Synthesis and Antiproliferative Activity of 2,4,6,7-Tetrasubstituted-2H-pyrazolo[4,3-c]pyridines

A library of 2,4,6,7-tetrasubstituted-2H-pyrazolo[4,3-c]pyridines was prepared from easily accessible 1-phenyl-3-(2-phenylethynyl)-1H-pyrazole-4-carbaldehyde via an iodine-mediated electrophilic cyclization of intermediate 4-(azidomethyl)-1-phenyl-3-(phenylethynyl)-1H-pyrazoles to 7-iodo-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridines followed by Suzuki cross-couplings with various boronic acids and alkylation reactions. The compounds were evaluated for their antiproliferative activity against K562, MV4-11, and MCF-7 cancer cell lines. The most potent compounds displayed low micromolar GI50 values. 4-(2,6-Diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol proved to be the most active, induced poly(ADP-ribose) polymerase 1 (PARP-1) cleavage, activated the initiator enzyme of apoptotic cascade caspase 9, induced a fragmentation of microtubule-associated protein 1-light chain 3 (LC3), and reduced the expression levels of proliferating cell nuclear antigen (PCNA). The obtained results suggest a complex action of 4-(2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol that combines antiproliferative effects with the induction of cell death. Moreover, investigations of the fluorescence properties of the final compounds revealed 7-(4-methoxyphenyl)-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine as the most potent pH indicator that enables both fluorescence intensity-based and ratiometric pH sensing.

Download Full-text

Djulis (Chenopodium Formosanum) Prevents Colon Carcinogenesis via Regulating Antioxidative and Apoptotic Pathways in Rats

Nutrients ◽

10.3390/nu11092168 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2168 ◽

Cited By ~ 7

Author(s):

Chih-Wei Lee ◽

Hong-Jhang Chen ◽

Gui-Ru Xie ◽

Chun-Kuang Shih

Keyword(s):

Colon Cancer ◽

Colon Carcinogenesis ◽

Aberrant Crypt Foci ◽

Nuclear Antigen ◽

Preneoplastic Lesions ◽

Caspase 9 ◽

Cereal Product ◽

Chemopreventive Effect ◽

Apoptotic Pathways ◽

Proliferating Cell

Djulis is a cereal crop rich in polyphenols and dietary fiber that may have nutraceutical activity to prevent colon cancer. This study was designed to examine the preventive effect of djulis on colon carcinogenesis in rats treated with 1,2-dimethylhydrazine (DMH). Rats were fed different AIN-93G-based diets: groups N and DMH were fed AIN-93G diet and groups LD, MD, and HD were fed AIN-93G diet containing 5, 10, and 20% djulis, respectively. All rats except for group N were injected with DMH to induce colon carcinogenesis. After 10 weeks, rats were sacrificed and colon and liver tissues were collected for analysis. The results showed that djulis-treated rats had significantly lower numbers of colonic preneoplastic lesions, aberrant crypt foci (ACF), sialomucin-producing (SIM)-ACF, and mucin-depleted foci. Djulis treatment increased superoxide dismutase and catalase activities in colon and liver. Djulis also reduced p53, Bcl-2, and proliferating cell nuclear antigen expressions and increased Bax and caspase-9 expressions. Besides, phenolic compounds and flavonoids were found rich in djulis. These results demonstrate the chemopreventive effect of djulis on carcinogen-induced colon carcinogenesis via regulating antioxidative and apoptotic pathways in rats. Djulis may have the potential to be developed as a valuable cereal product for chemoprevention of colon cancer.

Download Full-text

Faculty Opinions recommendation of Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717961634.793464454 ◽

2012 ◽

Author(s):

Domenico Maiorano

Keyword(s):

Proliferating Cell Nuclear Antigen ◽

Binding Protein ◽

Translesion Synthesis ◽

Nuclear Antigen ◽

Proliferating Cell

Download Full-text

Effect of Xiaotan Sanjie Recipe on growth of transplanted tumor and expressions of proliferating cell nuclear antigen and epidermal growth factor receptor in tissue of gastric carcinoma of nude mice

Journal of Chinese Integrative Medicine ◽

10.3736/jcim20070414 ◽

2007 ◽

pp. 432-436 ◽

Cited By ~ 3

Author(s):

Xiaodong Guo

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Gastric Carcinoma ◽

Proliferating Cell Nuclear Antigen ◽

Growth Factor Receptor ◽

Nuclear Antigen ◽

Transplanted Tumor ◽

Epidermal Growth ◽

Proliferating Cell

Download Full-text

The Anti-Proliferative Activity of Anisosciadone: A New Guaiane Sesquiterpene from Anisosciadium lanatum

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190308112732 ◽

2019 ◽

Vol 19 (9) ◽

pp. 1114-1119 ◽

Cited By ~ 2

Author(s):

Ahmed A. Mahmoud ◽

Wael M. El-Sayed

Keyword(s):

Anticancer Agents ◽

Antiproliferative Activity ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Chemical Constituents ◽

Spectroscopic Techniques ◽

Significant Activity ◽

Caspase 9 ◽

P53 Expression ◽

Expression And Activity

Background: The increase in cancer rate and the development of resistant tumors require a continuous search for new anticancer agents. Aims: This study aimed to analyze and identify the chemical constituents of Anisosciadium lanatum, and to investigate the antiproliferative activity of the identified constituents against various human cell lines (HepG2, MCF7, HT29, A549, and PC3) along with the possible molecular mechanisms involved. Methods: The structure of the isolated compounds was determined by spectroscopic techniques including HRFABMS, GC-MS, IR, and 400 MHz 1D and 2D NMR analyses (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOESY). The antiproliferative activity and IC50 value of the isolated compounds were measured and compared to doxorubicin. Results: A new guaiane sesquiterpene containing a rare epoxide structural element, 10β,11β−epoxy−1α,4β,5β,7αΗ- guaiane-9-one, anisosciadone (1), and stigmasterol (2) have been isolated from the plant. Anisosciadone (1) showed a significant antiproliferative activity against liver, colon, and lung cells only, while stigmasterol (2) had a significant activity against liver, colon, and breast cells. Both 1 and 2 caused no cytotoxicity to normal fibroblasts. Anisosciadone elevated the expression and activity of Caspase 3 as well as p53 expression without affecting Caspase 9 in HepG2 cells. It also caused ~ 50% downregulation in cdk1 expression. Conclusion: Taken together, anisosciadone was specific in action against cancer cells and induced apoptosis in liver cells. It also has a unique feature by elevating the expression and activity of Caspase 3 without affecting the initiator Caspase 9. Therefore, anisosciadone deserves more investigation as a targeted therapy for cancer.

Download Full-text

The Prognostic Value of Cell Proliferation in Colorectal Adenomas Assessed with Tritiated Thymidine and Anti-Proliferating Cell Nuclear Antigen

Cancer Detection and Prevention ◽

10.1046/j.1525-1500.1999.09904.x ◽

1999 ◽

Vol 23 (1) ◽

pp. 57-63 ◽

Cited By ~ 2

Author(s):

Giulia Ottaviani ◽

Anna Maria Lavezzi ◽

Fausto De Ruberto ◽

Giuseppe Fichera ◽

Luigi Matturri

Keyword(s):

Cell Proliferation ◽

Proliferating Cell Nuclear Antigen ◽

Prognostic Value ◽

Tritiated Thymidine ◽

Colorectal Adenomas ◽

Nuclear Antigen ◽

Proliferating Cell

Download Full-text

Brassinin Inhibits Proliferation in Human Liver Cancer Cells via Mitochondrial Dysfunction

Cells ◽

10.3390/cells10020332 ◽

2021 ◽

Vol 10 (2) ◽

pp. 332

Author(s):

Taeyeon Hong ◽

Jiyeon Ham ◽

Jisoo Song ◽

Gwonhwa Song ◽

Whasun Lim

Keyword(s):

Mitochondrial Dysfunction ◽

Cancer Cells ◽

Cell Lines ◽

Mapk Pathway ◽

Mapk Signaling ◽

Nuclear Antigen ◽

Cruciferous Vegetable ◽

Antiproliferative Effects ◽

Hep3b Cells ◽

Human Liver Cancer Cells

Brassinin is a phytochemical derived from Chinese cabbage, a cruciferous vegetable. Brassinin has shown anticancer effects on prostate and colon cancer cells, among others. However, its mechanisms and effects on hepatocellular carcinoma (HCC) have not been elucidated yet. Our results confirmed that brassinin exerted antiproliferative effects by reducing proliferating cell nuclear antigen (PCNA) activity, a proliferation indicator and inducing cell cycle arrest in human HCC (Huh7 and Hep3B) cells. Brassinin also increased mitochondrial Ca2+ levels and depolarized the mitochondrial membrane in both Huh7 and Hep3B cells. Moreover, brassinin generated high amounts of reactive oxygen species (ROS) in both cell lines. The ROS scavenger N-acetyl-L-cysteine (NAC) inhibited this brassinin-induced ROS production. Brassinin also regulated the AKT and mitogen-activated protein kinases (MAPK) signaling pathways in Huh7 and Hep3B cells. Furthermore, co-administering brassinin and pharmacological inhibitors for JNK, ERK1/2 and P38 decreased cell proliferation in both HCC cell lines more than the pharmacological inhibitors alone. Collectively, our results demonstrated that brassinin exerts antiproliferative effects via mitochondrial dysfunction and MAPK pathway regulation on HCC cells.

Download Full-text