scholarly journals Effect of a novel piperazine compound on cancer cells

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
So Hyun Jeon ◽  
Cha-Gyun Shin
Keyword(s):  
Cancer Cells ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Nuclear Condensation ◽  
Anticancer Chemotherapy ◽  
Marker Proteins ◽  
Mitochondrial Signaling ◽  
Anti Cancer ◽  
Apoptotic Marker ◽  
Apoptosis In Cancer Cells

AbstractMany drugs have been developed for anticancer chemotherapy. However, more anti-cancer drugs should be developed from potential chemicals to circumvent the disadvantages of existing drugs. Most anti-cancer chemicals induce apoptosis in cancer cells. This study tested the efficiency of a new chemical, the piperazine derivative 1-[2-(Allylthio) benzoyl]-4-(4-methoxyphenyl) piperazine (CB01), on glioblastoma (U87) and cervix cancer (HeLa) cells. CB01 was highly cytotoxic to these cells (IC50S  < 50 nM) and induced the traditional apoptotic symptoms of DNA fragmentation and nuclear condensation at 40 nM. Western-blot analysis of the cell lysates revealed that the intracellular apoptotic marker proteins, such as cleaved caspase-3, cytochrome c, and Bax, were highly upregulated in the CB01-treated cells. Furthermore, increased activities of caspase-3 and -9, but not caspase-8, were observed. Therefore, these results suggest that CB01 can act as an anticancer chemotherapeutic by stimulating the intrinsic mitochondrial signaling pathway to induce cytotoxicity and apoptosis in cancer cells.

scholarly journals The Novel Benzothiazole Derivative PB11 Induces Apoptosis via the PI3K/AKT Signaling Pathway in Human Cancer Cell Lines

2021 ◽  
Vol 22 (5) ◽  
pp. 2718
Author(s):  
Jinsun Kim ◽  
Sung Hee Hong ◽  
So Hyun Jeon ◽  
Min Ho Park ◽  
Cha-Gyun Shin
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Caspase 3 ◽  
Human Cancer ◽  
Akt Signaling ◽  
Nuclear Condensation ◽  
Continuous Administration ◽  
Human Cancer Cell Lines ◽  
Benzothiazole Derivative ◽  
Anti Cancer

Among several anti-cancer therapies, chemotherapy can be used regardless of the stage of the disease. However, development of anti-cancer agents from potential chemicals must be executed very cautiously because of several problems, such as safety, drug resistance, and continuous administration. Most chemotherapeutics selectively cause cancer cells to undergo apoptosis. In this study, we tested the effects of a novel chemical, the benzothiazole derivative N-[2-[(3,5-dimethyl-1,2-oxazol-4-yl)methylsulfanyl]-1,3-benzothiazol-6-yl]-4-oxocyclohexane-1-carboxamide (PB11) on the human cell lines U87 (glioblastoma), and HeLa (cervix cancer). It was observed that this chemical was highly cytotoxic for these cells (IC50s < 50 nM). In addition, even 40 nM PB11 induced the classical apoptotic symptoms of DNA fragmentation and nuclear condensation. The increase of caspase-3 and -9 activities also indicated an increased rate of apoptosis, which was further confirmed via Western blotting analysis of apoptosis-associated proteins. Accordingly, PB11 treatment up-regulated the cellular levels of caspase-3 and cytochrome-c, whereas it down-regulated PI3K and AKT. These results suggest that PB11 induces cytotoxicity and apoptosis in cancer cells by suppressing the PI3K/AKT signaling pathways and, thus, may serve as an anti-cancer therapeutic.

scholarly journals Anti-proliferative and apoptotic effect of tetrahydrobenzo[h]quinoline on MCF-7 human breast cancer cell

2021 ◽  
Author(s):  
Maryam Ghaffari ◽  
Dariush Shanehbandi ◽  
Solmaz Sarhadi ◽  
Mina Hanifeh Ahagh ◽  
Mahsa Maleki Moghaddam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Expression Level ◽  
Caspase 8 ◽  
Human Breast ◽  
Caspase 9 ◽  
Anti Cancer ◽  
Apoptotic Effect ◽  
Mcf 7

Background: Quinoline and its derivatives display various biological activities based on versatility in designing a new drug class for medicinal applications. Hence, synthesizing innovative and varied derivatives of quinoline has gained considerable attention among chemists and biologists. This study evaluated the anti-proliferative and apoptotic effect of tetrahydrobenzo[h]quinoline on Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells. Methods: The anti-proliferative effect of tetrahydrobenzo[h]quinoline was studied via MTT [3 0-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assays. A quantitative and qualitative study of apoptosis was carried out via flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Quantitative real-time PCR (qPCR) and immunoblotting analysis were employed to identify the expression level of genes and proteins involved in the apoptosis signaling pathway. Results: The synthesized compound reduced 50% of cell growth at concentrations of 10 and 7.5 µM during 24 and 48h, respectively, and induced apoptosis up to 30% in MCF-7 cancer cells. Regarding the gene expression level, Bcl-2 displayed considerable alleviation, whereas Bax expression increased significantly. Despite the remarkable increase in caspase 9 expression, there was no noticeable difference in the caspase 8 expression in treated cells compared to the control group. Western blotting data showed that the protein expression level of Bcl-2, pro-caspase 8, and 9 reduced. The protein content of Bax, cleaved-caspase 8, and 9 increased significantly, of which the protein level of cleaved-caspase 9 exhibited a tremendous rise in the treated group. Conclusion: The newly synthesized tetrahydrobenzo[h]quinoline can be a promising organic compound for cancer treatment if its anti-cancer effect investigates by other types of breast cancer cells. In vivo studies should be used to investigate the anti-cancer efficiency of this compound.

scholarly journals FAK and S6K1 Inhibitor, Neferine, Dually Induces Autophagy and Apoptosis in Human Neuroblastoma Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3110 ◽  
Author(s):  
Dinh-Chuong Pham ◽  
Yu-Chuan Chang ◽  
Shian-Ren Lin ◽  
Yuh-Ming Fuh ◽  
May-Jywan Tsai ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Neuroblastoma Cells ◽  
Beclin 1 ◽  
Potential Candidate ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Anti Cancer

Human neuroblastoma cancer is the most typical extracranial solid tumor. Yet, new remedial treatment therapies are demanded to overcome its sluggish survival rate. Neferine, isolated from the lotus embryos, inhibits the proliferation of various cancer cells. This study aimed to evaluate the anti-cancer activity of neferine in IMR32 human neuroblastoma cells and to expose the concealable molecular mechanisms. IMR32 cells were treated with different concentrations of neferine, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability. In an effort to determine the molecular mechanisms in neferine-incubated IMR32 cells, cell cycle arrest, cell migration, and focal adhesion kinase (FAK), the 70-kDa ribosomal S6 kinase 1 (S6K1), poly (ADP-ribose) polymerase (PARP), caspase-3, Beclin-1, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein expressions were investigated. Neferine strongly disrupted the neuroblastoma cell growth via induction of G2/M phase arrest. Furthermore, neferine provoked autophagy and apoptosis in IMR32 cells, confirmed by p-FAK, and p-S6K1 reduction, LC3-II accumulation, Beclin-1 overexpression, and cleaved caspase-3/PARP improvement. Finally, neferine markedly retarded cell migration of neuroblastoma cancer cells. As a result, our findings for the first time showed an explicit anti-cancer effect of neferine in IMR32 cells, suggesting that neferine might be a potential candidate against human neuroblastoma cells to improve clinical outcomes with further in vivo investigation.

scholarly journals Tetrandrine inhibits colon carcinoma HT-29 cells growth via the Bcl-2/Caspase 3/PARP pathway and G1/S phase

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
JiaNan Li ◽  
QiuHong Wang ◽  
ZhiBin Wang ◽  
Na Cui ◽  
BingYou Yang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Molecular Docking ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Ht 29 ◽  
Active Caspase

Abstract Tetrandrine (Tet) bisbenzylisoquinoline alkaloids isolated from Stephania tetrandra and other related species of Menispermaceae. It has been demonstrated to have positive therapeutic effects on cardiovascular disease, hypertension, silicosis, autoimmune diseases. In recent years, some reports have shown that Tet has anticancer activity in human cancers. To explore the pharmacological activity and mechanism of Tet on colon cancer and its unique advantages as a natural product. In the present study, analyses of the cell cycle, apoptosis, targets prediction, molecular docking, and alterations in protein levels were performed to elucidate how Tet functions in colon cancer. We found that Tet robustly induced arrest at the G1 phase in colon cancer cell line HT-29. It induced HT-29 cell apoptosis in a dose-dependent manner. Similarly, analysis of protein expression levels in HT-29 cells showed down-regulation of Bcl-2, pro-caspase 3, pro-caspase 8, PARP, cyclin D1 (CCND1), cyclin-dependent kinase 4 (CDK 4), and up-regulation of Bax, active caspase 3, and active caspase 8. These results indicate that Tet induces apoptosis of colon cancer cells through the mitochondrial pathway and caspase family pathway. Molecular docking showed interaction effects and binding energy. Comparing with the CDK4 inhibitors ribociclib and palbociclib, the docking energy is similar to the docked amino acid residues. Therefore, we conclude that Tet and the CCND1/CDK4 compound could form hydrogen bonds and a stable compound structure, which can inhibit colon cancer cells proliferation by regulating CCND1/CDK4 compound and its downstream proteins phosphorylated Rb (p-Rb). In summary, Tet may be a potential drug for colon cancer therapy.

scholarly journals pERK 1/2 inhibit Caspase-8 induced apoptosis in cancer cells by phosphorylating it in a cell cycle specific manner

2013 ◽  
Vol 8 (2) ◽  
pp. 232-249 ◽  
Author(s):  
Ranadip Mandal ◽  
Monika Raab ◽  
Yves Matthess ◽  
Sven Becker ◽  
Rainald Knecht ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Caspase 8 ◽  
Specific Manner ◽  
A Cell ◽  
Induced Apoptosis ◽  
Apoptosis In Cancer Cells

Targeting Therapy for Resistant Multiple Myeloma with a Novel Inhibitor of NF-KB, NPI-1387.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 640-640
Author(s):  
Dharminder Chauhan ◽  
Ta-Hsiang Chao ◽  
Deli He ◽  
Teru Hideshima ◽  
Laurence Catley ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Caspase 3 ◽  
Luciferase Reporter ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Nuclear Condensation ◽  
Apoptotic Signaling

Abstract Transcription factor NF-KB is linked to growth and survival of multiple myeloma (MM)cells; blockade of NF-KB activity is therefore an attractive therapeutic strategy. Here we describe NPI-1387, a potent inhibitor of NF-KB activation and its effects on MM cells, including those resistant to conventional agents dexamethasone or doxorubicin. Cell-based assays were used to screen a library of 200 semi-synthetic analogs derived from the pimarane diterpene, Acanthoic acid. Among these analogs, NPI-1387 inhibited LPS-induced TNF-A synthesis in the murine macrophage-like RAW 264.7 cells most potently. Importantly, NPI-1387 reduced TNF-A-induced NF-KB activation in a HEK293 NF-KB/luciferase reporter cell line. Therefore additional studies were initiated to define the biological activities in MM. Treatment of MM cells lines (MM.1S, MM.1R, OCI-My5, OPM1, Dox-40) with NPI-1347 for 48h induces a dose-dependent significant (P &lt; 0.004) decrease in cell viability in all cell lines at pharmacologically achievable concentrations (IC50 range 25–40 micromolar). To determine whether NPI-1387-decreased cell viability is due to apoptosis, various MM cell lines were treated at their respective IC50 for 48h; harvested; and analyzed for apoptosis. NPI-1387 triggered significant apoptosis in these cells, as measured by a marked increase in nuclear condensation reflected by dense pattern of DAPI stain under phase contrast microscopy. In contrast, untreated control cells exhibited homogeneous and intact nuclei. Besides nuclear condensation, NPI-1387 triggered proteolytic cleavage of poly (ADP ribose) polymerase (PARP), a hallmark of apoptosis. Examination of purified patient MM cells demonstrated similar results. Notably, NPI-1387 decreases the viability of cells obtained from Bortezomib-refractory MM patient. In contrast, no significant toxicity of NPI-1387 was observed against peripheral blood mononuclear cells from normal healthy donors or CD138− MM patient cells. Moreover, NPI-1387 does not affect the viability of MM patient-derived bone marrow stromal cells (BMSCs). Genetic and biochemical evidence indicates that apoptosis proceeds by two major cell death pathways: an intrinsic pathway that involves mitochondrial membrane permeabilization and release of several apoptogenic factors, followed by caspase-9 activation; and an extrinsic apoptotic signaling pathway that occurs via caspase-8 activation. Both caspase-8 and caspase-9 activate downstream caspase-3. We therefore next examined whether NPI-1387 triggers extrinsic or intrinsic apoptotic signaling pathways. Our results show that NPI-1387 (25 micromolar) induces activation of caspase-8, and caspase-9, followed by caspase-3 cleavage. These data suggest that NPI-1387-triggered MM cell apoptosis predominantly proceeds via caspase-8/caspase-9&gt;&gt;&gt;&gt;caspase-3 signaling pathway. Together, these findings provide the rationale for clinical evaluation of NPI-1387 to induce MM cell killing, overcome drug-resistance, and improve patient outcome in MM.

Hydroxypheophorbide-α-mediated photodynamic therapy augmented by pretreatment with genistein inCaSkicervical cancer cells

2009 ◽  
Vol 13 (07) ◽  
pp. 842-847
Author(s):  
Jang-In Shin ◽  
Jin-Chul Ahn ◽  
Sang-Joon Lee ◽  
Ock Jin Park ◽  
Phil-Sang Chung
Keyword(s):  
Photodynamic Therapy ◽  
Er Stress ◽  
Cancer Cells ◽  
Combination Treatment ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Combined Treatment ◽  
Red Light ◽  
Caspase 8 ◽  
Induced Apoptosis

Photodynamic therapy (PDT) is a treatment for cancer involving three key components — a sensitizing compound (light) tissue, and oxygen. In this study we applied phototreatment to cancer cells with 2 J.cm-2of red light after sensitizing with 9-hydroxypheophorbide-α (9-HpbD-α), a new chlorophyll-derived photosensitizer. We have investigated the cytotoxic and apoptotic effects of 9-HpbD-α-induced PDT in cervical cancer cells, the enhancing effect of genistein in PDT, and explored the molecular mechanisms of E6 or E7 oncogenes, apoptotic signaling molecules, and ER stress. Co-treatment downregulated the transcripts of the E6*I, E6*II, and E7 oncogenes. Combined treatment with PDT and genistein showed typical apoptotic features, i.e. apoptotic bodies. To elucidate the mechanism of combination treatment-induced apoptosis, various mediators of apoptosis were investigated. Activation of caspase-8, caspase-3, and PARP were distinct after combination treatment. Furthermore, ER stress-related proteins, such as CHOP and GRP78, were activated after combination treatment. We conclude that genistein sensitizes CaSki cells to apoptosis treated with PDT by 9-HpbD-α (0.59 μg/mL) through mechanisms that involve downregulation of the E6*I, E6*II, and E7 oncogenes, activation of caspase-8 or caspase-3, and ER stress.

scholarly journals The anti-cancer drug gefitinib accelerates Fas-mediated apoptosis by enhancing caspase-8 activation in cancer cells

2019 ◽  
Vol 44 (6) ◽  
pp. 435-440 ◽  
Author(s):  
Yuto Sekiguchi ◽  
Mayuka Yamada ◽  
Takuya Noguchi ◽  
Chise Noomote ◽  
Mei Tsuchida ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Drug ◽  
Caspase 8 ◽  
Anti Cancer

Cadmium inhibits both intrinsic and extrinsic apoptotic pathways in renal mesangial cells

2006 ◽  
Vol 290 (5) ◽  
pp. F1074-F1082 ◽  
Author(s):  
C. Geeth Gunawardana ◽  
Raul E. Martinez ◽  
Weiqun Xiao ◽  
Douglas M. Templeton
Keyword(s):  
Caspase 3 ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Experimental Models ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Nuclear Condensation ◽  
Tnf Α ◽  
Convergence Point ◽  
Apoptotic Pathways

Cadmium is a potent nephrotoxin that has been shown to induce apoptosis in some cells but also to prevent it under certain circumstances. In several clinical situations and experimental models of injury to the renal glomerulus, pathological proliferation of mesangial cells is followed by resolution involving mesangial cell apoptosis. We investigated the effects of Cd2+ on rat mesangial cells induced to undergo apoptosis through either the extrinsic receptor-mediated pathway or the intrinsic mitochondrial-dependent pathway. Camptothecin initiated the intrinsic pathway with activation of caspase-9 and caspase-dependent cleavage of procaspase-3. Tumor necrosis factor-α (TNF-α) initiated caspase-8 activity and cleavage of pro-caspase-3 at the convergence point of the two pathways. However, pro-caspase-8 levels were low, and caspase-9 was also activated in response to TNF-α, characteristic of what have been termed type II cells. With both TNF-α and camptothecin, concurrent exposure to 10 μM CdCl2 suppressed DNA laddering, nuclear condensation, and pro-caspase-3 cleavage. It also decreased activity of both caspase-8 and caspase-9, prevented caspase-8-dependent cleavage of the proapoptotic factor Bid, and suppressed release of cytochrome c from mitochondria. At this 10-μM concentration, Cd2+ was unique among a number of metal ions in preventing DNA fragmentation. We conclude that Cd2+ is anti-apoptotic in rat mesangial cells, acting by a mechanism that may involve general caspase inhibition. This may have consequences for the resolution of nephritis in situations of mesangial cell hyperproliferation.

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