Combined EGFR and c-Src Antisense Oligodeoxynucleotides Encapsulated with PAMAM Denderimers Inhibit HT-29 Colon Cancer Cell Proliferation

Nourazarian, Alireza; Gholamhoseinian, Ahmad; Farajnia, Safar; Khosroushahi, Ahmad Yari; Pashaei-Asl, Roghiyeh; Omidi, Yadollah

doi:10.7314/apjcp.2012.13.9.4751

Cited by 24 publications

(14 citation statements)

References 22 publications

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“…Our findings are in accordance with a previous study by Nourazarian et al (48), who demonstrated that combined EGFR and c-Src antisense deoxyoligonucleotides inhibited the proliferation of human colon cancer (HT29) cells. It has been reported that the blockade of Src kinase by PP2 attenuates EGFR phosphorylation at both tyrosine-845 and tyrosine-1173 residues in cervical cancer cells.…”

Section: Discussionsupporting

confidence: 94%

Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src-mediated phosphorylation of EGF receptor tyrosine kinase

et al. 2014

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Abstract. Thymoquinone (TQ), a compound isolated from black seed oil (Nigella sativa), has been reported to possess anti-inflammatory and anticancer activities. However, the molecular mechanisms underlying the anticancer effects of TQ remain poorly understood. In the present study, we found that TQ significantly reduced the viability of human colon cancer HCT116 cells in a concentration-and time-dependent manner. Treatment of cells with TQ induced apoptosis, which was associated with the upregulation of Bax and inhibition of Bcl-2 and Bcl-xl expression. TQ also activated caspase-9,-7, and -3, and induced the cleavage of poly-(ADP-ribose) polymerase (PARP). Pretreatment with a pan-caspase inhibitor, z-VAD-fmk, abrogated TQ-induced apoptosis by blocking the cleavage of caspase-3 and PARP. Treatment of cells with TQ also diminished the constitutive phosphorylation, nuclear localization and the reporter gene activity of signal transducer and activator of transcription-3 (STAT3). TQ attenuated the expression of STAT3 target gene products, such as survivin, c-Myc, and cyclin-D1, -D2, and enhanced the expression of cell cycle inhibitory proteins p27 and p21. Treatment with TQ attenuated the phosphorylation of upstream kinases, such as Janus-activated kinase-2 (JAK2), Src kinase and epidermal growth factor receptor (EGFR) tyrosine kinase. Pharmacological inhibition of JAK2 and Src blunted tyrosine phosphorylation of EGFR and STAT3, while treatment with an EGFR tyrosine kinase inhibitor gefitinib inhibited phosphorylation of STAT3 without affecting that of JAK2 and Src in HCT116 cells. Collectively, our study revealed that TQ induced apoptosis in HCT116 cells by blocking STAT3 signaling via inhibition of JAK2-and Src-mediated phosphorylation of EGFR tyrosine kinase. IntroductionColorectal cancer is one of the leading causes of mortality and ranks among the three most common cancers in developed countries (1,2). More than one million new cases of colorectal cancer are diagnosed every year (3). Multiple lines of evidence suggest that bioactive compounds present in various edible and medicinal plants can prevent colon carcinogenesis (4). Thymoquinone (TQ; Fig. 1A), a dietary phytochemical, is the major bioactive constituent present in black seed oil (Nigella sativa), which is widely consumed as a condiment and has long been used in Ayurvedic medicine. TQ has been reported to exert antioxidative, anti-inflammatory and anticancer effects (5-7). Several studies have reported that TQ inhibits cell proliferation, induces apoptosis and impedes the in vivo growth of xenograft tumors of various human cancer cells including those of the stomach (8,9), colorectal (10,11), lungs (12), breast (5) and prostate (13). In a recent study, TQ was shown to inhibit 1,2-dimethylhydrazine-induced initiation and promotion of colon carcinogenesis in Wister rats (14). However, the molecular basis of the anticancer effects of TQ in colon cancer has yet to be fully elucidated.Evasion from apoptosis is one of the hallmarks of cancer (15). Tumor cells ...

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Section: Discussionsupporting

confidence: 94%

Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src-mediated phosphorylation of EGF receptor tyrosine kinase

et al. 2014

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“…15 Then, 96-well flat-bottomed culture plates (TPP, Switzerland) were used to seed the cells into them for further MTT assay or 6-well plate (TPP, Switzerland) was applied for real time PCR and flow cytometry. Then they were incubated at 37°C in a 5% CO 2 incubator.…”

Section: Methodsmentioning

confidence: 99%

Hesa-A Effects on Cell Cycle Signaling in Esophageal Carcinoma Cell Line

Ahmadian

Pashaei-Asl

Samadi

et al. 2016

Middle East J Dig Dis

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BACKGROUNDHesa-A is a natural compound with anticancer properties. The exact mechanism of its action in esophageal cancer is not clear, yet. The aim of this study was to evaluate the cell toxicity effect of Hesa-A on the esophageal carcinoma cell lines, KYSE-30, and cell cycle genes expression.METHODSIn this study, we tested cell toxicity with MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay and flow cytometry to evaluatet he cell cycle arrest. Real time polymerase chain reaction was used to assess the expression of P53, P16, P21, cyclin D1, and cyclin B1 genes.RESULTSOur results showed that Hesa-A is effective in the expression of cell cycling check point proteins. Hesa-A induced an arrest in G2 phase of esophageal cell cycle. The levels of P53 (>13 times), P21 (>21 times), P16, cyclin B1, and cyclin D1 genes were increased 48 hours after Hesa-A treatment.CONCLUSIONP21 and P16 expression were the potential mechanisms for G2 arrest of KYSE-30 esophageal cancer cell line by Hesa-A.

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“…We have established Epidermal growth factor receptor (EGFR) and c-Src antisense oligonucleotide encapsulated with PAMAM dendrimers in human colon cancer cell line and have showed its effects on signalling pathway. 63,68,91 To confirm entry of antisense to the cell, fluorescent microscope and Fluorescence-activated cell sorting (FACS) analysis have been carried out and showed that Fluorescein isothiocyanate (FITS) are conjugated effectively to dendrimers. Our studies evaluated the antisense dendrimers mediated transfer into cells and showed the effective antisense entry inside the cell; however, the antisense alone is not able to enter the cells.…”

Section: Dendrimers-based Antisense Delivery System Approaches For Trmentioning

confidence: 99%

Legionella Pneumophila and Dendrimers-Mediated Antisense Therapy

Pashaei-Asl¹,

Khodadadi²,

Pashaei-Asl³

et al. 2017

Adv Pharm Bull

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Finding novel and effective antibiotics for treatment of Legionella disease is a challenging field. Treatment with antibiotics usually cures Legionella infection; however, if the resultant disease is not timely recognized and treated properly, it leads to poor prognosis and high case fatality rate. Legionella pneumophila DrrA protein (Defects in Rab1 recruitment protein A)/also known as SidM affects host cell vesicular trafficking through modification of the activity of cellular small guanosine triphosphatase )GTPase( Rab (Ras-related in brain) function which facilitates intracellular bacterial replication within a supporter vacuole. Also, Legionella pneumophila LepA and LepB (Legionella effector protein A and B) proteins suppress host-cell Rab1 protein’s function resulting in the cell lysis and release of bacteria that subsequently infect neighbour cells. Legionella readily develops resistant to antibiotics and, therefore, new drugs with different modes of action and therapeutic strategic approaches are urgently required among antimicrobial drug therapies;gene therapy is a novel approach for Legionnaires disease treatment. On the contrary to the conventional treatment approaches that target bacterial proteins, new treatment interventions target DNA (Deoxyribonucleic acid), RNA (Ribonucleic acid) species, and different protein families or macromolecular complexes of these components. The above approaches can overcome the problems in therapy of Legionella infections caused by antibiotics resistance pathogens. Targeting Legionella genes involved in manipulating cellular vesicular trafficking using a dendrimer-mediated antisense therapy is a promising approach to inhibit bacterial replication within the target cells.

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Combined EGFR and c-Src Antisense Oligodeoxynucleotides Encapsulated with PAMAM Denderimers Inhibit HT-29 Colon Cancer Cell Proliferation

Cited by 24 publications

References 22 publications

Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src-mediated phosphorylation of EGF receptor tyrosine kinase

Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src-mediated phosphorylation of EGF receptor tyrosine kinase

Hesa-A Effects on Cell Cycle Signaling in Esophageal Carcinoma Cell Line

Legionella Pneumophila and Dendrimers-Mediated Antisense Therapy

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