scholarly journals Effects of Scrophularia Oxysepala Methanolic Extract on Early Stages of Dimethylhydrazine-Induced Colon Carcinoma in Rats: Apoptosis Pathway Approach

2021 ◽  
Author(s):  
Ali Namvaran ◽  
Mehdi Fazeli ◽  
Safar Farajnia ◽  
Gholamreza Hamidian ◽  
Hassan Rezazadeh
Keyword(s):  
Colorectal Cancer ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Methanolic Extract ◽  
Aberrant Crypt Foci ◽  
Cancer Model ◽  
Apoptosis Pathway ◽  
Treatment Groups ◽  
Induction Of Apoptosis ◽  
Pre Treatment

Purpose: Colorectal cancer is one of the most prevalent cancers, worlwide. The present study aimed to examine the effects of Scrophularia Oxysepala (SO) methanolic extract on 1,2-dimethylhydrazine (DMH) induced colon cancer model in the Wistar rats. Methods: The animals administered DMH (40 mg/kg/S.C.) biweekly for two weeks to induce aberrant crypt foci (ACF). Other groups of animals were given the SO extract (50, 100 and 200 mg/kg/orally once/day) either before or after the DMH treatments. In the end, all animals were killed and at necropsy, the colon samples examined. The ACF, Aberrant crypt (AC), crypt multiplicity (CM), caspase 3 protein and apoptosis measurement were performed. Results: The SO extract significantly (P<0.001) decreased the number of AC, ACF, and CM in all pre and post-treated groups and caused significant increases in Caspase 3 and apoptosis as compared to the DMH group. However, post-treated animals showed significantly more effective than pre-treatment groups. Methanolic extract of SO showed a chemopreventive potential, by effectively reducing the number of AC, ACF, and CM and increasing caspase 3 protein and apoptosis. Conclusion: One of the possible mechanisms might be involved in the induction of apoptosis through the caspase 3 mediated pathway.

scholarly journals Evaluation of Novel 3-Hydroxyflavone Analogues as HDAC Inhibitors against Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Subhankar Biswas ◽  
Neetinkumar D. Reddy ◽  
B. S. Jayashree ◽  
C. Mallikarjuna Rao
Keyword(s):  
Colorectal Cancer ◽  
Caspase 3 ◽  
Hdac Inhibitors ◽  
Annexin V ◽  
Aberrant Crypt Foci ◽  
Treatment Groups ◽  
Activation Assay ◽  
Induced Apoptosis ◽  
Hct116 Cells

Alteration of epigenetic enzymes is associated with the pathophysiology of colon cancer with an overexpression of histone deacetylase 8 (HDAC8) enzyme in this tissue. Numerous reports suggest that targeting HDAC8 is a viable strategy for developing new anticancer drugs. Flavonols provide a rich source of molecules that are effective against cancer; however, their clinical use is limited. The present study investigated the potential of quercetin and synthetic 3-hydroxyflavone analogues to inhibit HDAC8 enzyme and evaluated their anticancer property. Synthesis of the analogues was carried out, and cytotoxicity was determined using MTT assay. Nonspecific and specific HDAC enzyme inhibition assays were performed followed by the expression studies of target proteins. Induction of apoptosis was studied through annexin V and caspase 3/7 activation assay. Furthermore, the analogues were assessed against in vivo colorectal cancer. Among the synthesized analogues, QMJ-2 and QMJ-5 were cytotoxic against HCT116 cells with an IC50 value of 68 ± 2.3 and 27.4 ± 1.8 µM, respectively. They inhibited HDAC enzyme in HCT116 cells at an IC50 value of 181.7 ± 22.04 and 70.2 ± 4.3 µM, respectively, and inhibited human HDAC8 and 1 enzyme at an IC50 value of <50 µM with QMJ-5 having greater specificity towards HDAC8. A reduction in the expression of HDAC8 and an increase in acetyl H3K9 expression were observed with the synthesized analogues. Both QMJ-2 and QMJ-5 treatment induced apoptosis through the activation of caspase 3/7 evident from 55.70% and 83.55% apoptotic cells, respectively. In vivo studies revealed a significant decrease in colon weight to length ratio in QMJ-2 and QMJ-5 treatment groups compared to DMH control. Furthermore, a reduction in aberrant crypt foci formation was observed in the treatment groups. The present study demonstrated the potential of novel 3-hydroxyflavone analogues as HDAC8 inhibitors with anticancer property against colorectal cancer.

scholarly journals COPB2 gene silencing inhibits colorectal cancer cell proliferation and induces apoptosis via the JNK/c-Jun signaling pathway

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0240106
Author(s):  
Yan Wang ◽  
Guangmei Xie ◽  
Min Li ◽  
Juan Du ◽  
Min Wang
Keyword(s):  
Colorectal Cancer ◽  
Gene Silencing ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Cell Counting ◽  
Apoptosis Pathway ◽  
Proliferation And Apoptosis ◽  
Related Proteins ◽  
Hct116 Cells

Objectives Colorectal cancer (CRC) is one of the most common malignant human tumors. It is associated with high morbidity and mortality rates. In recent years, tumor gene therapy has emerged as a promising new approach for colorectal cancer therapy. Herein, we identify and analyze the role of COPB2 (coatomer protein complex, subunit beta 2) in proliferation and apoptosis of CRC cells. Methods To investigate the role of COPB2 in the proliferation and apoptosis of CRC cells, a shCOPB2 vector and a shCtrl vector were constructed for transfection into RKO and HCT116 cells. Cells proliferation was subsequently measured via cell counting kit-8 (CCK8) assay and Celigo cell counting assay. Apoptosis was measured via flow cytometry. The activity level of Caspase 3/7 was measured. Finally, the level of several JNK/c-Jun apoptosis pathway-related proteins were measured to characterize the mechanism of apoptosis. Results Our results showed that the proliferation rate was decreased and the apoptosis rate was increased in shCOPB2-treated RKO and HCT116 cells compared to those in controls. After the silencing of COPB2, JNK/c-Jun signal pathway activation was increased, the expression levels of apoptosis pathway-related proteins, such as Bad, p53 and Caspase 3, were also increased. Conclusion COPB2 gene silencing can inhibit RKO and HCT116 cells proliferation and induce apoptosis via the JNK/c-Jun signaling pathway.

scholarly journals An Appraisal of Pumpkin Seed Extract in 1, 2-Dimethylhydrazine Induced Colon Cancer in Wistar Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
K. Yogeswara Chari ◽  
Picheswara Rao Polu ◽  
Rekha R. Shenoy
Keyword(s):  
Colon Cancer ◽  
Side Effects ◽  
Wistar Rats ◽  
Weight Ratio ◽  
Seed Extract ◽  
Aberrant Crypt Foci ◽  
Pumpkin Seed ◽  
Treatment Groups ◽  
Significant Difference ◽  
All Treatment

Background. Cancer is one of the most important public health burdens in developed and developing countries. Colon cancer (CC) is the sixth most common cause of death in India and third most important cause in developed countries. For treating cancer, several synthetic agents are available but they cause side effects. Therefore, there is a need to investigate plant derived anticancer agents with lesser side effects. In this direction, we have made an attempt to unravel the potential of pumpkin seed extract for treating colon cancer. Objective. The objective of this study was to evaluate pumpkin seed extract as prophylactic and treatment for 1, 2-dimethylhydrazine (DMH) induced colon cancer in Wistar rats. Materials and Methods. Male Wistar rats were divided into seven groups, namely, control, DMH (disease control), 5-Flurouracil (standard), treatment groups (100mg/kg and 200 mg/kg), and pretreatment groups (100mg/kg and 200 mg/kg) with pumpkin seed extract. The animals were euthanised at the end of study and colons were examined. Results. A significant difference in the aberrant crypt foci (ACF) number in all treatment groups compared to control and DMH groups were noted. Pretreatment group at a dose of 200 mg/kg showed a significant decrease in the colon length/weight ratio. Pretreatment groups showed a significant change in the colonic glutathione (GSH) and superoxide dismutase (SOD) levels when compared to control and DMH control. The nitrite content was decreased in treatment group 200 mg/kg at 5.203±0.852 when compared to DMH control at 8.506±3.866. All treatment groups demonstrated decreased hyperplasia and ACF in histology. Conclusion. Pumpkin seed may prevent the risk of CC when consumed in dietary proportions.

scholarly journals Ivermectin has New Application in Inhibiting Colorectal Cancer Cell Growth

2021 ◽  
Vol 12 ◽  
Author(s):  
Shican Zhou ◽  
Hang Wu ◽  
Wenjuan Ning ◽  
Xiao Wu ◽  
Xiaoxiao Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Annexin V ◽  
Optical Microscope ◽  
Dependent Manner ◽  
Mechanism Analysis ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Colorectal cancer (CRC) is the third most common cancer worldwide and still lacks effective therapy. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. However, whether ivermectin affects CRC is still unclear. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. We used CCK-8 assay to determine the cell viability, used an optical microscope to measure cell morphology, used Annexin V-FITC/7-AAD kit to determine cell apoptosis, used Caspase 3/7 Activity Apoptosis Assay Kit to evaluate Caspase 3/7 activity, used Western blot to determine apoptosis-associated protein expression, and used flow cytometry and fluorescence microscope to determine the reactive oxygen species (ROS) levels and cell cycle. The results demonstrated that ivermectin dose-dependently inhibited colorectal cancer SW480 and SW1116 cell growth, followed by promoting cell apoptosis and increasing Caspase-3/7 activity. Besides, ivermectin upregulated the expression of proapoptotic proteins Bax and cleaved PARP and downregulated antiapoptotic protein Bcl-2. Mechanism analysis showed that ivermectin promoted both total and mitochondrial ROS production in a dose-dependent manner, which could be eliminated by administering N-acetyl-l-cysteine (NAC) in CRC cells. Following NAC treatment, the inhibition of cell growth induced by ivermectin was reversed. Finally, ivermectin at low doses (2.5 and 5 µM) induced CRC cell arrest. Overall, ivermectin suppressed cell proliferation by promoting ROS-mediated mitochondrial apoptosis pathway and inducing S phase arrest in CRC cells, suggesting that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers.

scholarly journals Jaceosidin Induces Apoptosis in U87 Glioblastoma Cells through G2/M Phase Arrest

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Muhammad Khan ◽  
Bo Yu ◽  
Azhar Rasul ◽  
Ali Al Shawi ◽  
Fei Yi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Caspase 3 ◽  
Ethanol Extract ◽  
Inhibitory Effect ◽  
Bioactive Constituents ◽  
Growth Inhibitory Effect ◽  
Apoptosis Pathway ◽  
Growth Inhibitory ◽  
M Phase ◽  
Induction Of Apoptosis

Artemisia argyiis a widely used medicinal plant in China. The present study was designed to identify the bioactive constituents with antiglioma activity from leaves ofArtemesia argyi. A bioactivity guided approach based on MTT assay for cells growth inhibition led to the isolation of a flavonoid, “jaceosidin” from ethanol extract of leaves ofArtemesia argyi. The growth inhibitory effect of jaceosidin was explored using flow cytometry and Western blot studies. Our results showed that jaceosidin exerts growth inhibitory effect by arresting the cells at G2/M phase and induction of apoptosis. Furthermore, our study revealed that induction of apoptosis was associated with cell cycle arrest at G2/M phase, upregulation of p53 and Bax, decrease in mitochondrial membrane potential, release of cytochrome c, and activation of caspase 3. This mitochondrial-caspase-3-dependent apoptosis pathway was confirmed by pretreatment with caspase 3 inhibitor, Ac-DEVD-CHO. Our findings suggested that jaceosidin induces mitochondrial-caspase-3-dependent apoptosis in U87 cells by arresting the cell cycle at G2/M phase.

scholarly journals Hepatoprotective Potential ofSargassum muticumagainst STZ-Induced Diabetic Liver Damage in Wistar Rats by Inhibiting Cytokines and the Apoptosis Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Mohammed M. Safhi ◽  
Mohammad Firoz Alam ◽  
Sivagurunathan Moni Sivakumar ◽  
Tarique Anwer
Keyword(s):  
Glucose Level ◽  
Hepatic Injury ◽  
Caspase 3 ◽  
Methanolic Extract ◽  
Caspase 9 ◽  
Serum Enzyme ◽  
Cytokine Network ◽  
Apoptosis Pathway ◽  
Group 2 ◽  
Enzyme Markers

Liver inflammation and necrosis are the foremost problems interlinked with diabetes mellitus (DM). The methanolic extract ofSargassum muticum(MESM) plays a hepatoprotective role in streptozotocin- (STZ-) induced hepatic injury. In this study, STZ exposure induced diabetes that augmented hepatic damage, which was reflected in serum enzyme markers, the cytokine network, and caspase-3 and caspase-9 levels in Group 2. Exposure to the MESM tremendously modulated the levels of hepatic enzyme markers ALP, ACP, ALT, and AST in Groups 3 and 4. The cytokine network was well regulated by suppressing the release of cytokines, and the levels of caspase-3 and caspase-9 were also reduced in Groups 3 and 4. The present study suggests that MESM treatment at 200 and 500 mg protected the liver and also minimizes the glucose level. Thus, the MESM plays a key role in rejuvenating the liver and can modulate diabetes’s pathogenic effect by reducing the glucose level.

Changes of IL-4 and IFN-g expression in monocytes and T-helper lymphocytes while modeling of systemic juvenile idiopathic arthritis in Wistar rats

2018 ◽  
pp. 61-69
Author(s):  
В.Н. Сахаров ◽  
П.Ф. Литвицкий ◽  
Е.И. Алексеева ◽  
Н.А. Маянский ◽  
Р.Ш. Закиров
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Peripheral Blood Mononuclear Cells ◽  
Wistar Rats ◽  
Mononuclear Cells ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Treatment Groups ◽  
Blood Mononuclear Cells ◽  
T Helpers

Цель исследования - изучение перепрограммирования мононуклеарных лейкоцитов на модели системного ювенильного идиопатического артрита (сЮИА), воспроизводимой у крыс Wistar с использованием полного адъюванта Фрейнда и липополисахарида. Методика. сЮИА воспроизведен у 6-месячных крыс-самцов Wistar. На 40-е сут. эксперимента животные были разделены на 3 группы: 1-я группа - контроль; 2-я - группа доксициклина; 3-я - группа дексаметазона. Взятие проб крови у животных проводили на нулевые, 41-е и 55-е сут. Мононуклеарные клетки периферической крови выделяли гравиметрически, после чего окрашивали их на маркеры и внутриклеточные цитокины. Дифференцировали моноциты (CD3-CD4+) и Т-хелперы (CD3+CD4+). Анализировали динамику внутриклеточной экспрессии интерлейкина IL-4 (рассматривали как маркер про-М2 фенотипа, так как в случае выделения из клетки ИЛ-4 служит стимулятором М2 поляризации макрофагов) и IFN-g (как маркер про-М1 фенотипа) по данным проточной цитофлуориметрии. Применяли непараметрический статистический тест Mann-Whitney-Wilcoxon в программе R для статистической обработки данных. Результаты и заключение. При моделировании сЮИА выявлено закономерное изменение фенотипа моноцитов. Применение же доксициклина и дексаметазона приводило к более ранней поляризации их по про-М2-пути в отношении моноцитов (на 41-е сут.) в сравнении с контролем. Про-М1 эффект (на 55-е сут., в сравнении с контролем) выявлен также в группах доксициклина и дексаметазона. У животных разных групп обнаружены характерные динамические изменения внутриклеточной экспрессии цитокинов. Важно, что различная направленность поляризации фенотипа при сЮИА и применении препаратов наблюдается не только у моноцитов, но и у Т-хелперов. The study objective was to evaluate targeted reprogramming of peripheral blood mononuclear cells in systemic juvenile idiopathic arthritis (sJIA) modeled in 6-month-old male Wistar rats by co-administration of complete Freund’s adjuvant and lipopolysaccharide. Methods. On day 40 of the experiment, rats were divided into three groups: control, doxycycline, and dexamethasone groups. Blood samples were collected on days 0, 41, and 55. Peripheral blood mononuclear cells were isolated gravimetrically and stained for markers and cytokines. Monocytes (CD3-CD4+) and T-helpers (CD3+CD4+) were differentiated as target cells. IL-4 was considered a marker for the pro-M2 phenotype since IL-4 can activate M2 macrophage polarization; IFN-g was considered a marker for the pro-M1 phenotype. Time-related changes in the intracellular expression of IL-4 and IFN-g were studied using flow cytometry. Data were analyzed using nonparametric statistical tests (Mann-Whitney-Wilcoxon) in the R environment for statistical computing. Results and conclusions. Monocytes (like macrophages) underwent reprogramming during the development of modeled sJIA disease. In monocytes of doxycycline and dexamethasone treatment groups, pro-M2 effects were observed earlier (day 41) than in the control group. Pro-M1 effects were observed in monocytes of doxycycline and dexamethasone groups on day 55, as compared with the control group. Characteristic time-related changes of intracellular cytokine expression were described for different groups. Importantly, the differently directed phenotype polarization was observed in sJIA and treatment groups for both monocytes and T-helpers.

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