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Ovarian cancer is the leading cause of cancer related deaths in women. Genetic alterations including overexpression of EGFR play a crucial role in ovarian carcinogenesis. Here we evaluated the effect of phenethyl isothiocyanate (PEITC) in ovarian tumor cells in vitro and in vivo. Oral administration of 12 μmol PEITC resulted in drastically suppressing ovarian tumor growth in a preclinical mouse model. Our in vitro studies demonstrated that PEITC suppress the growth of SKOV-3, OVCAR-3 and TOV-21G human ovarian cancer cells by inducing apoptosis in a concentration-dependent manner. Growth inhibitory effects of PEITC were mediated by inhibition of EGFR and AKT, which are known to be overexpressed in ovarian tumors. PEITC treatment caused significant down regulation of constitutive protein levels as well as phosphorylation of EGFR at Tyr1068 in various ovarian cancer cells. In addition, PEITC treatment drastically reduced the phosphorylation of AKT which is downstream to EGFR and disrupted mTOR signaling. PEITC treatment also inhibited the kinase activity of AKT as observed by the down regulation of p-GSK in OVCAR-3 and TOV-21G cells. AKT overexpression or TGF treatment blocked PEITC induced apoptosis in ovarian cancer cells. These results suggest that PEITC targets EGFR/AKT pathway in our model. In conclusion, our study suggests that PEITC could be used alone or in combination with other therapeutic agents to treat ovarian cancer. 相似文献
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Prabodh K. Trivedi Pravendra Nath Prafullachandra V. Sane 《Journal of biosciences》1997,22(3):345-355
The photoinhibition of photosynthesis was investigated on intact attached leaves and isolated thylakoid membranes of
Populus deltoides.Our studies demonstrate that in intact leaves photoinhibition takes place under high irradiance which is more pronounced at
higher temperatures. No net loss of Dl and other proteins associated with photosystem II (PSII) were observed even after 64
% photoinhibition suggesting that the degradation of polypeptides associated with PSII is not the only key step responsible
for photoinhibition as observed by other workers. Electron transport studies in isolated thylakoid membranes suggested water
oxidation complex as one of the damaged site during high light exposure. The possible mechanisms of photoinhibition without
net loss of D1 protein are discussed. 相似文献
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The Essential Oil Compositions of Ocimum basilicum from Three Different Regions: Nepal,Tajikistan, and Yemen 下载免费PDF全文
Farukh S. Sharopov Prabodh Satyal Nasser A. Awadh Ali Suraj Pokharel Hanjing Zhang Michael Wink Muhammadsho A. Kukaniev William N. Setzer 《化学与生物多样性》2016,13(2):241-248
The aerial parts of Ocimum basilicum L. were collected from four different geographical locations, Sindhuli and Biratnagar (Nepal), Chormaghzak village (Tajikistan), and Sana'a (Yemen). The essential oils were obtained by hydrodistillation and analyzed by gas chromatography/mass spectrometry. A cluster analysis of 179 essential oil compositions revealed six major chemotypes: Linalool, eugenol, estragole, methyl eugenol, 1,8‐cineole, and geraniol. All four of the basil oils in this study were of the linalool‐rich variety. Some of the basil oils were screened for bioactivity including antimicrobial, cytotoxicity in human cancer cells, brine shrimp lethality, nematicidal, larvicidal, insecticidal, and antioxidant. The basil oils in this study were not notably antibacterial, cytotoxic, antioxidant, nor nematicidal, but were active in the brine shrimp lethality test, and did show larvicidal and insecticidal activities. 相似文献
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Shafat Ali Rupali Chopra Siddharth Manvati Yoginder Pal Singh Nabodita Kaul Anita Behura Ankit Mahajan Prabodh Sehajpal Subash Gupta Manoj K. Dhar Gagan B. N. Chainy Amarjit S. Bhanwer Swarkar Sharma Rameshwar N. K. Bamezai 《PloS one》2013,8(3)
Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p<5.5E−04) with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value = 2.05E−08) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR)<1.38 increased to OR = 2.44, (95%CI = 1.67–3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D. 相似文献
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Jurnal Reang Kalicharan Sharma Prabodh C. Sharma Vivek Yadav Vinita Sharma Jaseela Majeed 《Journal of biochemical and molecular toxicology》2023,37(5):e23321
Vascular endothelial growth factor receptor-2 (VEGFR-2) is crucial in promoting tumor angiogenesis and cancer metastasis. Thus, inhibition of VEGFR-2 has appeared as a good tactic for cancer treatment. To find out novel VEGFR-2 inhibitors, first, the PDB structure of VEGFR-2, 6GQO, was selected based on atomic nonlocal environment assessment (ANOLEA) and PROCHECK assessment. 6GQO was then further used for structure-based virtual screening (SBVS) of different molecular databases, including US-FDA approved drugs, US-FDA withdrawn drugs, may bridge, MDPI, and Specs databases using Glide. Based on SBVS, receptor fit, drug-like filters, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of 427877 compounds, the best 22 hits were selected. From the 22 hits, hit 5 complex with 6GQO was put through molecular mechanics/generalized born surface area (MM/GBSA) study and hERG binding. The MM/GBSA study revealed that hit 5 possesses lesser binding free energy with more inferior stability in the receptor pocket than the reference compound. The VEGFR-2 inhibition assay of hit 5 disclosed an IC50 of 165.23 nM against VEGFR-2, which can be possibly enhanced through structural modifications. 相似文献
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Vibha Pandey Abhishek Niranjan Neelam Atri K. Chandrashekhar Manoj K. Mishra Prabodh K. Trivedi Pratibha Misra 《Planta》2014,239(6):1217-1231
Glycosylation of sterols, catalysed by sterol glycosyltransferases (SGTs), improves the sterol solubility, chemical stability and compartmentalization, and helps plants to adapt to environmental changes. The SGTs in medicinal plants are of particular interest for their role in the biosynthesis of pharmacologically active substances. WsSGTL1, a SGT isolated from Withania somnifera, was expressed and functionally characterized in transgenic tobacco plants. Transgenic WsSGTL1-Nt lines showed an adaptive mechanism through demonstrating late germination, stunted growth, yellowish-green leaves and enhanced antioxidant system. The reduced chlorophyll content and chlorophyll fluorescence with decreased photosynthetic parameters were observed in WsSGTL1-Nt plants. These changes could be due to the enhanced glycosylation by WsSGTL1, as no modulation in chlorophyll biogenesis-related genes was observed in transgenic lines as compared to wildtype (WT) plants. Enhanced accumulation of main sterols like, campesterol, stigmasterol and sitosterol in glycosylated form was observed in WsSGTL1-Nt plants. Apart from these, other secondary metabolites related to plant’s antioxidant system along with activities of antioxidant enzymes (SOD, CAT; two to fourfold) were enhanced in WsSGTL1-Nt as compared to WT. WsSGTL1-Nt plants showed significant resistance towards Spodoptera litura (biotic stress) with up to 27 % reduced larval weight as well as salt stress (abiotic stress) with improved survival capacity of leaf discs. The present study demonstrates that higher glycosylation of sterols and enhanced antioxidant system caused by expression of WsSGTL1 gene confers specific functions in plants to adapt under different environmental challenges. 相似文献
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