The Cell Cycle, Cyclins, Checkpoints and Cancer

Cancer is a serious problem affecting the health of human and isone of the leading cause of mortality worldwide. A normal cell undergoes regulated cell division, differentiation and apoptosis (programmed cell death). When normal cell has lost the usual control over their division, differentiation and apoptosis they become tumor cells. Cancer arises mainly from mutations in somatic cells. Maintenance of genomic integrity is a pre-requisite for a safe and long lasting life. For this purpose, cell has quality control points, referred as checkpoints. The different mechanisms and multiple researchers involved in the field necessiatean understanding of the molecular mechanism to classify tumor and to assess the risk and treatment of disease. Certain therapeutic strategies exist and many more need to be explored. Different experimental therapies are currently in clinical trials and are raising hopes that a new class of anti-cancer drug may soon be available.

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Design, Synthesis and In Vitro Anti-Cancer Evaluation of Novel Derivatives of 2-(2-Methyl-1,5-diaryl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3- yl)acetamide

Medicinal Chemistry ◽

10.2174/1573406415666190425153717 ◽

2020 ◽

Vol 16 (3) ◽

pp. 340-349

Author(s):

Ebrahim S. Moghadam ◽

Farhad Saravani ◽

Ernest Hamel ◽

Zahra Shahsavari ◽

Mohsen Alipour ◽

...

Keyword(s):

Cell Cycle ◽

Peripheral Neuropathy ◽

Cell Line ◽

Normal Cell ◽

Caspase 3 ◽

Annexin V ◽

Normal Cell Line ◽

Anti Cancer ◽

Mcf 7

Objective: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage. Methods: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay. Results: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100 μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3. Conclusion: Newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial.

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Facile Synthetic Protocols for the preparation of New Impurities in Pemetrexed Disodium Heptahydrate as an Anti-Cancer Drug

Current Organic Synthesis ◽

10.2174/1570179418666210114145914 ◽

2021 ◽

Vol 18 ◽

Author(s):

Rama Mohana Reddy Jaggavarapu ◽

Venkatanarayana Muvvala ◽

Ghojala Venkatareddy ◽

Ravi Kumar Cheedarala

Keyword(s):

Quality Control ◽

Spectral Analysis ◽

1H Nmr ◽

Structure Elucidation ◽

Research Work ◽

Synthetic Methods ◽

Cancer Drug ◽

The Novel ◽

Anti Cancer ◽

Pemetrexed Disodium

: A facile synthetic protocols were employed to prepare process-related impurities associated with the synthesis of pemetrexed disodium heptahydrate, Alimta. The research work is described for the development of the novel synthetic methods and their structure elucidation of Pemetrexed glutamide, N-methyl pemetrexed, and N-methyl pemetrexed glutamide impurities. The listed impurities were deduced through spectral analysis such as 1H-NMR, 13CNMR, and HRMS. The target compounds can be used as the reference substances for the quality control.

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Chemical dissection of the cell cycle: probes for cell biology and anti-cancer drug development

Cell Death and Disease ◽

10.1038/cddis.2014.420 ◽

2014 ◽

Vol 5 (10) ◽

pp. e1462-e1462 ◽

Cited By ~ 37

Author(s):

S Senese ◽

Y C Lo ◽

D Huang ◽

T A Zangle ◽

A A Gholkar ◽

...

Keyword(s):

Cell Cycle ◽

Drug Development ◽

Cell Biology ◽

Cancer Drug ◽

Anti Cancer

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BIOBOARD

Asia-Pacific Biotech News ◽

10.1142/s0219030313000700 ◽

2013 ◽

Vol 17 (10n11) ◽

pp. 4-16

Keyword(s):

Early Stage ◽

Cancer Drug ◽

Blood Proteins ◽

University Of Minnesota ◽

Early Stage Lung Cancer ◽

Life And Death ◽

New Class ◽

Prosthetic Limbs ◽

Anti Cancer ◽

3D Printed

AUSTRALIA – Centipede venom could lead to new class of pain drug. AUSTRALIA – Artificial nerves in prosthetic limbs to restore touch: study. SINGAPORE – Singapore scientists lead in the discovery of gene responsible for fatal drug allergy. SINGAPORE – ‘Jekyll-and-Hyde’ protein determines life and death of cancer cells. SINGAPORE – A*STAR researchers create novel assay to test for epigenetic abnormalities in pre-implanted mice embryos. SINGAPORE – New hydrogel from IBN and IBM improves delivery of anti-cancer drug. EUROPE – Novel family of natural products antibiotics with broad spectrum against Gram-negative pathogens. NEPAL – Blood proteins could help monitor malnutrition. UK – Developing world faces breast cancer surge, study suggests. US – Positive signs for malaria vaccine based on GM parasite. US – Could one cancer test find unrelated tumors? US – Study suggests blood test can differentiate between benign lung nodules and early stage lung cancer. US – New data obtained from Parkinson's disease program. US – Research study on PAZ320 initiated at University of Minnesota. US – 3D printed structures reveal bacterial ‘chit-chat’.

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Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms19092739 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2739 ◽

Cited By ~ 12

Author(s):

Sang-A Kim ◽

Ok-Hwa Kang ◽

Dong-Yeul Kwon

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Annexin V ◽

Phase Cell ◽

Cancer Drug ◽

Dapi Staining ◽

Cycle Arrest ◽

Apoptosis Protein ◽

Anti Cancer ◽

Cancer Agent

Cryptotanshinone (CTT) is a natural product and a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miltiorrhizabunge. Notably, CTT has a variety of anti-cancer actions, including the activation of apoptosis, anti-proliferation, and reduction in angiogenesis. We further investigated the anti-cancer effects of CTT using MTS, LDH, and Annexin V assay, DAPI staining, cell cycle arrest, and Western blot analysis in NSCLC cell lines. NSCLC cells treated with CTT reduced cell growth through PI3K/Akt/GSK3β pathway inhibition, G0/G1 cell cycle arrest, and the activation of apoptosis. CTT induced an increase of caspase-3, caspase-9, poly-ADP-ribose polymerase (PARP), and Bax, as well as inhibition of Bcl-2, survivin, and cellular-inhibitor of apoptosis protein 1 and 2 (cIAP-1 and -2). It also induced G0/G1 phase cell cycle arrest by decreasing the expression of the cyclin A, cyclin D, cyclin E, Cdk 2, and Cdk 4. These results highlight anti-proliferation the latent of CTT as natural therapeutic agent for NSCLC. Therefore, we investigated the possibility of CTT as an anti-cancer agent by comparing with GF, which is a representative anti-cancer drug.

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pH-Sensitive Dendrimersomes of Hybrid Triazine-Carbosilane Dendritic Amphiphiles-Smart Vehicles for Drug Delivery

Nanomaterials ◽

10.3390/nano10101899 ◽

2020 ◽

Vol 10 (10) ◽

pp. 1899 ◽

Cited By ~ 1

Author(s):

Evgeny Apartsin ◽

Nadezhda Knauer ◽

Valeria Arkhipova ◽

Ekaterina Pashkina ◽

Alina Aktanova ◽

...

Keyword(s):

Drug Delivery ◽

Drug Loading ◽

Drug Carriers ◽

Ph Sensitive ◽

Cancer Drug ◽

Smart Vehicles ◽

New Class ◽

Self Assembling ◽

Anti Cancer ◽

Cancer Drug Delivery

Supramolecular constructions of amphiphilic dendritic molecules are promising vehicles for anti-cancer drug delivery due to the flexibility of their architecture, high drug loading capacity and avoiding off-target effects of a drug. Herein, we report a new class of amphiphilic dendritic species—triazine-carbosilane dendrons readily self-assembling into pH-sensitive dendrimersomes. The dendrimersomes efficiently encapsulate anticancer drugs doxorubicin and methotrexate. Chemodrug-loaded dendrimersomes have dose-related cytotoxic activity against leukaemia cell lines 1301 and K562. Our findings suggest that triazine-carbosilane dendrimersomes are prospective drug carriers for anti-cancer therapy.

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Design, Synthesis and Bioactivity Evaluation of Novel Chalcone Derivatives Possessing Tryptophan Moiety with Dual Activities of Anti-cancer and Partially Restoring the Proliferation of Normal Kidney Cells Pre-treated with Cisplatin

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666211021134626 ◽

2021 ◽

Vol 21 ◽

Author(s):

Meng He ◽

Mingjun Yu ◽

Chao Li ◽

Xiaoming Meng ◽

Jiamin Su ◽

...

Keyword(s):

Cell Cycle ◽

Cell Line ◽

Normal Cell ◽

Kidney Cells ◽

Normal Kidney ◽

Normal Cell Line ◽

Chalcone Derivatives ◽

Anti Cancer ◽

Anti Inflammatory ◽

Cancer Activity

Background: Chalcone is a broad-spectrum natural product with anti-cancer and anti-inflammatory activities. However, low potency, low selectivity, and serious side effects limit its druggability. L-Tryptophan is an essential precursor molecule of an anti-cancer active substance. Also, the indole moiety inhibits the proliferation of tumor cells by binding to colchicine sites. A decrease in kidney cell activity caused by kidney inflammation is the primary side effect of cancer therapy. Objective: The purpose of this work was to design, synthesize, and perform bioactivity evaluation of novel chalcone derivatives possessing tryptophan moiety with dual activities of anti-cancer and partially restoring the proliferation of normal kidney cells pre-treated with cisplatin. Methods: A series of novel chalcone derivatives possessing tryptophan moiety (5a-5g, 6a-6o) were designed, synthesized, and evaluated for anti-cancer activity against four cancer cell lines (gastric (HGC-27), colon (HCT-116), prostate (PC-3), and lung (A549)), and a human normal cell line (gastric mucosal epithelial (GES-1)). The activity of restoring the proliferation of normal kidney cells pre-treated with cisplatin was evaluated by MTT assay. Cell cycle, apoptosis, and apoptosis proteins (Bax and Bcl-2) were used to evaluate the anti-cancer mechanism of the most potent compound. Moreover, a docking study was performed to explain the high anti-cancer activity of 6n. The expressions of TNF-α, IL-6, and MCP-1 were detected by ELISA. Results: Most of the compounds exhibited high anti-cancer activity against the HGC-27 cell line and exhibited low toxicity against the normal cell line. Based on three rounds of a structure optimization, 6n was discovered as the most potent compound against HGC-27 cells with an IC50 value of 2.02 μM and an SI value of 28.47. Further studies demonstrated that 6n could induce cell cycle arrest at the G2/M phase and the apoptosis of the HGC-27 cell line by reducing the expression of Bcl-2 and improving the expression level of Bax. Molecular docking result displayed 6n bound to the colchicine site. At the same time, 6n also exhibited moderate activity of restoring the proliferation of normal kidney cells pre-treated with cisplatin by reducing the expression of inflammatory substances. Conclusion: Our findings collectively suggested that 6n should be further studied as a potential anti-cancer agent that could partially restore the proliferation of normal kidney cells pre-treated with cisplatin in gastric cancer patients by an anti-inflammatory pathway.

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