Light-Induced Caspase-3-Responsive Chimeric Peptide for Effective PDT/Chemo Combination Therapy with Good Compatibility

2020 ◽  
Vol 3 (4) ◽  
pp. 2392-2400
Author(s):  
Yong-Li Mu ◽  
Jin Zhang ◽  
Meng-Qing Xu ◽  
Mohamed F. Foda ◽  
Yang Wu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Caspase 3 ◽  
Chimeric Peptide

scholarly journals Cordycepin enhances the chemosensitivity of esophageal cancer cells to cisplatin by inducing the activation of AMPK and suppressing the AKT signaling pathway

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Ying Gao ◽  
Dan-Lei Chen ◽  
Mi Zhou ◽  
Zhou-san Zheng ◽  
Mei-Fang He ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Expression Levels ◽  
In Vivo Animal Model ◽  
Esophageal Cancer Cells

Abstract Although cisplatin (cDDP), is a first-line chemotherapy drug for esophageal cancer, it still has the potential to develop drug resistance and side effects. There is increasing evidence that cordycepin can work synergistically with other chemotherapy drugs. Therefore, we investigated whether combination therapy of cordycepin and cDDP may enhance the therapeutic effect of cDDP. We performed a series of functional tests to study the effect of medical treatment on esophageal cancer cells. We then used GO analysis to examine the pathways affected by treatment with cordycepin and cDDP. Next, we observed changes in the abundance of the selected pathway proteins. The in vivo animal model supported the results of the in vitro experiments. Co-treatment with cordycepin and cDDP inhibited cell growth, migration, and metastasis, as well as induced apoptosis. Cordycepin was found to effectively enhance activation of AMPK and inhibited activity of AKT. In all treatment groups, the expression levels of p-PI3K, p-Akt, p-p70S6K, Caspase-3, and Bcl-2 were significantly reduced, while the expression levels of p-AMPK, cleaved Caspase-3, and Bax increased, and the total levels of Akt, PI3K, and p70S6K levels remained unchanged. Overall, cordycepin was found to enhance the chemical sensitivity of esophageal cancer cells to cisplatin by inducing AMPK activation and inhibiting the AKT signaling pathway. Combination therapy of cordycepin and cisplatin represent a novel potential treatment of esophageal cancer.

scholarly journals Combination Therapy with a JNK Inhibitor and Hepatocyte Growth Factor for Restoration of Erectile Function in a Rat Model of Cavernosal Nerve Injury: Comparison with a JNK Inhibitor Alone or Hepatocyte Growth Factor Alone

2021 ◽  
Vol 22 (23) ◽  
pp. 12698
Author(s):  
Junghoon Lee ◽  
Soo Woong Kim ◽  
Min Chul Cho
Keyword(s):  
Growth Factor ◽  
Combination Therapy ◽  
Hepatocyte Growth Factor ◽  
Rat Model ◽  
Erectile Function ◽  
Caspase 3 ◽  
Combined Treatment ◽  
Group I ◽  
Jnk Inhibitors ◽  
Hepatocyte Growth

We determined if combined administration of JNK-inhibitors and HGF (hepatocyte-growth-factor) would restore erectile-function through both antiapoptotic and regenerative effects in a rat model of cavernous-nerve-crush-injury (CNCI), and compared the results with administration of JNK-inhibitor alone or HGF alone. We randomized 70 rats into 5 groups: sham-surgery-group (S), CNCI (I) group, a group treated with once-daily intraperitoneal-administration of 10.0-mg/kg of JNK-inhibitors (J), a twice-weekly intracavernosal-administration of 4.2-μg HGF group (H), and a combined-treatment with 10.0-mg/kg JNK-inhibitors and 4.2-μg HGF group (J+H). We investigated erectile-responses to electrostimulation, histological-staining, caspase-3-activity-assay, and immunoblotting at two-weeks postoperatively. The three treatment groups showed improvements in erectile-responses (ICP/MAP and AUC/MAP ratios) compared to Group-I. The erectile-responses in Group-J+H were greater than those in Group-J or Group-H. The erectile-responses in Group-J+H were generally normalized. Caspase-3-activity and cJun-phosphorylation in Group-J and Group-J+H improved compared to Group-I, whereas caspase-3-activity in Group-H partially improved. Protein-expression of PECAM-1, eNOS-phosphorylation, and smooth-muscle content in Group-J+H were normalized, although those in Group-J or Group-H were partially restored. Combination therapy with JNK-inhibitors and HGF can generally normalize erectile-function through anti-apoptosis and preservation of endothelium or SM in rat CNCI model. The combined treatment appears to be superior to the respective agent alone in terms of therapeutic effects.

Combination therapy with biomodulating agents induces apoptosis and changes of p21cip/waf and pro-caspase 3 expression in hepatoma cells in vitro

2001 ◽  
Vol 120 (5) ◽  
pp. A665-A666
Author(s):  
M GANSLMAYER ◽  
C HEROLD ◽  
M OCKER ◽  
M HERMANN ◽  
A GEERTS ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Caspase 3 ◽  
Hepatoma Cells

scholarly journals Effect of Combination Therapy with Neuroprotective and Vasoprotective Agents on Cerebral Ischemia

2018 ◽  
Vol 45 (3) ◽  
pp. 325-331
Author(s):  
Jiping Yang ◽  
Bei Yang ◽  
Baoxin Xiu ◽  
Jinchong Qi ◽  
Huaijun Liu
Keyword(s):  
Growth Factor ◽  
Combination Therapy ◽  
Water Content ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Time Window ◽  
Infarct Volume ◽  
Neural Cell ◽  
Control Group ◽  
Solution Saline

AbstractBecause most tested drugs are active against only one of the damaging processes associated with stroke, other mechanisms may cause cellular death. Thus, a combination of protective agents targeting different pathophysiological mechanisms may obtain better effects than a single agent. The major objective of this study was to investigate the effect of combination therapy with vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) after controlled ischemic brain injury in rabbits.Methods:Animals were randomly assigned to one of the following groups: sham group, saline-treated control group or NGF+VEGF-treated group. Animals received an intracerebral microinjection of VEGF and NGF or saline at 5 or 8 hours after ischemia. The two specified time points of administration were greater than or equal to the existing therapeutic time window for monoterapy with VEGF or NGF alone (3 or 5 hours of ischemia). Infarct volume, water content, neurological deficits, neural cell apoptosis and the expression of caspase-3 and Bcl-2 were measured.Results:Compared with saline-treated controls, the combination therapy of VEGF and NGF significantly reduced infarct volume, water content, neural cell apoptosis and the expression of caspase-3, up-regulated the expression of Bcl-2 and improved functional recovery (bothp<0.01) when administered 5 or 8 hours after ischemia. The earlier the administration the better the neuroprotection.Conclusions:These results showed that the combination therapy with VEGF and NGF provided neuroprotective effects. In addition, the time window of combination treatment should be at least 8 hours after ischemia, which was wider than monotherapy.RÉSUMÉ:Les effets d’une polythérapie combinant agents neuro-protecteurs et agents vasoprotecteurs dans les cas d’ischémie cérébrale.Contexte:Étant donné que la plupart des médicaments préalablement testés tendent à n’agir contre seulement un des processus de dommage associés aux AVC, il est possible que d’autres processus entraînent une mort cellulaire. À cet effet, il se pourrait qu’une combinaison d’agents protecteurs ciblant divers mécanismes physiopathologiques permette d’obtenir de meilleurs résultats qu’un simple agent. Après avoir suscité de façon contrôlée des lésions cérébrales ischémiques chez des lapins, l’objectif principal de la présente étude a donc été de se pencher sur l’impact d’une polythérapie combinant la protéine dite « facteur de croissance de l’endothélium vasculaire » (ou « VEGF » en anglais) avec le « facteur de croissance des nerfs » (ou « NGF » en anglais).Méthodes:Les animaux ont été attribués au hasard à l’un des groupes suivants : ceux ayant reçu un traitement fictif ; ceux, du groupe témoin, ayant bénéficié d’un traitement à base de solution saline ; et finalement ceux ayant été traités au moyen des VEGF et NGF. À noter que les lapins ont reçu une micro-injection intracérébrale de VEGF et de NGF ou de solution saline 5 heures ou 8 heures à la suite de leur AVC. Ces deux délais d’administration des VEGF et NGF sont équivalents ou supérieurs aux délais actuels d’administration des VEGF ou NGF à titre de monothérapie (3 heures ou 5 heures à la suite d’un AVC). Tant le volume des infarctus, le contenu en eau, les déficits neurologiques ainsi causés, l’apoptose des neurones que l’expression des protéases caspase 3 et des protéines Bcl-2 ont été mesurés.Résultats:Si on la compare au traitement à base de solution saline administré au groupe témoin, la polythérapie à base de VEGF et de NGF, lorsqu’administrée 5 heures ou 8 heures à la suite de l’AVC, a su réduire de façon notable le volume des infarctus, le contenu en eau, l’apoptose des neurones et l’expression des protéases caspase 3. Elle a également permis de réguler à la hausse l’expression des protéines Bcl-2 en plus d’entraîner une amélioration de la récupération fonctionnelle (p< 0,01 pour ces deux aspects). Ainsi donc, plus tôt l’on opte pour cette polythérapie, meilleure sera la neuroprotection encourue.Conclusions:Ces résultats démontrent que la polythérapie à base de VEGF et de NGF procure des effets neuroprotecteurs. Quant au délai d’administration de ce traitement combinatoire, il devrait être d’au moins 8 heures à la suite d’un AVC, ce qui est plus élevé que la monothérapie.

Combination therapy with biomodulating agents induces apoptosis and changes of p21cip/waf and pro-caspase 3 expression in hepatoma cells in vitro

2001 ◽  
Vol 120 (5) ◽  
pp. A665-A666
Author(s):  
Marion Ganslmayer ◽  
Christoph Herold ◽  
Matthias Ocker ◽  
Martin Hermann ◽  
Albert Geerts ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Caspase 3 ◽  
Hepatoma Cells

scholarly journals Combination of arsenic trioxide epigallocatechin-3-gallate and Resveratrol synergistically suppresses the growth and invasion in Brain tumor cell lines

2020 ◽  
Author(s):  
Roshanak S. Sajjadi ◽  
Samaneh Ahmadi ◽  
Marziye Mantashloo ◽  
Sepideh Mehrpour Layeghi ◽  
Yazdan Asgari ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Brain Tumor ◽  
Combination Therapy ◽  
Tumor Cell ◽  
Arsenic Trioxide ◽  
Caspase 3 ◽  
Cellular Proliferation ◽  
Glioma Cells ◽  
Tumor Cell Lines ◽  
Brain Tumor Cell

AbstractThe glioblastoma multiform has some properties including rapid growth, invasion, treatment resistance, and recurrence. Therefore, new therapies need to be developed that can be approved for using in patients. The previous study showed Arsenic Trioxide inhibits aggressive behavior in glioblastoma cells. Also, (–)-epigallocatechin-3-gallate prevents cellular proliferation, and invasion in multiple glioma cells. Resveratrol decreases cellular proliferation, induces cell death, and impaired the invasiveness of glioma cells. Combination therapy to inhibit cancer cells may have important clinical implications. Therefore, to assess the combination therapy of 2μM Arsenic trioxide, 100μM EGCG, and 100μM Resveratrol, we examined the metabolic activity, colony formation, media pH, cell proliferation, Caspase 3 activity, and gene expression analysis of BCL2, Caspase 3, MMP2, MMP9, CA9, u-PA, u-PAR, and Cathepsin B genes in apoptosis and invasion by both quantitative PCR experiments and Western blot assay. Systems biology tools also were used to obtain, the related network, involved pathways, and identifying the key genes in our selected criteria. The results of the study confirmed that the combined therapy prevents cell proliferation and induces of apoptosis in the Brain tumor cell lines including: U87-MG, A-172, and 1321N1. Furthermore, over-expression of caspase-3 and down-regulation of BCL-2, MMP-2, and MMP-9 confirmed that combination therapy leads to induces apoptosis and decreases invasion. Nevertheless, the lowering of pharmacological doses and improving therapeutic efficacy through combination therapy may provide advantages to treat resistance cancer cells with lower side effects. Finally, the results might suggest new modality for Glioblastoma treatment.

scholarly journals Caspase Mediated Synergistic Effect ofBoswellia serrataExtract in Combination with Doxorubicin against Human Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Mohammad Ahmed Khan ◽  
Mhaveer Singh ◽  
Masood Shah Khan ◽  
Abul Kalam Najmi ◽  
Sayeed Ahmad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Cell Lines ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Hepatic Toxicity ◽  
Isobolographic Analysis ◽  
Ic50 Value ◽  
Hep3b Cells ◽  
Synergistic Behavior

The study investigated the growth-inhibiting and apoptosis mediating effects ofB. serrataextract as monotherapy and combination therapy with DOX against hepatocellular carcinoma cell lines. Boswellic acid rich fraction ofB. serrataextract was prepared. MTT assay on HepG2 and Hep3B cells was carried out usingB. serrataalone and in combination with DOX. Further, caspase-3 activity, TNF-αlevel, and IL-6 level were estimated. Isobolographic analysis was carried out to evaluate the effect of combination therapy. Additionally, protective effect ofB. serrataextract on DOX induced hepatic toxicity was also evaluated in Wistar rats.B. serrataextract inhibited growth of HepG2 (IC50 value of21.21±0.92 μg/mL) as well as HepG2 (IC50 value of18.65±0.71 μg/mL). DOX inhibited growth in HepG2 and Hep3B cells with an IC50 of1.06±0.04 μg/mL and1.92±0.09 μg/mL. Isobolographic analysis showed combination index (CI) of DOX andB. serrataextract of0.53±0.03to0.79±0.02suggesting synergistic behavior against the two cell lines.B. serrataextract also caused dose dependent increase in caspase-3 activity, TNF-αlevel, and IL-6 level which was higher (P<0.001) with DOX (1 μM) andB. serrataextract (20 μg/mL) combination.B. serrataextract also protected Wistar rats against DOX induced hepatic toxicity.

Treatment of chemoresistant ovarian cancer with sigma2/SMAC and cisplatin.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16508-e16508
Author(s):  
Ivy Wilkinson-Ryan ◽  
Dirk Spitzer ◽  
Robert Mach ◽  
Suwanna Vangveravong ◽  
Peter S Goedegebuure ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Platinum Resistance ◽  
Apoptotic Pathway ◽  
Major Barrier ◽  
Skov3 Cells

e16508 Background: Platinum resistance continues to be a major barrier to the successful treatment of ovarian cancer. Overexpression of the X-linked inhibitor of apoptosis proteins (XIAP) contribute to platinum resistance in ovarian cancer through inhibition of caspases and up regulation of Akt activity. Second mitochondrial-derived activators of caspases (SMAC) is an endogenous protein that binds to and reverses XIAP-mediated inhibition of caspases. In order to exploit the SMAC-mediated pro-apoptotic pathway pharmacologically, SMAC mimetics have been developed and shown to induce apoptosis in cancer cells in vitro and in vivo. Untargeted cytotoxic cancer drugs bind to both malignant and normal tissue leading to significant toxicity. We have shown previously that solid tumors upregulate the sigma-2 receptor. We have also shown that sigma-2 ligands are internalized into cancer cells and are therefore an appealing vehicle for tumor targeted therapy. The goal of this study is to test if a conjugate drug of sigma-2 ligand and a SMAC mimetic (sigma-2/SMAC) in combination with chemotherapy is capable of overcoming chemoresistance in ovarian cancer. Methods: SKOV3 and OVCAR3 ovarian cancer cell lines were treated with sigma2/SMAC (1-16μM) and/or cisplatin (.5-10μg/mL). Viability assays were used to detect cell death. Luminescence-based caspase assays were used to compare the activity of caspase-3, -7, and -9 between treatment groups to document involvement of the XIAP survival pathway. Results: We found that sigma2-SMAC is synergistic when used in combination with cisplatin. Compared to untreated cells, SKOV3 cells treated with sigma/2SMAC (4uM), cisplatin .5ug/mL, or combination therapy showed 52.6%, 117.7%, and 34.8% viability respectively (p<.05). Cisplatin and sigma2/SMAC remained synergistic at increasing doses. Similar results were observed in OVCAR3 cells. Caspase-3 and -7 increased in combination therapy 1.2-fold over Sigma/2SMAC alone (4uM) and 7-fold over cisplatin alone (.5ug/mL) in SKOV3 cells (p<.05). Conclusions: This study suggests that the sigma2/SMAC conjugate provides a targeted means for overcoming chemoresistance in ovarian cancer through inhibition of XIAP and activation of caspases.

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