scholarly journals Design, Synthesis and Biological Evaluation of Jahanyne Analogs as Cell Cycle Arrest Inducers

Marine Drugs ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 176 ◽  
Author(s):  
Baijun Ye ◽  
Jianmiao Gong ◽  
Qiuying Li ◽  
Shiqi Bao ◽  
Xuemei Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Biological Evaluation ◽  
Hydroxyl Group ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Design Synthesis ◽  
Cycle Arrest ◽  
Synthesis And Biological Evaluation

Jahanyne, a lipopeptide with a unique terminal alkynyl and OEP (2-(1-oxo-ethyl)-pyrrolidine) moiety, exhibits anticancer activity. We synthesized jahanyne and analogs modified at the OEP moiety, employing an α-fluoromethyl ketone (FMK) strategy. Preliminary bioassays indicated that compound 1b (FMK–jahanyne) exhibited decreased activities to varying degrees against most of the cancer cells tested, whereas the introduction of a fluorine atom to the α-position of a hydroxyl group (2b) enhanced activities against all lung cancer cells. Moreover, jahanyne and 2b could induce G0/G1 cell cycle arrest in a concentration-dependent manner.

scholarly journals Degalactotigonin, a Steroidal Glycoside from Solanum nigrum, Induces Apoptosis and Cell Cycle Arrest via Inhibiting the EGFR Signaling Pathways in Pancreatic Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Hoang Le Tuan Anh ◽  
Phuong Thao Tran ◽  
Do Thi Thao ◽  
Duong Thu Trang ◽  
Nguyen Hai Dang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Solanum Nigrum ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cycle Arrest

Degalactotigonin (1) and three other steroidal compounds solasodine (2), O-acetyl solasodine (3), and soladulcoside A (4) were isolated from the methanolic extract of Solanum nigrum, and their chemical structures were elucidated by spectroscopic analyses. The isolated compounds were evaluated for cytotoxic activity against human pancreatic cancer cell lines (PANC1 and MIA-PaCa2) and lung cancer cell lines (A549, NCI-H1975, and NCI-H1299). Only degalactotigonin (1) showed potent cytotoxicity against these cancer cell lines. Compound 1 induced apoptosis in PANC1 and A549 cells. Further study on its mechanism of action in PANC1 cells demonstrated that 1 significantly inhibited EGF-induced proliferation and migration in a concentration-dependent manner. Treatment of PANC1 cells with degalactotigonin induced cell cycle arrest at G0/G1 phase. Compound 1 induced downregulation of cyclin D1 and upregulation of p21 in a time- and concentration-dependent manner and inhibited EGF-induced phosphorylation of EGFR, as well as activation of EGFR downstream signaling molecules such as Akt and ERK.

scholarly journals Pectolinarigenin Induced Cell Cycle Arrest, Autophagy, and Apoptosis in Gastric Cancer Cell via PI3K/AKT/mTOR Signaling Pathway

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1043 ◽  
Author(s):  
Ho Lee ◽  
Venu Venkatarame Gowda Saralamma ◽  
Seong Kim ◽  
Sang Ha ◽  
Suchismita Raha ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Phase Cell ◽  
Dependent Manner ◽  
Down Regulation ◽  
Cycle Arrest ◽  
Anti Cancer

Pectolinarigenin (PEC), a natural flavonoid present in Cirsium chanroenicum and in some species of Citrus fruits, has various pharmacological benefits such as anti-inflammatory and anti-cancer activities. In the present study, we investigated the anti-cancer mechanism of PEC induced cell death caused by autophagy and apoptosis in AGS and MKN28 human gastric cancer cells. The PEC treatment significantly inhibited the AGS and MKN28 cell growth in a dose-dependent manner. Further, PEC significantly elevated sub-G1 phase in AGS cells and G2/M phase cell cycle arrest in both AGS and MKN28 cells. Apoptosis was confirmed by Annexin V and Hoechst 33342 fluorescent staining. Moreover, Immunoblotting results revealed that PEC treatment down-regulated the inhibitor of apoptosis protein (IAP) family protein XIAP that leads to the activation of caspase-3 thereby cleavage of PARP (poly-ADP-ribose polymerase) in both AGS and MKN28 cells in a dose-dependent manner. The autophagy-inducing effect was indicated by the increased formation of acidic vesicular organelles (AVOs) and increased protein levels of LC3-II conversion in both AGS and MKN28 cells. PEC shows the down regulation of PI3K/AKT/mTOR pathway which is a major regulator of autophagic and apoptotic cell death in cancer cells that leads to the down-regulation of p-4EBP1, p-p70S6K, and p-eIF4E in PEC treated cells when compared with the untreated cells. In conclusion, PEC treatment might have anti-cancer effect by down-regulation of PI3K/AKT/mTOR pathway leading to G2/M phase cell cycle arrest, autophagic and apoptotic cell death in human gastric cancer cells. Further studies of PEC treatment can support to develop as a potential alternative therapeutic agent for human gastric carcinoma.

scholarly journals Antitumor and apoptotic effects of bergaptol are mediated via mitochondrial death pathway and cell cycle arrest in human breast carcinoma cells

2016 ◽  
Vol 11 (2) ◽  
pp. 489 ◽  
Author(s):  
Zhi-Cheng Ge ◽  
Xiang Qu ◽  
He-Fen Yu ◽  
Hui-Ming Zhang ◽  
Zi-Han Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cell Cycle Arrest ◽  
Research Work ◽  
Dependent Manner ◽  
Human Breast ◽  
Concentration Dependent Manner ◽  
Cycle Arrest ◽  
Apoptotic Effects ◽  
Mcf 7

<p class="Abstract">The aim of the present research work was to investigate the anti-cancer and apoptotic effects of bergaptol in human breast cancer cells (MCF-7). The effects on cell cycle arrest and caspase activation were evaluated. MTT assay was used to evaluate the effect of the compound on cell viability. Cellular morphology was demonstrated by fluorescence microscopy. Flow cytometry was used to analyze effect of bergaptol on cell cycle and apoptosis. The results revealed that bergaptol induced dose-dependent cytotoxic effect on MCF-7 cell viability showing IC<sub>50</sub> value of 52.2 µM. Bergaptol induced both early and late apoptosis in concentration-dependent manner. After treatment with bergaptol, an increase in the proportion of cells in the S-phase (37.2, 45.3 and 65.1% as compared to 28.6% in untreated cells) and a reduction in the fraction of cells in the G1 phase (44.1, 41.6 and 35.2% as compared to 51.2% in the untreated cells) was observed.</p><p> </p>

Beta-Caryophyllene Suppresses Ovarian Cancer Proliferation by Inducing Cell Cycle Arrest and Apoptosis

2020 ◽  
Vol 20 (13) ◽  
pp. 1530-1537 ◽  
Author(s):  
Santhosh Arul ◽  
Harinee Rajagopalan ◽  
Jivitesh Ravi ◽  
Haripriya Dayalan
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Parp Cleavage ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Proliferative Effect ◽  
Cycle Arrest

Background: Ovarian cancer is the fifth most common cause of cancer deaths among women with lesser prognostics. Current treatment options are chemotherapy with platinum and taxane based chemotherapy. β-Caryophyllene (BCP) an essential oil found in many plant species is known to possess an anti-proliferative effect. Objective: We aimed to investigate the antiproliferative, cytotoxic, and apoptotic role of BCP against ovarian cancer cells PA-1 and OAW 42. Methods: The antiproliferative effect of BCP was determined by MTT assay and cell viability by trypan blue exclusion assay. Cell cycle and live/dead cell analyses were performed by flow cytometry to determine cell cycle distribution and apoptosis, respectively. Results: Results of MTT assay proved the anti-proliferative effect of BCP in a dose and time-dependent manner in ovarian cancer cells. Cell cycle analysis showed that BCP induced S Phase arrest in OAW 42 cells. Results of apoptosis assay confirmed the apoptosis inducing potential of BCP in ovarian cancer cells. The apoptosis is mediated by caspase-3 activation and PARP cleavage. Conclusion: The results of our present study prove that BCP exerts its action partly by inducing cell cycle arrest and apoptosis in ovarian cancer. We conclude that BCP is a potential anti-cancer agent.

scholarly journals New Diterpenoids from Mesona procumbens with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells

2021 ◽  
Vol 14 (11) ◽  
pp. 1108
Author(s):  
Hung-Tse Huang ◽  
Chia-Ching Liaw ◽  
Yu-Chi Lin ◽  
Geng-You Liao ◽  
Chih-Hua Chao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Ros Generation ◽  
Human Leukemia ◽  
Dependent Manner ◽  
U937 Cells ◽  
Cycle Arrest ◽  
Antiproliferative Activities

Mesona procumbens is a popular material used in foods and herbal medicines in Asia for clearing heat and resolving toxins. However, phytochemical research on this plant is very rare. In this study, eleven new diterpenoids, mesonols A-K (1–11), comprising seven ent-kauranes, three ent-atisanes, and one sarcopetalane, were isolated from its methanolic extract. Structural elucidation of compounds 1–11 was performed by spectroscopic methods, especially 2D NMR, HRESIMS, and X-ray crystallographic analysis. All isolates were assessed for their antiproliferative activity, and compounds 1-4 showed potential antiproliferative activities against A549, Hep-3B, PC-3, HT29, and U937 cancer cells, with IC50 values ranging from 1.97 to 19.86 µM. The most active compounds, 1 and 2, were selected for further investigation of their effects on cell cycle progression, apoptosis, and ROS generation in U937 human leukemia cancer cells. Interestingly, it was found that compounds 1 and 2 induced antiproliferative effects in U937 cells through different mechanisms. Compound 1 caused cell cycle arrest at the G2/M phase and subsequent cell death in a dose- and time-dependent manner. However, 2-mediated antiproliferation of U937 cells triggered ROS-mediated mitochondrial-dependent apoptosis. These results provide insight into the molecular mechanism involved in the antiproliferative activities of compounds 1 and 2 in U937 cells. Altogether, the study showed that new diterpenoid compounds 1 and 2 from M. procumbens are potent and promising anticancer agents.

scholarly journals Endophytic Streptomyces sp. LRE541 isolated from Lilium davidii var. Unicolor Cotton as a Cell Factory for Antimicrobials and Anticarcinogens with Inducing Apoptosis and Cell Cycle Arrest Properties

2020 ◽  
Author(s):  
Aiai Ma ◽  
Xinge Qi ◽  
Kan Jiang ◽  
Bin Chen ◽  
Junlin Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Bioactive Metabolites ◽  
Cell Factory ◽  
Dependent Manner ◽  
Etoac Extract ◽  
Cycle Arrest ◽  
Dose Dependent ◽  
Lilium Davidii

Abstract Background: Endophytic actinomycetes, as emerging sources of bioactive metabolites, play a vital role in pharmaceutical development. Recent reports demonstrated that endophytic Streptomyces isolates could yield compounds with potent anticancer and antimicrobial properties that may be developed into chemotherapeutic drugs. Our study displayed that Streptomyces sp. LRE541 obtained from the root tissues of Lilium davidii var. unicolor Cotton, could be a potential source of anticarcinogens and antimicrobials.Results: Isolate LRE541 was characterized and identified as belonging to the genus Streptomyces based on the 16S rDNA sequence analysis, with highest sequence similarity to Streptomyces tauricus JCM4837T (98.81%). It produced extensively branched red substrate and vivid pink aerial hyphae that changed into amaranth, with elliptic spores sessile to the aerial mycelia. The secondary metabolites (EtOAc extract) produced by isolate LRE541 exhibited significant anticancer activities with IC50 values of 0.021, 0.2904, 1.484, 4.861, 6.986, 8.106, 10.87, 12.98, and 16.94 μg/mL against cancer cells RKO, 7901, HepG2, CAL-27, MCF-7, K562, Hela, SW1190 and A549, respectively, evaluated by the MTT assay. In contrast, the EtOAc extract showed less cytotoxicity activity against the normal human pulmonary artery endothelial cell (HPAEC) with an IC50 value of > 20 μg/mL than that of the cancer cells. To further explore the mechanism underlying the decrease in viability of cancer cells following the EtOAc extract treatment, cell apoptosis and cell cycle arrest assays were performed using two cancer cell lines, RKO and 7901. The result demonstrated that the EtOAc extract inhibited cell proliferation of RKO and 7901 cells by causing cell cycle arrest both at the S phase and inducing apoptosis in a dose‑dependent manner. Moreover, the EtOAc extract of isolate LRE541 with the concentrations within 100 μg/mL also possessed the antagonistic activities against E. coli ATCC 25922, MRSA ATCC 25923, P. aeruginosa and C. albicans ATCC 66415, and the antagonistic potent against the tested pathogens all displayed a dose-dependent manner. The UHPLC-MS/MS analysis of the EtOAc extract revealed that the presence of antitumor, potential antitumor and antimicrobial compounds could account for the potent antineoplasmic and antagonistic properties of the extract. Conclusion: This study provides the potential therapeutic applications of the bioactive metabolites from Streptomyces sp. LRE541 as novel antimicrobial and anticancer agents.

scholarly journals Corosolic acid induces potent anti-cancer effects in CaSki cervical cancer cells through the induction of apoptosis, cell cycle arrest and PI3K/Akt signalling pathway

2016 ◽  
Vol 11 (2) ◽  
pp. 453 ◽  
Author(s):  
Yong Qian Xu ◽  
Jian Hai Zhang ◽  
Xing Sheng Yang
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Video Clip ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Corosolic Acid ◽  
Cervical Cancer Cells ◽  
Dose Dependent

<p class="Abstract">The main objective of the present study was to investigate the anti-tumor activity of corosolic acid in CaSki human cervical cancer cells. Fluorescence and phase contrast microscopic techniques were used to study the effect of the compound on cellular morphology and apoptosis. Results revealed that corosolic acid exerted potent, dose- and time-dependent growth inhibitory effects in CaSki cell proliferation. Cells got detached from one another making clusters of small number of cells floating in the medium. After the cells were treated with 10, 50 and 100 µM concentrations of corosolic acid, cells began to emit orange red fluorescence more heavily at the centre of cells indicating apoptosis. Corosolic acid also induced G2/M cell cycle arrest in a dose-dependent manner. Increasing doses of corosolic acid treatment to these cells resulted in significant and dose-dependent down-regulation of PI3K and Akt protein expressions.</p><p><strong>Video Clip</strong></p><p><a href="https://youtube.com/v/N4EivZECRZE">Western blot assay</a>: 2 min 1 sec  </p>

scholarly journals The Novel Herbal Cocktail AGA Alleviates Oral Cancer through Inducing Apoptosis, Inhibited Migration and Promotion of Cell Cycle Arrest at SubG1 Phase

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3214
Author(s):  
Jui-Hua Lu ◽  
Yen-Ru Chou ◽  
Yue-Hua Deng ◽  
Mao-Suan Huang ◽  
Shaw-Ting Chien ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Oral Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Dependent Manner ◽  
Cell Cycle Regulators ◽  
Inhibitory Protein ◽  
Migration Ability ◽  
Cycle Arrest

Traditional Chinese medicines Antler’s extract (A) and Ganoderma lucidum (G) and Antrodia Camphorata (A) have been known to individually contain a plethora of bioactive factors including triterpenoids, polysaccharides etc., exerting various curative impacts such as anti-inflammatory, anti-oxidative, anti-atherosclerotic and anti-viral activities. However, their combinatorial therapeutic efficacy for oral cancer has not been investigated. Hence, we synthesized a robust cocktail called AGA and investigated its anti-oral cancer potential in vitro and in vivo. An MTT assay revealed the IC50 of AGA to be about 15 mg at 72 h. Therefore, 10 mg and 20 mg doses were selected to study the effect of AGA. The AGA significantly inhibited proliferation of oral cancer cells (HSC3, SAS, and OECM-1) in a dose- and time-dependent manner. AGA retarded cell cycle regulators (CDK4, CDK6, cyclin A, B1, D1 and E2) and apoptosis inhibitory protein Bcl-2, but enhanced pro-apoptotic protein Bax and a higher percentage of cells in Sub-G1 phase. Mechanistically, AGA suppressed all EMT markers; consequently, it decreased the migration ability of cancer cells. AGA significantly reduced xenograft tumor growth in nude mice with no adverse events in liver and renal toxicity. Conclusively, AGA strongly inhibited oral cancer through inducing apoptosis and inhibiting the migration and promotion of cell cycle arrest at subG1 phase, which may be mediated primarily via cocktail-contained triterpenoids and polysaccharides.

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