Andrographolide Inhibits Proliferation of Colon Cancer SW-480 Cells via Downregulating Notch Signaling Pathway.

Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Mohd Saeed ◽  
Irfan Ahmad ◽  
Irfan A. Ansari

Background: 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.

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 761
Author(s):  
Fahad Khan ◽  
Pratibha Pandey ◽  
Niraj Kumar Jha ◽  
Mohammad Khalid ◽  
Shreesh Ojha

Natural dietary molecules such as flavonoids have been recognized for their immense potential in cancer therapeutics with several health benefits. Hes-1 and Notch-1 overexpression has been associated with the progression of cervical cancer. However, the apoptosis-inducing potential of one such potent flavanol against these two key components of the Notch signaling pathway in cervical cancer has not been elucidated to date. Therefore, in this study, we performed several in vitro assays to gain detailed insight about the apoptotic inducing effect of rutin as well as its modulatory effect on Notch-1 and Hes-1 in cervical cancer cells. The results indicated that rutin led to a dose-dependent antiproliferative effects on Caski cervical cancer cells. DAPI and Mitotracker red staining revealed that rutin induced significant apoptotic effects via caspase-3/9 activation, ROS generation, and alteration in Bax/Bcl2 mRNA expression. Cell cycle analysis resulted in the arrest of cell cycle progression in G0/G1 that was associated with a reduced expression of CDK4 and Cyclin D1. The gene expression analysis further revealed that rutin treatment decreases Notch-1 and Hes-1 mRNA expression. Altogether, these results showed that rutin showed potent anticancer effects in human cervical cancer Caski cells by triggering apoptosis, G0/G1 phase arrest, and downregulating the level of Notch-1 and Hes-1 of the Notch signaling pathway.


2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
Minhui Su ◽  
Fang Tian ◽  
Bingchen Ouyang ◽  
Xiaoyu Wu ◽  
Feng Guo ◽  
...  

Systemic sclerosis (SSc) is a rare chronic autoimmune disorder, mainly characterized by skin sclerosis. In this study, Bufei Qingyu Granules (BQG), a Chinese herbal formula, was used to treat SSc. To better understand the effects and molecular mechanisms of BQG, we successfully established a Bleomycin- (BLM-) induced SSc mouse model, and the mice were treated by BQG. Meanwhile, transcriptomic and bioinformatics analyses were conducted on those samples. As a result, we visually showed that BQG ameliorated the overall health of mice, including body weight, spleen, and thymus index. Thus, it also significantly alleviated inflammation presented by Chemokine (C-X-C motif) ligand 2 (Cxcl2), vasculopathy characterized by α-smooth muscle actin (α-SMA), and fibrotic changes elaborated by not only pathological images, but also the hydroxyproline (HYP) content. After testing by transcriptomic analysis, Cxcl2, Synaptosomal-associated protein 25 (Snap25), and Eukaryotic translation initiation factor 3, and subunit J2 (Eif3j2) which were differentially expressed genes, were verified, so that the data were credible. We further found that BQG could regulate Notch signaling pathway by significantly decreasing both mRNA and protein expression levels of Notch-1 and Jagged-2. Hence, this study demonstrated that BQG could ameliorate the sclerotic skin in mice model involved in inflammation, vascular changes, and fibrosis effects, which was partly mediated by Notch signaling pathway.


2004 ◽  
Vol 1 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Mika Matsui ◽  
Sachie Fujita ◽  
Shunichi Suzuki ◽  
Hiroshi Matsuno ◽  
Satoru Miyano

Summary Matsuno et al.[1] modeled and simulated that multicellular patterning by the Drosophila Delta-Notch signaling pathway by using the software “Genomic Object Net” which was developed based on hybrid functional Petri net (HFPN) architecture. In this model, cellular formation is fixed throughout the simulation. This paper constructs an HFPN model of the Xenopus cell cycle pathway, which includes the mechanism for cell division control as well as checkpoint processes. This model simulates dynamic cell division processes of the early Xenopus embryo, including the changes in cell division cycles from synchronous to asynchronous.


2018 ◽  
Vol 154 (6) ◽  
pp. S-151
Author(s):  
Dharmalingam Subramaniam ◽  
Sivapriya Ponnurangam ◽  
Prasad Dandawate ◽  
Ossama Tawfik ◽  
Roy A. Jensen ◽  
...  

Author(s):  
Luthfia Indriyani ◽  
Adam Hermawan ◽  
Riris Istighfari Jenie

Co-chemotherapeutics approaches are increasing in cancer treatment in order mainly to suppress the resistence phenomenon of cancer treatment and to enhance the cytotoxic effect of the main chemotherapeutics agent. Tangeretin has been known to have cytotoxic effect to some cancer cells through some pathways in the cells. To explore the potential effect of tangeretin as co-chemotherapeutics agent this research was subjected to study the cytotoxic effect of tangeretin in combination with 5-Fluoro Uracil (5-FU) on WiDr colon cancer cells covering the modulation of cell cycle and apoptosis induction. Cytotoxic effect was examined by using MTT assay while apoptotis induction was determined by annexin-V flowcytometry. Under MTT assay, tangeretin showed weak cytotoxic activity on the cells. However, tangeretin significantly enhanced the cytotoxic effect of 5-FU on the cells. This co-chemotherapeutics effect likely correlated with cell cycle modulation effect, especially in inducing polyploidy phenomenon as expressed in the flowcytometric graph of the DNA content. This combination also increased apoptosis induction. These result suggest that tangeretin is potential to be developed as co-chemotherapeutic agent for 5-Fu on colon cancer and further molecular mechanism need to be explored.Keywords: Tangeretin, 5-Fluorourasil, WiDr, cell cycle, apoptosis.


2012 ◽  
Author(s):  
Dharmalingam Subramaniam ◽  
Sivapriya Ponnurangam ◽  
Satish Ramalingam ◽  
Zhiyun He ◽  
Youcheng Zhang ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Prasad Dandawate ◽  
Dharmalingam Subramaniam ◽  
Peyton Panovich ◽  
David Standing ◽  
Balaji Krishnamachary ◽  
...  

2019 ◽  
Vol 464 (1-2) ◽  
pp. 181-191
Author(s):  
Hara Afaloniati ◽  
George S. Karagiannis ◽  
Emmanouel Karavanis ◽  
Theophano A. Psarra ◽  
Anastasios Karampatzakis-Kouritas ◽  
...  

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