Apoptotic Pathway

2021 ◽  
pp. 290-311
Author(s):  
Durdana Yasin ◽  
Md Zafaryab ◽  
Khalid Umar Fakhri ◽  
Shaheen Husain ◽  
Bushra Afzal ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Treatment ◽  
Tissue Homeostasis ◽  
The Novel ◽  
Down Regulation ◽  
Apoptotic Pathway ◽  
Biochemical Characteristics ◽  
Novel Drugs ◽  
Natural Mechanism ◽  
Apoptotic Factors

Cancer is a major killer disease caused by uncontrolled growth and invasion of cells. Apoptosis is the cell's natural mechanism of death, which maintains tissue homeostasis. Any mutation that disturbs the apoptotic pathway leads to deregulated proliferation, resistance, and evasion of apoptosis. This evasion is one of the hallmarks of malignant developments. Apoptosis takes place via two distinct pathways i.e. the intrinsic and the extrinsic pathways. These pathways use cleaved caspases to execute apoptosis which in turn cleave many downstream proteins to kill the cells. They can also be inhibited through various means that include up-regulation of anti-apoptotic and down-regulation of pro-apoptotic factors. The authors here aim to impart a comprehensive understanding of the biochemical characteristics of these pathways that render scientists target these pathways and assess apoptosis restoring abilities of the novel drugs and natural products for cancer treatment.

scholarly journals Natural products with therapeutic potential in melanoma metastasis

2015 ◽  
Vol 32 (8) ◽  
pp. 1170-1182 ◽  
Author(s):  
A. AlQathama ◽  
J. M. Prieto
Keyword(s):  
Natural Products ◽  
Cancer Treatment ◽  
Therapeutic Potential ◽  
Melanoma Cells ◽  
Mechanisms Of Action ◽  
Melanoma Metastasis ◽  
Pharmacological Effects ◽  
Cytotoxic Compounds

Natural products continue to provide lead cytotoxic compounds for cancer treatment but less attention has been given to antimigratory compounds. We here systematically and critically survey more than 30 natural products with direct in vitro and in vivo pharmacological effects on migration and/or metastasis of melanoma cells and chart the mechanisms of action for this underexploited property.

scholarly journals Preparation of Cyclic Peptide Alkaloids Containing Functionalized Tryptophan Residues

2006 ◽  
Vol 1 (10) ◽  
pp. 1934578X0600101
Author(s):  
Alexander K. L. Yuen ◽  
Craig A. Hutton
Keyword(s):  
Natural Products ◽  
Cyclic Peptide ◽  
The Novel ◽  
Diazonamide A ◽  
The Core ◽  
Tryptophan Residues ◽  
Novel Methods

This review covers the synthesis of various cyclic peptide natural products possessing highly functionalized tryptophan residues, focusing on the examples of diazonamide A, the TMC-95 compounds, the celogentin/moroidin family and the complestatin/chloropeptin system. Recent efforts toward the preparation of these modified-tryptophan-containing peptides will be outlined, focusing primarily on the novel methods for the assembly of the highly functionalized indole/tryptophan moieties at the core of these structures.

scholarly journals Natural Products, Traditional Uses and Pharmacological Activities of the Genus Biebersteinia (Biebersteiniaceae)

Plants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 595 ◽  
Author(s):  
Benyin Zhang ◽  
Xiaona Jin ◽  
Hengxia Yin ◽  
Dejun Zhang ◽  
Huakun Zhou ◽  
...  
Keyword(s):  
Natural Products ◽  
Molecular Mechanisms ◽  
Chemical Properties ◽  
Pharmacological Properties ◽  
Pharmacological Activities ◽  
Drug Discovery And Development ◽  
Chemical Structures ◽  
Traditional Uses ◽  
Novel Drugs ◽  
Major Chemical

Medicinal plants have been known as a rich source of natural products (NPs). Due to their diverse chemical structures and remarkable pharmacological activities, NPs are regarded as important repertoires for drug discovery and development. Biebersteinia plant species belong to the Biebersteiniaceae family, and have been used in folk medicines in China and Iran for ages. However, the chemical properties, bioactivities and modes of action of the NPs produced by medicinal Biebersteinia species are poorly understood despite the fact that there are only four known Biebersteinia species worldwide. Here, we reviewed the chemical classifications and diversity of the various NPs found in the four known Biebersteinia species. We found that the major chemical categories in these plants include flavonoids, alkaloids, phenylpropanoids, terpenoids, essential oils and fatty acids. We also discussed the anti-inflammatory, analgesic, antibacterial, antioxidant, antihypertensive and hypoglycemic effects of the four Biebersteinia species. We believe that the present review will facilitate the exploration of traditional uses and pharmacological properties of Biebersteinia species, extraction of the NPs and elucidation of their molecular mechanisms, as well as the development of novel drugs based on the reported properties and mode-of-action.

Multiple drug-loaded electrospun PLGA/gelatin composite nanofibers encapsulated with mesoporous ZnO nanospheres for potential postsurgical cancer treatment

RSC Advances ◽  
2014 ◽  
Vol 4 (53) ◽  
pp. 28011-28019 ◽  
Author(s):  
Junchao Wei ◽  
Jun Hu ◽  
Ming Li ◽  
Yong Chen ◽  
Yiwang Chen
Keyword(s):  
Cancer Treatment ◽  
Composite Nanofibers ◽  
Multiple Drug ◽  
The Novel ◽  
Mesoporous Zno

The novel PLGA/GE fibers encapsulated with DOX@mZnO were successfully fabricated, which enabled the delivery of two drugs with distinct rates.

scholarly journals Bioactivity-Guided Purification of Novel Herbal Antioxidant and Anti-NO Compounds from Euonymus laxiflorus Champ.

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 120 ◽  
Author(s):  
Van Nguyen ◽  
San-Lang Wang ◽  
Anh Nguyen ◽  
Zhi-Hu Lin ◽  
Chien Doan ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Natural Products ◽  
Biological Activities ◽  
The Novel ◽  
Health Food ◽  
Ic50 Values ◽  
Comparable Activity ◽  
New Compounds ◽  
First Time ◽  
Antidiabetic Effects

Euonymus laxiflorus Champ., a medicinal herb collected in Vietnam, has been reported to show several potent bioactivities, including anti-NO, enzyme inhibition, hypoglycemic and antidiabetic effects. Recently, the antioxidant activity of Euonymus laxiflorus Champ. trunk bark (ELCTB) has also been reported. However, the active antioxidant and anti-NO constituents existing in ELCTB have not been reported in the literature. The objective of this study was to purify the active antioxidants from ELCTB and investigate the anti-NO effect of the major constituents. Twenty-two phenolics isolated from ELCTB, including 12 compounds newly isolated in this study (1–12) and 10 constituents obtained from our previous work, were evaluated for their antioxidant activity. Of these, 12 compounds (4–6, 9, 13–15, 18–22) showed a potent antioxidant capacity (FRS50 = 7.8–58.11 µg/mL), in comparison to α-tocopherol (FRS50 = 23 µg/mL). In the anti-NO activity tests, Walterolactone A (1a) and B (1b) β-d-glucopyranoside (13) demonstrated the most effective and comparable activity to that of quercetin with max inhibition and IC50 values of 100%, 1.3 µg/mL, and 100%, 1.21 µg/mL, respectively. The crude extract and its major compounds showed no cytotoxicity on normal cells. Notably, three constituents (9, 11, and 12) were identified as new compounds, another three constituents, including 1, 7, and 8, were found to be new natural products, constituents 9 and 13 were determined to be new antioxidants, and compound 13 was reported to have novel potent anti-NO activity for the first time. The results of this study contribute to the enrichment of new natural products and compounds, as well as the novel biological activity of constituents isolated from Euonymus laxiflorus Champ. The current study also indicates ELCTB as a rich natural source of active phenolics. It is suggested that ELCTB could be developed as a health food with promising antioxidant and anti-NO effects, as well as other beneficial biological activities.

Autophagy as a Potential Therapeutic Target in Breast Cancer Treatment

2018 ◽  
Vol 18 (7) ◽  
pp. 629-639 ◽  
Author(s):  
Natalia Lisiak ◽  
Ewa Toton ◽  
Maria Rybczynska
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Hormone Receptors ◽  
Molecular Subtypes ◽  
Treatment Strategies ◽  
Breast Cancer Treatment ◽  
Therapy Failure ◽  
Potential Therapeutic Target ◽  
Apoptotic Pathway ◽  
Transduction Mechanisms

One of the crucial reasons of breast cancer therapy failure is an impairment of mechanisms responsible for metabolism and cellular homeostasis, which makes it difficult to foresee the response to the treatment. Targeted therapy in breast cancer is dictated by the expression of specific molecules such as growth factor or hormone receptors. Many types of breast cancer exhibit different abnormalities in the apoptotic pathway, which confer the resistance to many forms of chemotherapy. Because of the fundamental importance of autophagy in the development and progression of cancer and its ability to affect treatment response, there has been an immense research on molecular regulation and signal transduction mechanisms that control this process. Here, we summarize the present knowledge concerning different breast cancer treatment strategies using drugs approved for the treatment of different breast cancer molecular subtypes with targeting pathways and factors associated with autophagy modulation/ regulation.

AKT Kinase Addiction in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3431-3431
Author(s):  
Carolyne Bardeleben ◽  
Huajun Yan ◽  
Patrick Frost ◽  
Bao Hoang ◽  
Yijiang Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Line ◽  
Down Regulation ◽  
Akt Kinase ◽  
Apoptotic Pathway ◽  
Kinase Activation ◽  
Pi3k Inhibitors ◽  
Survival Pathway ◽  
U266 Cell ◽  
Induced Apoptosis

Abstract Cancer cells with activating kinase mutations are singularly hypersensitive to drugs that target these kinases, a phenomenon referred to as kinase or oncogene addiction. Although the AKT kinase is not known to be mutated in multiple myeloma (MM), it is frequently hyperactivated due to mutations in upstream signaling proteins. Previous work indicated that MM cells with heightened AKT activity were hypersensitive to drugs targeted to mTOR, a downstream substrate of AKT, suggesting an addiction to this pathway. “Kinase addiction” would theortically render the cell dependent on the kinase for growth. This dependency implies that other cascades of viability and/or proliferation may become downregulated subsequent to kinase activation. To test for AKT kinase addiction in MM we stably transfected the U266 MM cell line that is known to be protected against apoptosis by an autocrine Il-6/IL6R pathway (Caitlett-Falcone et al., Immunity 10, 105–115, 1999) with a constitutively active AKT construct (U266-AKT). AKT-transfected MM cells were protected against fas-induced apoptosis even when the autocrine IL-6 protective pathway was paralyzed by anti-IL6 and anti-IL6 receptor antibodies. However, as expected for an AKT addicted cell line, the U266-AKT cell line was more sensitive to agents that target the PI3/AKT/mTOR pathway, including two AKT inhibitors and the PI3K inhibitors LY294002 and wortmanin in terms of increased level of apoptosis and/or growth inhibition in comparison to the control U266 cell line. This “kinase-addicted” state was associated with down regulation of several components of the autocrine anti-apoptotic pathway of U266 cells. Expression of IL6, the IL6 receptor subunits gp80 and gp130 and STAT3 were all markedly silenced following AKT transfection. This down regulation of the survival pathway was relatively specific as expression of the fas receptor and VEGF receptors were relatively unaffected. The decrease in protein expression was also reflected in the decrease of mRNA for the receptor subunits, suggesting a transcriptional mechanism for down regulation. As expected from the decrease in autocrine IL-6 signaling, AKT-transfected cells also demonstrated a marked inhibition of Jak1 and MAPK 42/44 phosphorylation and enzymatic activity. In summary, over expression of activated AKT results in an AKT-addicted state whereby the MM cell becomes dependent on AKT for survival as other growth-promoting and anti-apoptotic cascades become paralyzed. These data support AKT as an important target for therapeutic intervention of MM and suggest such therapy would be most successful in patients whose MM cells contain the highest amount of activated AKT.

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