Person: KHAN, IMRAN
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Publication Metadata only 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 Metadata only 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 Metadata only Investigating the Mechanism of Inhibition of Cyclin-Dependent Kinase 6 Inhibitory Potential by Selonsertib: Newer Insights Into Drug Repurposing(2022-05-26) Baig M. H.; Yousuf M.; Khan M. I.; KHAN I.; Ahmad I.; Alshahrani M. Y.; Hassan M. I.; Dong J.; KHAN, IMRANCopyright © 2022 Baig, Yousuf, Khan, Khan, Ahmad, Alshahrani, Hassan and Dong.Cyclin-dependent kinases (CDKs) play significant roles in numerous physiological, and are considered an attractive drug target for cancer, neurodegenerative, and inflammatory diseases. In the present study, we have aimed to investigate the binding affinity and inhibitory potential of selonsertib toward CDK6. Using the drug repurposing approach, we performed molecular docking of selonsertib with CDK6 and observed a significant binding affinity. To ascertain, we further performed essential dynamics analysis and free energy calculation, which suggested the formation of a stable selonsertib-CDK6 complex. The in-silico findings were further experimentally validated. The recombinant CDK6 was expressed, purified, and treated with selonsertib. The binding affinity of selonsertib to CDK6 was estimated by fluorescence binding studies and enzyme inhibition assay. The results indicated an appreciable binding of selonsertib against CDK6, which subsequently inhibits its activity with a commendable IC50 value (9.8 μM). We concluded that targeting CDK6 by selonsertib can be an efficient therapeutic approach to cancer and other CDK6-related diseases. These observations provide a promising opportunity to utilize selonsertib to address CDK6-related human pathologies.Publication Metadata only Herbal Medicine for Glioblastoma:Current and Future Prospects.(2020-01-29T00:00:00Z) Khan, I; Mahfooz, S; Hatiboglu, MUSTAFA AZİZ; KHAN, IMRAN; HATİBOĞLU, MUSTAFA AZİZPublication 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 Open Access 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 Open Access Therapeutic Phytochemical Actives for Potential Control of SARS-CoV-2(2021-05-01T00:00:00Z) Khan, Imran; KHAN, IMRANPublication Open Access 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 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.Publication Open Access Deciphering the role of autophagy in treatment of resistance mechanisms in glioblastoma(2021-02-01T00:00:00Z) KHAN, IMRAN; Baig, Mohammad Hassan; Mahfooz, Sadaf; Rahim, Moniba; KARAÇAM, BÜŞRA; ELBASAN, Elif Burçe; Ulasov, Ilya; Dong, Jae-June; HATİBOĞLU, MUSTAFA AZİZ; KHAN, IMRAN; KARAÇAM, BÜŞRA; ELBASAN, ELİF BURÇE; HATİBOĞLU, MUSTAFA AZİZAutophagy is a process essential for cellular energy consumption, survival, and defense mechanisms. The role of autophagy in several types of human cancers has been explicitly explained; however, the underlying molecular mechanism of autophagy in glioblastoma remains ambiguous. Autophagy is thought to be a -double-edged sword-, and its effect on tumorigenesis varies with cell type. On the other hand, autophagy may play a significant role in the resistance mechanisms against various therapies. Therefore, it is of the utmost importance to gain insight into the molecular mechanisms deriving the autophagy-mediated therapeutic resistance and designing improved treatment strategies for glioblastoma. In this review, we discuss autophagy mechanisms, specifically its pro-survival and growth-suppressing mechanisms in glioblastomas. In addition, we try to shed some light on the autophagy-mediated activation of the cellular mechanisms supporting radioresistance and chemoresistance in glioblastoma. This review also highlights autophagy’s involvement in glioma stem cell behavior, underlining its role as a potential molecular target for therapeutic interventions.