Person: KHAN, IMRAN
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Publication Metadata only Glycyrrhizin induces reactive oxygen species-dependent apoptosis and cell cycle arrest at G(0)/G(1) in HPV18(+) human cervical cancer HeLa cell line(2018-01-01T00:00:00Z) Farooqui, Arshi; Khan, Fahad; Khan, IMRAN; Ansari, Irfan A.; KHAN, IMRANCervical cancer is the fourth most common cancer among women worldwide and is a major cause of morbidity and mortality. High-risk Human Papilloma Virus (mostly type 16 & 18) infection is the primary risk factor for the development of cervical carcinoma. The quest for strong, safe and cost effective natural antiproliferative agents that could reduce cervical cancer have been focussed now a day. Recently, glycyrrhizin, a triterpene glycoside (saponin) from licorice (Glycyrrhiza glabra Linn.), has been shown to exhibit potent antiproliferative and anticancer properties in a few preliminary studies. However, potential of this compound in cervical cancer has not been elucidated yet. Therefore the objective of this study was to analyze the antiproliferative and apoptotic properties of glycyrrhizin in human cervical cancer HeLa cells. Our results showed that glycyrrhizin exposure significantly reduced the cell viability of HeLa cells with a concomitant increase in nuclear condensation and DNA fragmentation in a dose dependent manner. The intracellular ROS generation assay showed dose-related increment in ROS production induced by glycyrrhizin. Glycyrrhizin also induced apoptosis in cervical cancer cells by exerting mitochondrial depolarization. Cell cycle study showed that glycyrrhizin induced cell cycle arrest in G(0)/G1 phase of cell cycle in a dose dependent manner. Thus, this study confirms the efficacy of glycyrrhizin in cervical cancer cells which could be an adjunct in the better prevention and management of cervical cancer worldwide.Publication Metadata only Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia(2017-07-01T00:00:00Z) Alvi, Sahir Sultan; Ansari, Irfan A.; Khan, IMRAN; Iqbal, Johar; Khan, M. Salman; KHAN, IMRANProprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease of the proprotien convertase (PC) family that has profound effects on plasma low density lipoprotein cholesterol (LDL-C) levels, the major risk factor for coronary heart disease (CHD), through its ability to mediate LDL receptor (LDL-R) protein degradation and reduced recycling to the surface of hepatocytes. Thus, the current study was premeditated not only to evaluate the role of lycopene in targeting the inhibition of PCSK-9 via modulation of genes involved in cholesterol homeostasis in HFD rats but also to examine a correlation between HFD induced inflammatory cascades and subsequent regulation of PCSK-9 expression. Besides the effect of lycopene on hepatic PCSK-9 gene expression, PPI studies for PCSK-9-Lycopene complex and EGF-A of LDL-R were also performed via molecular informatics approach to assess the dual mode of action of lycopene in LDL-R recycling and increased removal of circulatory LDL-C. We for the first time deciphered that lycopene treatment significantly down-regulates the expression of hepatic PCSK-9 and HMGR, whereas, hepatic LDL-R expression was significantly up-regulated. Furthermore, lycopene ameliorated inflammation stimulated expression of PCSK-9 via suppressing the expression of inflammatory markers. The results from our molecular informatics studies confirmed that lycopene, while occupying the active site of PCSK-9 crystal structure, reduces the affinity of PCSK-9 to complex with EGF-A of LDL-R, whereas, atorvastatin makes PCSK-9-EGF-A complex formation more feasible than both of PCSK-9-EGF-A alone and Lycopene-PCSK-9-EGF-A complex. Based on above results, it can be concluded that lycopene exhibits potent hypolipidemic activities via molecular mechanisms that are either identical (HMGR inhibition) or distinct from that of statins (down-regulation of PCSK-9 mRNA synthesis). To the best of our knowledge, this is the first report that lycopene has this specific biological property. Being a natural, safer and alternative therapeutic agent, lycopene could be used as a complete regulator of cholesterol homeostasis and ASCVD.Publication Metadata only Carvacrol Induces Reactive Oxygen Species (ROS)-mediated Apoptosis Along with Cell Cycle Arrest at G(0)/G(1) in Human Prostate Cancer Cells(2017-01-01T00:00:00Z) Khan, Fahad; Khan, IMRAN; Farooqui, Arshi; Ansari, Irfan A.; KHAN, IMRANCarvacrol, a major monoterpenoid phenol from Origanum and Thymus species, has been shown to exhibit antiproliferative and anticancer properties in a few recent studies. Nevertheless, detailed mechanism of the action of this compound in prostate cancer has not been elucidated yet. Therefore, in the current study, we examined the anticancer activity and mechanism of the action of carvacrol against human prostate cancer cells. It was found that the treatment of DU145 cells with carvacrol decreased cell viability in a concentration and time-dependent manner. The antiproliferative action of carvacrol leads to induction of apoptosis as confirmed by nuclear condensation, Annexin V-FITC/PI positive cells, and caspase-3 activation. In addition, carvacrol augmented reactive oxygen species generation and disruption in the mitochondrial membrane potential which has not been reported in the previous studies of carvacrol with prostate cancer. Moreover, carvacrol-induced apoptosis of prostate cancer cells was also accompanied by significant amount of growth arrest at the G(0)/G(1) phase of the cell cycle which has also not been documented previously. To sum up, this study has established that carvacrol could be a promising chemotherapeutic agent and could have a direct practical implication and translational relevance to prostate cancer patients as Origanum consumption may retard prostate cancer progression.Publication Metadata only Prediction of functionally significant single nucleotide polymorphisms in PTEN tumor suppressor gene: An in silico approach(2017-09-01T00:00:00Z) Khan, IMRAN; Ansari, Irfan A.; Singh, Pratichi; Dass, Febin Prabhu J.; KHAN, IMRANThe phosphatase and tensin homolog (PTEN) gene plays a crucial role in signal transduction by negatively regulating the PI3K signaling pathway. It is the most frequent mutated gene in many human-related cancers. Considering its critical role, a functional analysis of missense mutations of PTEN gene was undertaken in this study. Thirty five nonsynonymous single nucleotide polymorphisms (nsSNPs) within the coding region of the PTEN gene were selected for our in silico investigation, and five nsSNPs (G129E, C124R, D252G, H61D, and R130G) were found to be deleterious based on combinatorial predictions of different computational tools. Moreover, molecular dynamics (MD) simulation was performed to investigate the conformational variation between native and all the five mutant PTEN proteins having predicted deleterious nsSNPs. The results of MD simulation of all mutant models illustrated variation in structural attributes such as root-mean-square deviation, root-mean-square fluctuation, radius of gyration, and total energy; which depicts the structural stability of PTEN protein. Furthermore, mutant PTEN protein structures also showed a significant variation in the solvent accessible surface area and hydrogen bond frequencies from the native PTEN structure. In conclusion, results of this study have established the deleterious effect of the all the five predicted nsSNPs on the PTEN protein structure. Thus, results of the current study can pave a new platform to sort out nsSNPs that can be undertaken for the confirmation of their phenotype and their correlation with diseased status in case of control studies. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.Publication Metadata only Antiproliferative and Apoptotic Properties Human Colon Cancer DLD1 Cell Line of Andrographolide Against(2020-01-01T00:00:00Z) KHAN, IMRAN; Mahfooz, Sadaf; Ansari, Irfan A.; KHAN, IMRANBackground: In recent years, natural products have received great attention for cancer prevention owing to their various health benefits, noticeable lack of toxicity and side effects, and the limitations of chemotherapeutic agents. Andrographolide, a labdane diterpenoid is a principal bioactive constituent of Andrograp his paniculata Nees, exhibits significant anticancer activity.Publication Metadata only Andrographolide Exhibits Anticancer Potential Against Human Colon Cancer Cells by Inducing Cell Cycle Arrest and Programmed Cell Death via Augmentation of Intracellular Reactive Oxygen Species Level(2018-01-01T00:00:00Z) Khan, IMRAN; Khan, Fahad; Farooqui, Arshi; Ansari, Irfan A.; KHAN, IMRANAndrographolide, a diterpenoid lactone and a major constituent of Andrographis paniculata Nees, exhibits remarkable anticancer activity. However, the effect of andrographolide on colon cancer has not been completely elucidated yet. Thus, we investigated the chemopreventive potential of andrographolide in colon cancer HT-29 cells. The cytotoxic potential of andrographolide on HT-29 cells was determined by MTT assay, trypan blue exclusion assay, colony formation assay, and morphological analysis; and apoptotic property by DAPI and Hoechst staining, FITC-Annexin V assay, DNA fragmentation assay and caspase-3 activity assay. To elucidate andrographolide action, intracellular reactive oxygen species (ROS) level was determined by DCFDA dye; change in mitochondrial potential by Rhodamine123 and Mito Tracker Red CMXRos dye; and cell cycle modulatory property by flow cytometric analysis. Results of the study have shown that andrographolide decreased cell viability of HT-29 cells in a dose- and time-dependent manner. Furthermore, andrographolide induced apoptosis in HT-29 cells which seemed to be linked with augmented intracellular ROS level and disruption of mitochondrial membrane potential. Interestingly, andrographolide caused significant cell cycle arrest in G2/M phase at lower doses, but, in G0/G1 phase at higher doses. In summary, our results indicated that andrographolide exhibited antiproliferative and apoptotic properties against colon cancer HT-29 cells.Publication Metadata only Identification and characterization of functional single nucleotide polymorphisms (SNPs) in Axin 1 gene: a molecular dynamics approach(2018-06-01T00:00:00Z) Khan, IMRAN; Ansari, Irfan A.; Singh, Pratichi; Dass, J. Febin Prabhu; Khan, Fahad; KHAN, IMRANWnt signaling pathway has been reported to play crucial role in intestinal crypt formation and deregulation of this pathway is responsible for colorectal cancer initiation and progression. Axin 1, a scaffold protein, play pivotal role in the regulation of Wnt/beta-catenin signaling pathway and has been found to be mutated in several cancers; primarily in colon cancer. Considering its crucial role, a structural and functional analysis of missense mutations in Axin 1 gene was performed in this study. Initially, one hundred non-synonymous single nucleotide polymorphisms in the coding regions of Axin 1 gene were selected for in silico analysis. Six variants (G820S, G856S, E830K, L811V, L847V, and R767C) were predicted to be deleterious by combinatorial prediction. Further investigation of structural attributes confirmed two highly deleterious single nucleotide polymorphisms (G820S and G856S). Molecular dynamics simulation demonstrated variation in different structural attributes between native and two highly deleterious Axin 1 mutant models. Finally, docking analysis showed variation in binding affinity of mutant Axin 1 proteins with two destruction complex members, GSK3 beta and adenomatous polyposis. The results collectively showed the deleterious effect of the above predicted single nucleotide polymorphisms on the Axin 1 protein structure and could prove to be an adjunct in the disease genotype-phenotype correlation studies.Publication Metadata only Andrographolide Induces Apoptosis and Cell Cycle Arrest through Inhibition of Aberrant Hedgehog Signaling Pathway in Colon Cancer Cells(2020-10-01T00:00:00Z) KHAN, IMRAN; Mahfooz, Sadaf; Faisal, Mohammad; Alatar, Abdulrahman A.; Ansari, Irfan A.; KHAN, IMRANBackground Hedgehog signaling pathway (Hh) is abnormally stimulated in colon cancer. Evidence suggests the therapeutic effectiveness of andrographolide against several cancers. This study attempts to delineate the effect of andrographolide on Hh signaling pathway in colon cancer HCT-116 cells.Methods:Effects of andrographolide were studied on HCT-116 cells by evaluating cytotoxicity by MTT assay, morphology assessment, trypan blue exclusion, and colony formation assay; migratory potential by scratch assay; apoptosis by DAPI, Hoechst staining, FITC-Annexin V assay, and caspases activation; mitochondrial membrane potential (Delta psi m) by Mito Tracker and Rhodamine 123. Intracellular ROS by DCFH-DA staining. Cell cycle regulation by flow cytometry. Expression of BAX, BAD, BCL2, Cyclin B1, CDK1, Smo, and Gli1 by qRT-PCR. Interaction between andrographolide and Smo protein by in-silico molecular docking.Results:Andrographolide induced antiproliferative effect on HCT-116 cells in a dose-dependent and time-dependent manner. It also induced apoptosis and anti-migratory effect in HCT-116 cells. In combination with 5FU, andrographolide exhibited synergistic effect. It Induced G2/M phase arrest through downregulating CDK1 and Cyclin B1. Andrographolide also inhibited Hh signaling by downregulating Smo and Gli1 in HCT-116 cells. It showed high affinity toward Smo protein in-silico.Conclusion:Andrographolide repressed the colon cancer cell growth via inhibiting Hh signaling pathway.