Person: KHAN, IMRAN
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Publication Understanding and Targeting the Colon Cancer Pathogenesis: A Molecular Perspective(2022-01-01) KHAN I.; KHAN, IMRANColorectal cancer (CRC) one of the leading cause of cancer-related deaths worldwide. With the presently available knowledge on CRC, it is understood that the underlying is a complex process. The complexity of CRC lies in aberrant activation of several cellular signaling pathways that lead to activation and progression of CRC. In this context, recent studies have pointed towards the role of developmental pathways like; hedgehog (HH), wingless-related integration site (WNT/??-catenin) and Notch pathways that play a crucial role in maintenance and homeostasis of colon epithelium. Moreover, the deregulation of these signaling pathways has also been associated with the pathogenesis of CRC. Therefore, in the search for better therapeutic options, these pathways have emerged as potential targets. The present review attempts to highlight the role of HH, WNT/??-catenin and Notch pathways in colon carcinogenesis.Publication Thymoquinone Enhances the Effect of Gamma Knife in B16-F10 Melanoma Through Inhibition of Phosphorylated STAT3(2019-01-01) HATİBOĞLU, MUSTAFA AZİZ; KOÇYİĞİT, ABDÜRRAHİM; GÜLER, ERAY METİN; Akdur, Kerime; Khan, Imran; Nalli, Arife; Karataş, Ersin; TÜZGEN, SAFFET; HATİBOĞLU, MUSTAFA AZİZ; KOÇYİĞİT, ABDÜRRAHİM; GÜLER, ERAY METİN; KHAN, IMRANBACKGROUND: Patients with brain metastasis from melanoma have a dismal prognosis with poor survival time. Gamma Knife (GK) is an effective treatment to control brain metastasis from melanoma. Thymoquinone (TQ) has emerged as a potential therapeutic option due to its antiproliferative effects on various cancers. The purpose of the study was to assess the effect of GK on B16-F10 melanoma cells in vitro and intracerebral melanoma in vivo, and its synergistic effect in combination with TQ.Publication Andrographolide Inhibits Proliferation of Colon Cancer SW-480 Cells via Downregulating Notch Signaling Pathway(2020-07-01T00:00:00Z) Khan, Imran; KHAN, IMRANBackground: Recently Notch signaling pathway has gained attention as a potential therapeutic target for chemotherapeutic intervention. However, the efficacy of previously known Notch inhibitors in colon cancer is still unclear. The purpose of this study was to investigate the effect of andrographolide on aberrantly activated Notch signaling in SW-480 cells in vitro. Methods: The cytostatic potential of andrographolide on SW-480 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, morphology assessment and colony formation assay. The apoptotic activity was evaluated by FITC Annexin V assay, 4',6-diamidino-2-phenylindole (DAPI), Hoechst, Rhodamine 123 and Mito Tracker CMXRos staining. Scratch assay for migratory potential assessment. 7'-Dichlorodihydrofluorescein Diacetate (DCFH-DA) staining was used to evaluate the Reactive Oxygen Species (ROS) generation. Relative mRNA expression of Bax, Bcl2, NOTCH 1 and JAGGED 1 was estimated by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Cell cycle phase distribution was evaluated Annexin V-FITC/PI staining. Results: MTT assay demonstrated dose and time dependent cytoxicity of andrographolide on SW-480 cells. It also inhibited the migratory and colony forming potential of SW-480 cells. Furthermore, andrographolide also showed disruption of mitochondrial membrane potential and induced apoptosis through nuclear condensation. Flow cytometric evaluation showed andrographolide enhanced early and late apoptotic cells and induced upregulation of proapoptotic (Bax and Bad) and downregulation of antiapoptotic Bcl2 in treated SW-480 cells. Andrographolide augmented intracellular ROS generation and induced G0/G1 phase cell cycle arrest in colon cancer SW480 cells. Furthermore, andrographolide repressed the Notch signaling by decreasing the expression of NOTCH 1 and JAGGED 1. Conclusion: Our findings suggested that andrographolide constraint the growth of SW-480 cells through the inhibition of Notch signaling pathway.Publication 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 Can COVID-19 induce glioma tumorogenesis through binding cell receptors?(2020-06-01T00:00:00Z) Khan, Imran; KHAN, IMRANThe outbreak of Novel Coronavirus 2019 (COVID-19) represents a global threat to the public healthcare. The viral spike (S) glycoprotein is the key molecule for viral entry through interaction with angiotensin converting enzyme 2 (ACE2) receptor molecules present on the cell membranes. Moreover, it has been established that COVID-19 interacts and infects brain cells in humans via ACE2. Therefore in the light of these known facts we hypothesized that viral S protein molecule may bind to the other overexpressed receptor molecules in glioma cells and may play some role in glioma tumorogenesis. Thus we leverage docking analysis (HEX and Z-DOCK) between viral S protein and epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptors (VEGFR) and hepatocyte growth factor receptors (HGFR/c-MET) to investigate the oncogenic potential of COVID-19. Our findings suggested higher affinity of Viral S protein towards EGFR and VEGFR. Although, the data presented is preliminary and need to be validated further via molecular dynamics studies, however it paves platform to instigate further investigations on this aspect considering the aftermath of COVID-19 pandemic in oncogenic perspective.Publication 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 Therapeutic Phytochemical Actives for Potential Control of SARS-CoV-2(2021-05-01T00:00:00Z) Khan, Imran; KHAN, IMRANPublication 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 Targeting Glioblastoma: The Current State of Different Therapeutic Approaches.(2021-01-13T00:00:00Z) Khan, Imran; Elbasan, Elif Burce; Mahfooz, Sadaf; Karacam, Busra; Oztanir, MUSTAFA NAMIK; Hatiboglu, Mustafa Aziz; KHAN, IMRAN; ELBASAN, ELİF BURÇE; KARAÇAM, BÜŞRA; ÖZTANIR, MUSTAFA NAMIK; HATİBOĞLU, MUSTAFA AZİZBackground: Glioma is the primary cancer of the central nervous system in adults. Among gliomas, glioblastoma is the most deadly and aggressive form, with an average life span of 1 to 2 years. Despite implementing the rigorous standard care involving maximal surgical removal followed by concomitant radiation and chemotherapy, the patient prognosis remains poor. Due to the infiltrative nature of glioblastoma, chemo- and radio-resistance behavior of these tumors and lack of potent chemotherapeutic drugs, treatment of glioblastoma is still a big challenge. Objective: The goal of the present review is to shed some light on the present state of novel strategies, including molecular therapies, immunotherapies, nanotechnology and combination therapies for patients with glioblastoma. Methods: Peer-reviewed literature was retrieved via Embase, Ovid, PubMed and Google Scholar till the year 2020. Conclusion: Insufficient effect of chemotherapies for glioblastoma is more likely because of different drug resistance mechanisms and intrinsically complex pathological characteristics. Therefore, more advancement in various therapeutic approaches such as antitumor immune response, targeting growth regulatory and drug resistance pathways, enhancing drug delivery and drug carrier systems are required in order to establish an effective treatment approach for patients with glioblastoma.Publication 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.