scholarly journals Phytochemicals as a Complement to Cancer Chemotherapy: Pharmacological Modulation of the Autophagy-Apoptosis Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Md. Ataur Rahman ◽  
Md. Abdul Hannan ◽  
Raju Dash ◽  
MD. Hasanur Rahman ◽  
Rokibul Islam ◽  
...  
Keyword(s):  
Cancer Chemotherapy ◽  
Apoptotic Pathway ◽  
Apoptosis Pathway ◽  
Pharmacological Modulation ◽  
Anticancer Properties ◽  
Promising Strategy ◽  
Wide Range ◽  
Therapeutic Development ◽  
Anticancer Target ◽  
Cellular Pathways

Bioactive plant derived compounds are important for a wide range of therapeutic applications, and some display promising anticancer properties. Further evidence suggests that phytochemicals modulate autophagy and apoptosis, the two crucial cellular pathways involved in the underlying pathobiology of cancer development and regulation. Pharmacological targeting of autophagy and apoptosis signaling using phytochemicals therefore offers a promising strategy that is complementary to conventional cancer chemotherapy. In this review, we sought to highlight the molecular basis of the autophagic-apoptotic pathway to understand its implication in the pathobiology of cancer, and explore this fundamental cellular process as a druggable anticancer target. We also aimed to present recent advances and address the limitations faced in the therapeutic development of phytochemical-based anticancer drugs.

Evaluation of the anticancer properties of the predicted hBaxBH3-mimetic compound 2-hydroxy-3,5-dinitrobenzamide in a mammary carcinogenesis-induced rat model

RSC Advances ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 2854-2869 ◽  
Author(s):  
Dakshinamurthy Sivakumar ◽  
Krishna Mohan Surapaneni ◽  
Ponnachipudhur Chinnaswamy Prabu ◽  
Natarajan Hari ◽  
Ponnusamy Thiruvasagam ◽  
...  
Keyword(s):  
Cancer Chemotherapy ◽  
Rat Model ◽  
Mammary Carcinogenesis ◽  
Anticancer Properties ◽  
Promising Strategy ◽  
Binding Interfaces ◽  
Mimetic Compound

Designing small molecular prototypes having potential to disrupt binding interfaces of pro-apoptotic–anti-apoptotic/BH3-only proteins is a promising strategy in cancer chemotherapy.

Chinese Medicine Protein and Peptide in Gene and Cell Therapy

2019 ◽  
Vol 20 (3) ◽  
pp. 251-264 ◽  
Author(s):  
Yinlu Feng ◽  
Zifei Yin ◽  
Daniel Zhang ◽  
Arun Srivastava ◽  
Chen Ling
Keyword(s):  
Chinese Medicine ◽  
Cell Therapy ◽  
Future Research ◽  
The Past ◽  
Promising Strategy ◽  
Wide Range ◽  
New Directions ◽  
Gene And Cell Therapy ◽  
Proteins And Peptides

The success of gene and cell therapy in clinic during the past two decades as well as our expanding ability to manipulate these biomaterials are leading to new therapeutic options for a wide range of inherited and acquired diseases. Combining conventional therapies with this emerging field is a promising strategy to treat those previously-thought untreatable diseases. Traditional Chinese medicine (TCM) has evolved for thousands of years in China and still plays an important role in human health. As part of the active ingredients of TCM, proteins and peptides have attracted long-term enthusiasm of researchers. More recently, they have been utilized in gene and cell therapy, resulting in promising novel strategies to treat both cancer and non-cancer diseases. This manuscript presents a critical review on this field, accompanied with perspectives on the challenges and new directions for future research in this emerging frontier.

scholarly journals The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration

2020 ◽  
Author(s):  
Paymaan Jafar-nejad ◽  
Berit Powers ◽  
Armand Soriano ◽  
Hien Zhao ◽  
Daniel A Norris ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Muscular Atrophy ◽  
Neurological Diseases ◽  
Cell Types ◽  
Rnase H ◽  
Central Administration ◽  
Spinal Motor Neurons ◽  
New Class ◽  
Wide Range ◽  
Therapeutic Development

Abstract Antisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing efforts to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal and non-neuronal cells. Therefore, it is important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and target RNA reduction throughout the CNS in neurons, oligodendrocytes, astrocytes and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.

scholarly journals Some notes on a historical perspective of panic disorder

2006 ◽  
Vol 55 (2) ◽  
pp. 154-160 ◽  
Author(s):  
Antonio Egidio Nardi
Keyword(s):  
Panic Disorder ◽  
20Th Century ◽  
19Th Century ◽  
Greek Mythology ◽  
Laboratory Studies ◽  
Biochemical Tests ◽  
Wide Range ◽  
Therapeutic Development ◽  
History Of ◽  
The 19Th Century

This article aims to describe important points in the history of panic disorder concept, as well as to highlight the importance of its diagnosis for clinical and research developments. Panic disorder has been described in several literary reports and folklore. One of the oldest examples lies in Greek mythology - the god Pan, responsible for the term panic. The first half of the 19th century witnessed the culmination of medical approach. During the second half of the 19th century came the psychological approach of anxiety. The 20th century associated panic disorder to hereditary, organic and psychological factors, dividing anxiety into simple and phobic anxious states. Therapeutic development was also observed in psychopharmacological and psychotherapeutic fields. Official classifications began to include panic disorder as a category since the third edition of the American Classification Manual (1980). Some biological theories dealing with etiology were widely discussed during the last decades of the 20th century. They were based on laboratory studies of physiological, cognitive and biochemical tests, as the false suffocation alarm theory and the fear network. Such theories were important in creating new diagnostic paradigms to modern psychiatry. That suggests the need to consider a wide range of historical variables to understand how particular features for panic disorder diagnosis have been developed and how treatment has emerged.

scholarly journals Effect of Daidzein on the Proliferation of Lung Cancer Cells Involved in the Apoptotic Signaling Pathway

2020 ◽  
Author(s):  
Hui Liu ◽  
Xiaobo Wang ◽  
Ouyang Jin ◽  
Denggang Fu ◽  
You Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathway ◽  
Tp53 Gene ◽  
Cell Counting ◽  
Pcr Analysis ◽  
Human Embryonic Lung ◽  
Bioactive Substances ◽  
Apoptosis Pathway ◽  
Wide Range ◽  
Proliferation And Apoptosis

Abstract Background: Daidzein is one of the key bioactive substances of soybean isoflavones that has a wide range of health benefits includes antineoplastic. Epidemiological evidence suggests that soy glycogen is associated with the incidence and prognosis of lung cancer. we purposed to assess the effect and molecular mechanism of daidzein on lung cancer, and to maximize therapy outcome for individualized treatment. Methods: In this report, H1299 were cultured in a medium with 10 μM daidzein for 6 hours , we detected the expression level of apoptosis-related genes in H1299 by cDNA microarray analysis. The selected genes were further validated by using RT-PCR analysis and Western blot. Finally, We usedflow cytometry to detect cell cycle alterations, and apoptosis the proliferation and apoptosis in HELF and H1299 cells were detected by Cell counting kit-8 assays. Results: These results indicate that low concentrations of isoflavone crude extract and daidzein could significantly affect the proliferation of H1299 (Human lung adenocarcinoma) and HELF (Human embryonic lung fibroblast) cells. The results of microarray in our study suggest that apoptosis-related genes are up-regulated induced by daidzein in H1299 cells and verified by RT-qPCR, particularly TP53 and caspase9. Western blotting shows the effect of daidzein on P53 and caspase9 in HELF cells be more obvious than it in H1299 cells. While the expression of TP53 was suppressed by pifithrin-α (PFTα) in HELF and H1299 cells, the mRNA and protein expression of TP53 still increase induced by daidzein, also, the effect of apoptosis induced by daidzein is involved in the P53 apoptosis pathway through inhibition of TP53 gene expression by PFTα. Conclusions: In conclusion, daidzein affected proliferation and apoptosis in HELF and H1299 cells, and the mechanism of apoptosis involved in the P53 signaling pathway.

scholarly journals pH-Responsive Nanoparticles for Cancer Immunotherapy: A Brief Review

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1613
Author(s):  
Yunfeng Yan ◽  
Hangwei Ding
Keyword(s):  
Cancer Immunotherapy ◽  
Ph Responsive ◽  
Promising Strategy ◽  
Cancer Immunity ◽  
Tumor Tissues ◽  
Wide Range ◽  
Powerful Approach ◽  
Key Steps ◽  
Antigen Presenting ◽  
Spatiotemporal Control

Immunotherapy has recently become a promising strategy for the treatment of a wide range of cancers. However, the broad implementation of cancer immunotherapy suffers from inadequate efficacy and toxic side effects. Integrating pH-responsive nanoparticles into immunotherapy is a powerful approach to tackle these challenges because they are able to target the tumor tissues and organelles of antigen-presenting cells (APCs) which have a characteristic acidic microenvironment. The spatiotemporal control of immunotherapeutic drugs using pH-responsive nanoparticles endows cancer immunotherapy with enhanced antitumor immunity and reduced off-tumor immunity. In this review, we first discuss the cancer-immunity circle and how nanoparticles can modulate the key steps in this circle. Then, we highlight the recent advances in cancer immunotherapy with pH-responsive nanoparticles and discuss the perspective for this emerging area.

Multiple Signal Pathways Involved in Crocetin-Induced Apoptosis in KYSE-150 Cells

Pharmacology ◽  
2019 ◽  
Vol 103 (5-6) ◽  
pp. 263-272 ◽  
Author(s):  
Sheng Li ◽  
Yuhua Qu ◽  
Xiu-Yin Shen ◽  
Ting Ouyang ◽  
Wen-Bin Fu ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Squamous Carcinoma ◽  
Annexin V ◽  
Signal Pathways ◽  
Dependent Manner ◽  
Apoptosis Pathway ◽  
Anticancer Properties ◽  
Multiple Signal ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Background: Crocetin is a carotenoid extracted from the traditional Chinese medical herb saffron. Previous studies have demonstrated that crocetin possesses anticancer properties that are effective against various cancers. As an extension of our earlier study, the present study explored the underlying mechanisms in crocetin’s anticancer effect on KYSE-150 cells. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), Mitogen-activated protein kinases (MAPK), and p53/p21 signal pathways play an important role in carcinogenesis, progression, and metastasis of carcinoma cells. Thus, we investigated crocetin’s effects on the PI3K/AKT, MAPK, and p53/p21 pathways in esophageal squamous carcinoma cell line KYSE-150 cells. Methods: KYSE-150 cells were treated with various concentrations of crocetin. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltertrazolium bromide assay, Annexin V/PI stain as well as Rh123 stain were used to evaluate the cell viability, apoptosis, and MMP. Western blot was used to detect the expression of PI3K, AKT, ERK1/2, p38, c-Jun NH-terminal kinase (JNK), P53, P21, Bcl-2, Bax, and cleaved caspase-3, which were associated with cell proliferation and apoptosis. Results: Our results showed that crocetin significantly inhibited the proliferation of KYSE-150 cells in a dose- and time-dependent manner. Crocetin also markedly induced cell apoptosis. Furthermore, we have found that crocetin not only inhibited the activation of PI3K/AKT, extracellular signal–regulated kinase-1/2 (ERK1/2), and p38 but also upregulated the p53/p21 level. These regulations ultimately triggered the mitochondrial-mediated apoptosis pathway with an eventual disruption of MMP, increased levels of Bax and cleaved caspase-3, and decreased levels of Bcl-2. Conclusions: These findings suggested that crocetin interfered with multiple signal pathways in KYSE-150 cells. Therefore, this study suggested that crocetin could potentially be used as a therapeutic candidate for the treatment of esophageal cancer.

scholarly journals A212 CHROMOFUNGIN PROTECTS AGAINST DSS-INDUCED COLITIS BY REGULATING P-53 APOPTITIC PATHWAY

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 84-85
Author(s):  
A Diarra ◽  
N Eissa ◽  
J Ghia
Keyword(s):  
B Cell Lymphoma ◽  
Peritoneal Macrophages ◽  
Cell Penetrating Peptide ◽  
Peptide Motif ◽  
Apoptotic Pathway ◽  
Apoptosis Pathway ◽  
Cell Penetrating ◽  
Vehicle Treatment ◽  
A Cell

Abstract Background Development of ulcerative colitis is associated with epithelial apoptosis mediated by p53-apoptotic pathway through the activation B-cell lymphoma 2 (Bcl-2), Bcl-2 associated-X protein (BAX) and Bcl-2 antagonist/killer-1 (BAK1) proteins. Chromofungin (CHR), a chromogranin-A derived peptide expressing a cell penetrating peptide motif, decreased the severity of colitis via the suppression of mucosal and pro-inflammatory macrophages-related p53-dependent apoptosis. Aims We aimed to investigate a) whether the gene profile expression of apoptosis could be extended to other p53-associated genes; b) whether the gene expression of some of the p53-apoptosis marker could be confirmed by protein analysis; and c) whether due to the cell penetrating peptide motif, CHR could enter into peritoneal macrophages. Methods UC-related colitis was induced in C57BL/6 mice (7 weeks) by administering dextran sulfate sodium (DSS) (5%, 5 days). Preventive CHR (2.5 mg/kg/day) or vehicle treatment started 1-day before colitis induction and lasted for 5-days. Profiler™ PCR Array was performed to screen a panel of 84 genes representative of the p53 signal pathway in colitic whole mucosa distal colonic samples treated or not with CHR. Western blot analysis was performed to confirm individual protein changes. Naïve macrophages were plated overnight and nonadherent cells were removed the next day. Cells were incubated with rhodamined CHR (4 ul) for 5, 10, 20, 30 min before washing and fixing them, detection was made via confocal microscopy. Results In colitic conditions, an up regulation of 26 genes associated to the p53-dependent apoptosis pathway were detected including Apaf1, Bax, Bbc3, Bcl2, Cradd, Fadd, Cul9, Pmaip1, Tnfrsf10b. In vivo CHR treatment decreased significantly the colitis and was associated with a significant downregulation of 19 genes including the 9 aforementioned when compared with biopsies from colitic groups. Compared to untreated groups, colitic mice treated with CHR demonstrated a significant decrease of BAX and BAK protein and the apoptotic ER stress inducer marker, X-Binding Protein 1. A large number of peritoneal macrophages displayed rhodamine within the all intracellular compartment. The presence of the peptide inside the cell can be visible as early as 5 min and the signal gradually increases. Conclusions CHR decreases the inflammatory process via the suppression of a large number of p53-related apoptotic proteins. CHR quickly enters the macrophage but the exact mechanism of entrance needs to be further defined. Targeting functional analysis of CHR may lead in the future to novel therapeutics for UC. Funding Agencies CCCNSERC

scholarly journals Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2687 ◽  
Author(s):  
Meichen Liu ◽  
Xueyuan Bai ◽  
Shiting Yu ◽  
Wenxue Zhao ◽  
Juhui Qiao ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Related Factor ◽  
Ros Scavenging ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
Ginsenoside Re ◽  
Apoptosis Pathway

Accumulation of amyloid-β (Aβ), which results in the formation of senile plaques that cause oxidative damage and neuronal cell death, has been accepted as the major pathological mechanism of Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis represents the effective strategies in combating AD. Ginsenoside Re (Re) has pharmacological effects against Aβ-induced neurotoxicity. However, its molecular mechanism remains elusive. The present study evaluated the effect of Re against Aβ-induced cytotoxicity and apoptosis in SH-SY5Y cells, and investigated the underlying mechanism. We demonstrate that Re inhibits the Aβ-triggered mitochondrial apoptotic pathway, as indicated by maintenance of mitochondrial functional, elevated Bcl-2/Bax ratio, reduced cytochrome c release, and inactivation of caspase-3/9. Re attenuated Aβ-evoked reactive oxygen species (ROS) production, apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, and JNK activation. ROS-scavenging abrogated the ability of Re to alter ASK-1 activation. Simultaneously, inhibition of JNK abolished Re-induced Bax downregulation in Aβ-challenged SH-SY5Y cells. In addition, Re enhanced activation of the nuclear factor-E2-related factor 2 (Nrf2) in Aβ-induced SH-SY5Y cells. Knockdown of Nrf2 by small interfering RNA targeting Nrf2 abolished the protective effect of Re. Our findings indicate that Re could be a potential therapeutic approach for the treatment of AD.

scholarly journals Virus-Encoded MicroRNAs Facilitate Gammaherpesvirus Latency and Pathogenesis In Vivo

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Emily R. Feldman ◽  
Mehmet Kara ◽  
Carrie B. Coleman ◽  
Katrina R. Grau ◽  
Lauren M. Oko ◽  
...  
Keyword(s):  
B Cells ◽  
Memory B Cells ◽  
Mutant Virus ◽  
Murine Gammaherpesvirus ◽  
Wide Range ◽  
Cellular Pathways ◽  
Regulatory Rnas ◽  
Host Target

ABSTRACTGammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV, or HHV-8), and murine gammaherpesvirus 68 (MHV68, γHV68, or MuHV-4), are B cell-tropic pathogens that each encode at least 12 microRNAs (miRNAs). It is predicted that these regulatory RNAs facilitate infection by suppressing host target genes involved in a wide range of key cellular pathways. However, the precise contribution that gammaherpesvirus miRNAs make to viral life cycle and pathogenesisin vivois unknown. MHV68 infection of mice provides a highly useful system to dissect the function of specific viral elements in the context of both asymptomatic infection and disease. Here, we report (i) analysis ofin vitroandin vivoMHV68 miRNA expression, (ii) generation of an MHV68 miRNA mutant with reduced expression of all 14 pre-miRNA stem-loops, and (iii) comprehensive phenotypic characterization of the miRNA mutant virusin vivo. The profile of MHV68 miRNAs detected in infected cell lines varied with cell type and did not fully recapitulate the profile from cells latently infectedin vivo. The miRNA mutant virus, MHV68.Zt6, underwent normal lytic replicationin vitroandin vivo, demonstrating that the MHV68 miRNAs are dispensable for acute replication. During chronic infection, MHV68.Zt6 was attenuated for latency establishment, including a specific defect in memory B cells. Finally, MHV68.Zt6 displayed a striking attenuation in the development of lethal pneumonia in mice deficient in IFN-γ. These data indicate that the MHV68 miRNAs may facilitate virus-driven maturation of infected B cells and implicate the miRNAs as a critical determinant of gammaherpesvirus-associated disease.IMPORTANCEGammaherpesviruses such as EBV and KSHV are widespread pathogens that establish lifelong infections and are associated with the development of numerous types of diseases, including cancer. Gammaherpesviruses encode many small noncoding RNAs called microRNAs (miRNAs). It is predicted that gammaherpesvirus miRNAs facilitate infection and disease by suppressing host target transcripts involved in a wide range of key cellular pathways; however, the precise contribution that these regulatory RNAs make toin vivovirus infection and pathogenesis is unknown. Here, we generated a mutated form of murine gammaherpesvirus (MHV68) to dissect the function of gammaherpesvirus miRNAsin vivo. We demonstrate that the MHV68 miRNAs were dispensable for short-term virus replication but were important for establishment of lifelong infection in the key virus reservoir of memory B cells. Moreover, the MHV68 miRNAs were essential for the development of virus-associated pneumonia, implicating them as a critical component of gammaherpesvirus-associated disease.

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