scholarly journals Toxicity and Apoptosis Related Effects of Benzimidazo [3,2-α] Quinolinium Salts Upon Human Lymphoma Cells

2017 ◽  
Vol 11 (1) ◽  
pp. 54-65 ◽  
Author(s):  
Christian Vélez ◽  
Jessica Soto ◽  
Karoline Ríos ◽  
Luz Silva ◽  
Wigberto Hernandez ◽  
...  
Keyword(s):  
Ros Generation ◽  
Fluorescence Staining ◽  
Cycle Arrest ◽  
Effector Caspase ◽  
Anti Cancer ◽  
Independent Mechanism ◽  
Human Lymphoma ◽  
Apoptosis Inducing Factor ◽  
Related Proteins ◽  
Quinolinium Salts

Objectives: The present study evaluates novel cationic quinoline derivatives known as benzimidazo[3,2-a]quinolinium salts (BQS) named NBQ-48 and ABQ-48 that have structural similarities to known anti-cancer substances such as ellipticine and berberine. Methods: Toledo human lymphoma (ATCC CRL2631) cells were treated for 24 to 48 hours. Apoptosis related endpoints such as cell cycle arrest, mitochondrial damage, RNS and ROS generation and the activity of several apoptosis related proteins such as caspases and apoptosis inducing factor (AIF) were studied using fluorescence staining and western blot respectively. Results: Results indicated a higher toxicity from the amino substituted ABQ-48 versus the NBQ-48 (GI50’s of 50uM versus 100uM respectively). Both compounds induced cell death through various apoptosis related endpoints including a decrease in mitochondrial membrane potential with an increase in ROS and activation of the effector caspase 3. Interestingly, AIF release was observed on cells treated with the amino substituted ABQ-48 but not on the nitro substituted NBQ-48 samples suggesting a caspase independent mechanism for ABQ-48. Conclusions: The results obtained presents the toxic effects of two novel benzimidazo[3,2-a]quinolinium salts in human lymphoma tumor cells. The identified mechanism of action includes multiple apoptosis related effects. Furthermore the data presents a clear variation in caspase dependent or independent mechanism for each compound.

Molecular Mechanisms of Thymoquinone as Anticancer agent

2020 ◽  
Vol 23 ◽  
Author(s):  
Fatma Ismail Alhmied ◽  
Ali Hassan Alammar ◽  
Bayan Mohammed Alsultan ◽  
Marooj Alshehri ◽  
Faheem Hyder Pottoo
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Human Breast Cancer ◽  
Phase Cell ◽  
Cycle Phase ◽  
Human Breast ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
Anti Cancer

Abstract:: Thymoquinone (TQ), the bioactive constituent of Nigella Sativa seeds is a well-known natural compound for the management of several types of cancers. The anti-cancer properties of thymoquinone are thought to be operated via intervening with various oncogenic pathways including cell cycle arrest, prevention of inflammation and oxidative stress, induction of invasion, metastasis, inhibition of angiogenesis, and apoptosis. As well as up-regulation and down-regulation of specific tumor suppressor genes and tumor promoting genes, respectively. Proliferation of various tumor cells is inhibited by TQ via induction of cell cycle arrest, disruption of the microtubule organization, and down regulating cell survival protein expression. TQ induces G1 phase cell cycle arrest in human breast cancer, colon cancer and osteosarcoma cells through inhibiting the activation of cyclin E or cyclin D and up-regulating p27and p21 a cyclin dependent kinase (Cdk) inhibitor. TQ concentration is a significant factor in targeting a particular cell cycle phase. While high concentration of TQ induced G2 phase arrest in human breast cancer (MCF-7) cells, low concentration causes S phase arrest. This review article provides mechanistic insights into the anti-cancer properties of thymoquinone.

Animal Venoms have Potential to Treat Cancer

2019 ◽  
Vol 18 (30) ◽  
pp. 2555-2566 ◽  
Author(s):  
Bhaswati Chatterjee
Keyword(s):  
Cancer Therapeutics ◽  
Sea Anemones ◽  
Anticancer Activities ◽  
Inhibition Of Proliferation ◽  
Cycle Arrest ◽  
Venomous Animals ◽  
Anti Cancer ◽  
Cancerous Cells ◽  
Animal Venoms ◽  
Proteins And Peptides

The resistance to chemotherapeutics by the cancerous cells has made its treatment more complicated. Animal venoms have emerged as an alternative strategy for anti-cancer therapeutics. Animal venoms are cocktails of complex bioactive chemicals mainly disulfide-rich proteins and peptides with diverse pharmacological actions. The components of venoms are specific, stable, and potent and have the ability to modify their molecular targets thus making them good therapeutics candidates. The isolation of cancer-specific components from animal venoms is one of the exciting strategies in anti-cancer research. This review highlights the identified venom peptides and proteins from different venomous animals like snakes, scorpions, spiders, bees, wasps, snails, toads, frogs and sea anemones and their anticancer activities including inhibition of proliferation of cancer cells, their invasion, cell cycle arrest, induction of apoptosis and the identification of involved signaling pathways.

Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

2020 ◽  
Vol 15 (6) ◽  
pp. 482-491 ◽  
Author(s):  
Milena Kostadinova ◽  
Milena Mourdjeva
Keyword(s):  
Cancer Cells ◽  
Small Population ◽  
Tumor Formation ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
New Methods ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

scholarly journals ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts

2021 ◽  
Vol 22 (9) ◽  
pp. 4797
Author(s):  
So Young Kim ◽  
Cheol Park ◽  
Min Yeong Kim ◽  
Seon Yeong Ji ◽  
Hyun Hwangbo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Ethanol Extract ◽  
Pharmacological Intervention ◽  
Ros Generation ◽  
Apoptosis Pathway ◽  
Invasion And Migration ◽  
Intrinsic Apoptosis Pathway ◽  
Anti Cancer ◽  
Coptidis Rhizoma ◽  
Hep3b Cells

Coptidis Rhizoma is the dried rhizome from the Coptis chinensis Franch. that has been shown to have a number of beneficial pharmacological properties including antioxidant, anti-inflammatory, and anti-cancer effects. However, the anti-cancer effects of Coptidis Rhizoma on hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the anti-cancer properties of Coptidis Rhizoma ethanol extract (CR) in HCC Hep3B cells and in a xenograft mouse model. Our results showed that the CR significantly inhibited cell growth and induced apoptosis in Hep3B cells through increased expression of Bcl-2 associated x-protein (Bax) and cleavage of poly-ADP ribose polymerase (PARP), reduced expression of Bcl-2, and activated caspases. CR also increased the generation of intracellular reactive oxygen species (ROS), which caused a loss of mitochondrial membrane potential (MMP, ΔΨm) and activation of the mitochondria-mediated intrinsic apoptosis pathway. Moreover, N-acetylcysteine (NAC), a ROS inhibitor, markedly blocked the effects of CR on apoptotic pathways. CR also induced the expression of light chain 3 (LC3)-I/II, a key autophagy regulator, whereas CR-mediated autophagy was significantly suppressed by NAC. In addition, pre-treatment with NAC perfectly attenuated the inhibition of cell invasion and migration of CR-stimulated Hep3B cells. Furthermore, oral administration of CR suppressed Hep3B tumor growth in xenograft mice without toxicity, alterations to body weight, or changes in hematological and biochemical profiles. Taken together, our findings suggest that CR has anti-tumor effects that result from ROS generation, and may be a potential pharmacological intervention for HCC.

scholarly journals Design, Synthesis and Pharmacological Evaluation of Three Novel Dehydroabietyl Piperazine Dithiocarbamate Ruthenium (II) Polypyridyl Complexes as Potential Antitumor Agents: DNA Damage, Cell Cycle Arrest and Apoptosis Induction

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1453
Author(s):  
Haoran Wang ◽  
Jianhua Wei ◽  
Hong Jiang ◽  
Ye Zhang ◽  
Caina Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Antitumor Agents ◽  
Mechanistic Study ◽  
Ros Generation ◽  
Polypyridyl Complexes ◽  
Expression Levels ◽  
Cycle Arrest ◽  
Study Results

The use of cisplatin is severely limited by its toxic side-effects, which has spurred chemists to employ different strategies in the development of new metal-based anticancer agents. Here, three novel dehydroabietyl piperazine dithiocarbamate ruthenium (II) polypyridyl complexes (6a–6c) were synthesized as antitumor agents. Compounds 6a and 6c exhibited better in vitro antiproliferative activity against seven tumor cell lines than cisplatin, they displayed no evident resistance in the cisplatin-resistant cell line A549/DPP. Importantly, 6a effectively inhibited tumor growth in the T-24 xenograft mouse model in comparison with cisplatin. Gel electrophoresis assay indicated that DNA was the potential targets of 6a and 6c, and the upregulation of p-H2AX confirmed this result. Cell cycle arrest studies demonstrated that 6a and 6c arrested the cell cycle at G1 phase, accompanied by the upregulation of the expression levels of the antioncogene p27 and the down-regulation of the expression levels of cyclin E. In addition, 6a and 6c caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-9, cytochrome c, intracellular Ca2+ release, reactive oxygen species (ROS) generation and the downregulation of Bcl-2. These mechanistic study results suggested that 6a and 6c exerted their antitumor activity by inducing DNA damage, and consequently causing G1 stage arrest and the induction of apoptosis.

scholarly journals Differential Mechanisms of Cell Death Induced by HDAC Inhibitor SAHA and MDM2 Inhibitor RG7388 in MCF-7 Cells

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 8 ◽  
Author(s):  
Umamaheswari Natarajan ◽  
Thiagarajan Venkatesan ◽  
Vijayaraghavan Radhakrishnan ◽  
Shila Samuel ◽  
Appu Rathinavelu
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Hdac Inhibitor ◽  
The Other ◽  
Combination Treatments ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Mcf 7

Gene expression is often altered by epigenetic modifications that can significantly influence the growth ability and progression of cancers. SAHA (Suberoylanilide hydroxamic acid, also known as Vorinostat), a well-known Histone deacetylase (HDAC) inhibitor, can stop cancer growth and metastatic processes through epigenetic alterations. On the other hand, Letrozole is an aromatase inhibitor that can elicit strong anti-cancer effects on breast cancer through direct and indirect mechanisms. A newly developed inhibitor, RG7388 specific for an oncogene-derived protein called MDM2, is in clinical trials for the treatment of various cancers. In this paper, we performed assays to measure the effects of cell cycle arrest resulting from individual drug treatments or combination treatments with SAHA + letrozole and SAHA + RG7388, using the MCF-7 breast cancer cells. When SAHA was used individually, or in combination treatments with RG7388, a significant increase in the cytotoxic effect was obtained. Induction of cell cycle arrest by SAHA in cancer cells was evidenced by elevated p21 protein levels. In addition, SAHA treatment in MCF-7 cells showed significant up-regulation in phospho-RIP3 and MLKL levels. Our results confirmed that cell death caused by SAHA treatment was primarily through the induction of necroptosis. On the other hand, the RG7388 treatment was able to induce apoptosis by elevating BAX levels. It appears that, during combination treatments, with SAHA and RG7388, two parallel pathways might be induced simultaneously, that could lead to increased cancer cell death. SAHA appears to induce cell necroptosis in a p21-dependent manner, and RG7388 seems to induce apoptosis in a p21-independent manner, outlining differential mechanisms of cell death induction. However, further studies are needed to fully understand the intracellular mechanisms that are triggered by these two anti-cancer agents.

scholarly journals Induction of cell death in prostate cancer cells by escopoletin, a promising treatment strategy

2015 ◽  
Vol 10 (3) ◽  
pp. 500 ◽  
Author(s):  
Da Chen ◽  
Xiao-Yi Zhang ◽  
Fa-Zhu Zheng ◽  
Hai-Tao Wang ◽  
Jian-Liang Cai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Antioxidant Activities ◽  
Apoptotic Cell ◽  
Annexin V ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Enhanced Expression ◽  
Promising Treatment ◽  
Du145 Cells

<p>Escopoletin, a phenolic compound belonging to anthocyanin family shows promising antioxidant activities. In the present study, anti-cancer effects of escopoletin treatment in DU145 cells were investigated. The sulphorhodamine-B staining and annexin V and propidium iodide were respectively used for the analysis of cell viability and death. The results revealed a significantly higher cytotoxicity by escopoletin that caused cell death in DU145 cells. Escopoletin treatment in DU145 cells markedly inhibited cell growth through non-apoptotic cell death and induced significant reactive oxygen species (ROS) production. It also induced G1 cell cycle arrest and cyclin D1 accumulation through the enhanced expression of p21. However, the effect of escopoletin on DU145 cells was reversed by pretreatment with glutathione antioxidant. This suggests that escopoletin induced generation of ROS is responsible for the increased cytotoxicity in DU145 cells. Thus, escopoletin exhibits potential therapeutic efficacy for the treatment of prostate cancer.</p><p> </p>

scholarly journals Pivotal Role of Iron Homeostasis in the Induction of Mitochondrial Apoptosis by 6-Gingerol Through PTEN Regulated PD-L1 Expression in Embryonic Cancer Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Nipin Sp ◽  
Dong Young Kang ◽  
Eun Seong Jo ◽  
Jin-Moo Lee ◽  
Se Won Bae ◽  
...  
Keyword(s):  
Cell Death ◽  
Iron Homeostasis ◽  
Reactive Oxygen Species Generation ◽  
Cancer Recurrence ◽  
Cancer Type ◽  
Molecular Signaling ◽  
Cellular Processes ◽  
P53 Signaling ◽  
Cycle Arrest ◽  
Anti Cancer

Embryonic cancer stem cells (CSCs) can differentiate into any cancer type. Targeting CSCs with natural compounds is a promising approach as it suppresses cancer recurrence with fewer adverse effects. 6-Gingerol is an active component of ginger, which exhibits well-known anti-cancer activities. This study determined the mechanistic aspects of cell death induction by 6-gingerol. To analyze cellular processes, we used Western blot and real-time qPCR for molecular signaling studies and conducted flow cytometry. Our results suggested an inhibition of CSC marker expression and Wnt/β-catenin signaling by 6-gingerol in NCCIT and NTERA-2 cells. 6-Gingerol induced reactive oxygen species generation, the DNA damage response, cell cycle arrest, and the intrinsic pathway of apoptosis in embryonic CSCs. Furthermore, 6-gingerol inhibited iron metabolism and induced PTEN, which both played vital roles in the induction of cell death. The activation of PTEN resulted in the inhibition of PD-L1 expression through PI3K/AKT/p53 signaling. The induction of PTEN also mediated the downregulation of microRNAs miR-20b, miR-21, and miR-130b to result in PD-L1 suppression by 6-gingerol. Hence, 6-gingerol may be a promising candidate to target CSCs by regulating PTEN-mediated PD-L1 expression.

Corrigendum

2021 ◽  
Vol 21 (17) ◽  
pp. 2464-2464
Keyword(s):  
Science And Technology ◽  
Scientific Research ◽  
Uttar Pradesh ◽  
Research Project ◽  
Hpv E6 ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Cervical Cancer Cells ◽  
E6 And E7 ◽  
Funding Information

Minor changes are required in the Funding information and the acknowledgement for the article entitled “Organosulphur Compounds Induce Apoptosis and Cell Cycle Arrest in Cervical Cancer Cells via Downregulation of HPV E6 and E7 Oncogenes” in “Anti-Cancer Agents in Medicinal Chemistry, 2021, Vol. 21, No. 3, pp. 393-405.” The correct Funding information and Acknowledgement is given below: FUNDING: This project was funded by the Council of Science and Technology (CST), Lucknow, Uttar Pradesh, India (Sanction No. CST/374). The financial support during this research was also provided by the Deanship of Scientific Research, King Khalid University, Abha, Saudia Arabia through the General Research Project under grant number R.G.P. 01/48/42. ACKNOWLEDGEMENT: IAA is greatly thankful to the Council of Science and Technology (CST), Uttar Pradesh, India, for providing him project as a Principal Investigator. Authors would also like to acknowledge the support of the King Khalid University through the General Research Project under grant number R.G.P. 01/48/42. under the Deanship of Scientific Research, King Khalid University, Abha, Saudia Arabia

scholarly journals MiR-657/ATF2 Signaling Pathway Has a Critical Role in Spatholobus suberectus Dunn Extract-Induced Apoptosis in U266 and U937 Cells

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 150 ◽  
Author(s):  
Hyun Lim ◽  
Moon Park ◽  
Changmin Kim ◽  
Beomku Kang ◽  
Hyo-Sook Song ◽  
...  
Keyword(s):  
Er Stress ◽  
Critical Role ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Parp Cleavage ◽  
Dependent Manner ◽  
U937 Cells ◽  
Anti Cancer ◽  
Spatholobus Suberectus ◽  
Induced Apoptosis ◽  
Related Proteins

Though Spatholobus suberectus Dunn (SSD) has been reported to have anti-virus, anti-osteoclastogenesis, and anti-inflammation activities, its underlying anti-cancer mechanism has never been elucidated in association with the role of miR-657 in endoplasmic reticulum (ER) stress-related apoptosis to date. SSD treatment exerted cytotoxicity in U266 and U937 cells in a dose-dependent manner. Also, apoptosis-related proteins such as PARP, procaspase-3, and Bax were regulated by SSD treatment. Furthermore, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed that a number of apoptotic bodies were increased by SSD. Interestingly, the ER stress-related proteins such as p-ATF2 and CHOP were elevated by SSD. Interestingly, reactive oxygen species (ROS) generation and cytotoxicity by SSD treatment were significantly reduced by N-Acetyl-L-cysteine (NAC). Among the microRNAs (miRNAs) regulated by SSD treatment, miR-657 was most significantly reduced by SSD treatment. However, an miR-657 mimic reversed SSD-induced apoptosis by the attenuation of the expression of p-ATF2, CHOP, and PARP cleavage. Overall, these findings provide scientific evidence that miR657 is an onco-miRNA targeting the ER stress signal pathway and SSD induces apoptosis via the inhibition of miR-657, ROS, and the activation of p-ATF2 and CHOP as a potent anti-cancer agent for myeloid-originated hematological cancer.

Sign in / Sign up

Export Citation Format

Share Document