that there was no loss of sesamol content during the sample preparation. The validated method was applied to monitor intracellular sesamol concentration after treatment from 5 min to 24 h. The remaining intracellular sesamol content was correlated with its antiproliferative effect (R2 = 0.9483). In conclusion, this assay demonstrated low manipulation, quick elution, and high sensitivity, precision, accuracy, and recovery, and it was successfully applied to the quantification of sesamol in target cells

Inhibition of two stages of melanin synthesis by sesamol, sesamin and sesamolin

Objective: To investigate the antimelanogenesis properties of three sesame compounds-sesamol, sesamin and sesamolin via two stages of melanin synthesis vis-à-vis sunscreen function and enzyme inhibition in melanoma cell line in order to search for alternative depigmenting agents. Methods: Antimelanogenic effects of sesame lignans were assessed in SK-MEL2 compared with the reference depigmenting agents, kojic acid and β-arbutin, in order to evaluate: (a) the sunscreen function of sesamol, sesamin and sesamolin by measurement of UV absorbtion property; (b) the inhibition of tyrosinase activity through mushroom and cellular tyrosinase; and (c) the effect on melanin content and melanogenic protein expression (tyrosinase, TRP-1 and TRP-2) by Western blot analysis; and (d) the toxicity of sesamol, sesamin and sesamolin to cells using cell cytotoxicity assay. Results: The results showed that sesamin, sesamolin and sesamol exerted satisfiable sunscreen function by absorbed UVB at 290 nm. Sesamol exhibited the highest inhibition of mushroom tyrosinase activity, but lipophilic sesamolin exhibited the highest cellular tyrosinase inhibition (IC50 of 1.6 μM) followed by sesamin, sesamol, and kojic acid, respectively. The order from high to low inhibition of melanin pigment was detected in the SK-MEL2 treated with sesamolin, sesamin, sesamol, kojic acid, and β-arbutin, respectively. Sesamolin and sesamin successfully inhibited cellular tyrosinase activity and respectively decreased TRP-1/TRP-2 (36%/15%) and TRP-1 levels (16%), thereby inhibiting melanogenesis via antityrosinase activity. No cytotoxicity to SK-MEL2 or Vero (normal) cell lines was observed at the lignan concentrations that exerted an antimelanogenic effect. Conclusions: Three sesame lignans prevent melanin synthesis through 2 stages: (a) by blocking melanin-induction and (b) by interrupting melanogenic enzyme production. This study provides evidence that sesamol, sesamin and sesamolin are potential for antimelanogenesis agents