scholarly journals H2O2 Enhances the Anticancer Activity of TMPyP4 by ROS-mediated Mitochondrial Dysfunction and DNA Damage

2021 ◽  
Author(s):  
Jianqiang Chen ◽  
Xiangxiang Jin ◽  
Zhe Shen ◽  
Yanan Mei ◽  
Jufang Zhu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Anticancer Activity ◽  
Combined Treatment ◽  
Drug Action ◽  
Chemotherapeutic Drug ◽  
Normal Tissues ◽  
Telomerase Inhibitor ◽  
Apoptotic Protein ◽  
Cancer Tissues

Abstract Cancer is one of the diseases that threatens human health and is a leading cause of mortality worldwide. High levels of reactive oxygen species (ROS) have been observed in cancer tissues compared with normal tissues in vivo, and it is not yet known how this influences chemotherapeutic drug action. Cationic porphyrin 5,10,15,20-tetra-(N-methyl-4-pyridyl) porphyrin (TMPyP4) is a photosensitizer used in photodynamic therapy (PDT) and a telomerase inhibitor used in the treatment of telomerase-positive cancer. Here, we investigated the anticancer activity of TMPyP4 in A549 and PANC cells cultured in H2O2. The results showed that compared to TMPyP4 alone, the combination of TMPyP4 and H2O2 exhibited sensitization effects on cell viability and colony formation inhibition and apoptosis in A549 and PANC cells but had no effect in human normal MIHA cells. Mechanistically, the combination of TMPyP4 and H2O2 activates high ROS and mitochondrial membrane potential in A549 and PANC cells, resulting in intense DNA damage and DNA damage responses. Consequently, compared to TMPyP4 alone, TMPyP4 and H2O2 combined treatment upregulates the expression of BAX, cleaved caspase 3, and p-JNK, and downregulates the expression of Bcl-2 in A549 and PANC cells. Taken together, these data suggested that H2O2 enhanced the anticancer activity of TMPyP4-mediated ROS-dependent DNA damage and related apoptotic protein regulation, revealing that the high ROS tumor microenvironment plays an important role in chemotherapeutic drug action.

scholarly journals LINC-PINT impedes DNA repair and enhances radiotherapeutic response by targeting DNA-PKcs in nasopharyngeal cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
You-hong Wang ◽  
Zhen Guo ◽  
Liang An ◽  
Yong Zhou ◽  
Heng Xu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nasopharyngeal Cancer ◽  
Noncoding Rnas ◽  
Dependent Protein Kinase ◽  
Damage Repair ◽  
Dependent Protein ◽  
Cancer Tissues

AbstractRadioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.

scholarly journals The Rational Design and Biological Mechanisms of Nanoradiosensitizers

Nanomaterials ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 504 ◽  
Author(s):  
Hainan Sun ◽  
Xiaoling Wang ◽  
Shumei Zhai
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Dna Damage ◽  
Rational Design ◽  
Design Strategies ◽  
Biological Mechanisms ◽  
Normal Tissues ◽  
Current State

Radiotherapy (RT) has been widely used for cancer treatment. However, the intrinsic drawbacks of RT, such as radiotoxicity in normal tissues and tumor radioresistance, promoted the development of radiosensitizers. To date, various kinds of nanoparticles have been found to act as radiosensitizers in cancer radiotherapy. This review focuses on the current state of nanoradiosensitizers, especially the related biological mechanisms, and the key design strategies for generating nanoradiosensitizers. The regulation of oxidative stress, DNA damage, the cell cycle, autophagy and apoptosis by nanoradiosensitizers in vitro and in vivo is highlighted, which may guide the rational design of therapeutics for tumor radiosensitization.

Expression and Modulation of Carbohydrate-Binding Protein Galectin-3 in Multiple Myeloma Cells by Combined Treatment with GCS-100 and Dexamethasone.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4447-4447 ◽  
Author(s):  
Dharminder Chauhan ◽  
Yan Chang ◽  
Deli He ◽  
Teru Hideshima ◽  
Klaus Podar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Combined Treatment ◽  
Inhibitory Effect ◽  
Endothelial Cell Migration ◽  
Carbohydrate Binding ◽  
Conserved Sequence ◽  
Apoptotic Protein ◽  
Anti Tumor Activity ◽  
Terminal Domains

Abstract Galectins belong to the family of mammalian lectins sharing an evolutionary conserved sequence in their carbohydrate recognition binding (CRD) domains and exhibit a characteristic affinity for beta-galactoside-sugars. Based on their structure and CRD, galectins have been categorized into three different categories: 1) Prototype (Gal-1, 2, 5, 7, 10, 11, 13, and 14), 2) Chimera type (Gal-3), and 3) Tandem repeat type (Gal-6, 8, 9, and 12). In particular, Galcetin-3 (Gal-3) is associated with growth, differentiation, adhesion, RNA processing, and apoptosis (Apoptosis, 2005, 10: 267–75). Previous studies show that Gal-3 is expressed on tumor cell surface and mediate the transformation and metastasis of tumor cells in vivo(Apoptosis, 2005, 10: 267–75). Here, we show that Gal-3 is differentially expressed in multiple myeloma (MM) cell lines and purified patient cells, as determined by both western blotting and polymerase chain reaction (PCR). Importantly, Gal-3 shares structural similarities with the anti-apoptotic protein Bcl-2: both proteins are rich in proline, glycine, and alanine amino acid residues in their NH-2-terminal domains and contain anti-death motif Asp-Trp-Gly-Arg (NWGR) in their C-terminal domains (Proc Natl Acad Sci USA, 1996, 93: 6737–42). Gal-3, like Bcl-2, is therefore a potential therapeutic target. In this context, modified citrus pectins (MCP) have been reported to bind and inhibit Gal-3-induced human umbilical endothelial cell migration and micro vessel tube formation (Am J Pathol.2000, 156:899–909) as well as block tumor growth and metastasis (J Natl Cancer Inst. 2002, 94:1854–62). GCS-100 is a MCP currently under clinical development. Here we show that GCS-100 binds to human recombinant Gal-3. In MM cells, GCS-100 triggers apoptosis and enhances anti-tumor activity of the conventional agent Dexamethasone. We examined whether GCS-100-, Dex- or GCS-100 + Dex-induced MM cell death modulates Gal-3 or Bcl-2 expression. Treatment of MM.1S cells with either GCS-100 or Dex alone does not alter Gal-3 or Bcl-2 expression. However, combined treatment of MM cells with sub-toxic concentrations of GCS-100 and Dex markedly attenuates Gal-3 expression, without any changes in Bcl-2 levels, suggesting that alterations in Gal-3 are specific. Previous studies showed that Gal-3 inhibits mitochondrial pro-apoptotic protein cytochrome-c (cyto-c), and our results show that GCS-100 + Dex triggers the release of cyto-c from mitochondria to cytosol. Together, these data suggest that the combination of GCS-100 + Dex overcomes the inhibitory effect of Gal-3 on cyto-c, thereby inducing apoptosis. Since Gal-3 is widely expressed in MM cells, its inhibition may augment the anti-tumor activity of therapeutic regimens.

scholarly journals Real-time cancer diagnosis of breast cancer using fluorescence lifetime endoscopy based on the pH

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jooran Lee ◽  
Byungyeon Kim ◽  
Byungjun Park ◽  
Youngjae Won ◽  
Sang-Yeob Kim ◽  
...  
Keyword(s):  
Real Time ◽  
Fluorescence Lifetime ◽  
Normal Tissues ◽  
Diagnosis Of Cancer ◽  
Novel Method ◽  
Hematoxylin And Eosin ◽  
Cancer Tissues ◽  
The Relationship

AbstractA biopsy is often performed for the diagnosis of cancer during a surgical operation. In addition, pathological biopsy is required to discriminate the margin between cancer tissues and normal tissues in surgical specimens. In this study, we presented a novel method for discriminating between tumor and normal tissues using fluorescence lifetime endoscopy (FLE). We demonstrated the relationship between the fluorescence lifetime and pH in fluorescein using the proposed fluorescence lifetime measurement system. We also showed that cancer could be diagnosed based on this relationship by assessing differences in pH based fluorescence lifetime between cancer and normal tissues using two different types of tumor such as breast tumors (MDA-MB-361) and skin tumors (A375), where cancer tissues have ranged in pH from 4.5 to 7.0 and normal tissues have ranged in pH from 7.0 to 7.4. To support this approach, we performed hematoxylin and eosin (H&E) staining test of normal and cancer tissues within a certain area. From these results, we showed the ability to diagnose a cancer using FLE technique, which were consistent with the diagnosis of a cancer with H&E staining test. In summary, the proposed pH-based FLE technique could provide a real time, in vivo, and in-situ clinical diagnostic method for the cancer surgical and could be presented as an alternative to biopsy procedures.

scholarly journals Over-Expression of Centromere Protein U Participates in the Malignant Neoplastic Progression of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaomeng Hao ◽  
Yufan Qiu ◽  
Lixia Cao ◽  
Xiaonan Yang ◽  
Dongdong Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Ductal Carcinoma ◽  
Neoplastic Progression ◽  
Targeting Therapy ◽  
Normal Tissues ◽  
Centromere Protein ◽  
Cancer Models ◽  
Cancer Tissues

The expression of Centromere Protein U (CENP-U) is closely related to tumor malignancy. Till now, the role of CENP-U in the malignant progression of breast cancer remains unclear. In this study, we found that CENP-U protein was highly expressed in the primary invasive breast cancer tissues compared to the paired adjacent histologically normal tissues and ductal carcinoma in situ (DCIS) tissues. After CENP-U was knocked down, the proliferation and colony-forming abilities of breast cancer cells were significantly suppressed, whereas the portion of apoptotic cells was increased. Meanwhile, the PI3K/AKT/NF-κB pathway was significantly inhibited. In vivo studies showed that, the inhibition of CENP-U repressed the tumor growth in orthotopic breast cancer models. Therefore, our study demonstrated that the CENP-U might act as an oncogene and promote breast cancer progression via activation of the PI3K/AKT/NF-κB pathway, which suggests a promising direction for targeting therapy in breast cancer.

scholarly journals Knockdown of lncRNA LINC01234 Suppresses The Tumorigenesis of Liver Cancer via Sponging miR-513a-5p

2020 ◽  
Author(s):  
Wen Xu ◽  
Kesang Li ◽  
Changfeng Song ◽  
Xiaotong Wang ◽  
Yueqi Li ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Bioinformatics Analysis ◽  
Tumor Model ◽  
Downstream Target ◽  
Normal Tissues ◽  
Liver Cancer Cells ◽  
Gene And Protein Expression ◽  
Cancer Tissues

Abstract Background: Liver cancer is a frequent malignancy with poor prognosis. It has been reported that many lncRNAs could regulate the progression of liver cancer. To identify potential therapeutic targets for liver cancer, we conducted bioinformatics analysis of lncRNAs in tumor tissues and adjacent normal tissues. Methods: The differential expression of lncRNAs between liver cancer tissues and adjacent normal tissues were examined by bioinformatics analysis. Cell proliferation was tested by CCK-8. Cell apoptosis in liver cancer was detected by flow cytometry. Gene and protein expression in liver cancer cells were measured by q-PCR and Western-blot, respectively. Xenograft tumor model was established to verify the function of LINC01234 on liver cancer in vivo.Results: LINC01234 was found to be notably upregulated in liver cancer tissues. In addition, knockdown of LINC01234 significantly inhibited the proliferation, invasion and induced the apoptosis of liver cancer cells. Meanwhile, miR-513a-5p was a downstream target of LINC01234 and USP4 was a direct target of miR-513a-5p. Moreover, downregulation of LINC01234 inhibited the tumorigenesis of liver cancer via inactivating TGF-β signaling.Conclusion: Downregulation of LINC01234 could inhibit the progression of liver cancer. Thus, LINC01234 may serve as a potential novel target for treatment of liver cancer.

scholarly journals Stabilization of ADAM9 by N-α-acetyltransferase 10 protein contributes to promoting progression of androgen-independent prostate cancer

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Yung-Wei Lin ◽  
Yu-Ching Wen ◽  
Chih-Ying Chu ◽  
Min-Che Tung ◽  
Yi-Chieh Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Cancer ◽  
Feedback Regulation ◽  
Metastatic Potential ◽  
Normal Tissues ◽  
Tumor Growth And Metastasis ◽  
Cancer Tissues ◽  
Androgen Independent

Abstract N-α-Acetyltransferase 10 protein (Naa10p) was reported to be an oncoprotein in androgen-dependent prostate cancer (PCa; ADPC) through binding and increasing transcriptional activity of the androgen receptor (AR). PCa usually progresses from an androgen-dependent to an androgen-independent stage, leading to an increase in the metastatic potential and an incurable malignancy. At present, the role of Naa10p in androgen-independent prostate cancer (AIPC) remains unclear. In this study, in silico and immunohistochemistry analyses showed that Naa10 transcripts or the Naa10p protein were more highly expressed in primary and metastatic PCa cancer tissues compared to adjacent normal tissues and non-metastatic cancer tissues, respectively. Knockdown and overexpression of Naa10p in AIPC cells (DU145 and PC-3M), respectively, led to decreased and increased cell clonogenic and invasive abilities in vitro as well as tumor growth and metastasis in AIPC xenografts. From the protease array screening, we identified a disintegrin and metalloprotease 9 (ADAM9) as a potential target of Naa10p, which was responsible for the Naa10p-induced invasion of AIPC cells. Naa10p can form a complex with ADAM9 to maintain ADAM9 protein stability and promote AIPC’s invasive ability which were independent of its acetyltransferase activity. In contrast to the Naa10p-ADAM9 axis, ADAM9 exerted positive feedback regulation on Naa10p to modulate progression of AIPC in vitro and in vivo. Taken together, for the first time, our results reveal a novel cross-talk between Naa10p and ADAM9 in regulating the progression of AIPC. Disruption of Naa10p–ADAM9 interactions may be a potential intervention for AIPC therapy.

scholarly journals The Anticancer Activity for the Bumetanide-Based Analogs via Targeting the Tumor-Associated Membrane-Bound Human Carbonic Anhydrase-IX Enzyme

2020 ◽  
Vol 13 (9) ◽  
pp. 252
Author(s):  
Azizah M. Malebari ◽  
Tarek S. Ibrahim ◽  
Ibrahim M. Salem ◽  
Ismail Salama ◽  
Ahdab N. Khayyat ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Anticancer Activity ◽  
Tumor Hypoxia ◽  
Docking Studies ◽  
Solid Cancer ◽  
Normal Tissues ◽  
Kidney Carcinoma ◽  
Membrane Bound ◽  
Human Carbonic Anhydrase

The membrane-bound human carbonic anhydrase (hCA) IX is widely recognized as a marker of tumor hypoxia and a prognostic factor within several human cancers. Being undetected in most normal tissues, hCA-IX implies the pharmacotherapeutic advent of reduced off-target adverse effects. We assessed the potential anticancer activity of bumetanide-based analogues to inhibit the hCA-IX enzymatic activity and cell proliferation of two solid cancer cell lines, namely kidney carcinoma (A-498) and bladder squamous cell carcinoma (SCaBER). Bumetanide analogues efficiently inhibit the target hCA-IX in low nanomolar activity (IC50 = 4.4–23.7 nM) and have an excellent selectivity profile (SI = 14.5–804) relative to the ubiquitous hCA-II isoform. Additionally, molecular docking studies provided insights into the compounds’ structure–activity relationship and preferential binding of small-sized as well as selective bulky ligands towards the hCA-IX pocket. In particular, 2,4-dihydro-1,2,4-triazole-3-thione derivative 9c displayed pronounced hCA-IX inhibitory activity and impressive antiproliferative activity on oncogenic A-498 kidney carcinoma cells and is being considered as a promising anticancer candidate. Future studies will aim to optimize this compound to fine-tune its anticancer activity as well as explore its potential through in-vivo preclinical studies.

THYROID PROTEINS AND HORMONE SYNTHESIS IN HUMAN THYROID CANCER

1974 ◽  
Vol 76 (3) ◽  
pp. 651-669 ◽  
Author(s):  
Colette Thomas-Morvan ◽  
Berthe Nataf ◽  
Maurice Tubiana
Keyword(s):  
Thyroid Cancer ◽  
Organ Culture ◽  
Human Thyroid ◽  
Coupling Reactions ◽  
Variable Effect ◽  
Hormone Synthesis ◽  
Normal Tissues ◽  
Cancer Tissues ◽  
Stable Iodine

ABSTRACT Thyroid iodoproteins and hormone synthesis have been studied in vivo and in organ culture in 44 cases of thyroid cancer. In a few cases, Tg1) (17–19 S) is virtually absent; a portion of the light fractions (3–8 S), which seems to represent some precursors of Tg, incorporated in culture the 14C-amino acids. In most of the cases, the solubility profiles, sedimentation patterns as well as electrophoretic migration of proteins were normal. The content of Tg and the concentration of stable iodine (127I) in Tg are less than that of "normal" tissues, and the deficiency in iodination appears to be more pronounced than the depression of the Tg synthesis. Most frequently the radioiodine uptake is very low and most of the iodine remains in the gland as iodide and MIT. In those tissues which organify radioiodine, it is incorporated into tyrosine molecules and is metabolized to the stage of iodothyronines (T4 + T3); there must then be little or no defect in coupling reactions. There is a linear relation between the concentration of stable iodine in Tg and the level of hormone synthesis, as we have found in "normal" gland and benign thyroid diseases. These results suggest that the overall disorder seen in thyroid cancer tissues appears to involve one of the initial steps of hormone synthesis. The very low mean iodination of Tg in these tissues suggests a great heterogeneity in the functional activity throughout the tumour. TSH has a very variable effect on thyroid cancer tissues maintained in organ culture: in 46 % of the cases the hormone has no effect. In some instances TSH may significantly increase the incorporation of radioiodine into soluble iodoproteins, Tg as well as the albumin fraction.

Sign in / Sign up

Export Citation Format

Share Document