Vitamin D as Radiosensitizer: A Review in Cell Line -

2020 ◽  
Vol 10 (6) ◽  
pp. 315-324
Author(s):  
Fahmi Radityamurti ◽  
Fauzan Herdian ◽  
Tiara Bunga Mayang Permata ◽  
Handoko Handoko ◽  
Henry Kodrat ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Differentiation ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agent ◽  
Medical Literature ◽  
In Vitro Studies ◽  
Anti Cancer

Introduction: Vitamin D has been shown to have anti-cancer properties such as antioxidants, anti-proliferative, and cell differentiation. The property of vitamin D as an anticancer agent triggers researchers to find out whether vitamin D is useful as a radiosensitizer. Multiple studies have been carried out on cell lines in various types of cancer, but the benefits of vitamin D as a radiosensitizer still controversial. This paperwork aims to investigate the utilization of Vitamin D3 (Calcitriol) as radiosensitizer in various cell line through literature review.Methods: A systematic search of available medical literature databases was performed on in-vitro studies with Vitamin D as a radiosensitizer in all types of cell lines. A total of 11 in-vitro studies were evaluated.Results: Nine studies in this review showed a significant effect of Vitamin D as a radiosensitizer agent by promoting cytotoxic autophagy, increasing apoptosis, inhibiting of cell survival and proliferation, promoting gene in ReIB inhibition, inducing senescene and necrosis. The two remaining studies showed no significant effect in the radiosensitizing mechanism of Vitamin D due to lack of evidence in-vitro settings.Conclusion: Vitamin D have anticancer property and can be used as a radiosensitizer by imploring various mechanism pathways in various cell lines. Further research especially in-vivo settings need to be evaluated.

scholarly journals Policing Cancer: Vitamin D Arrests the Cell Cycle

2020 ◽  
Vol 21 (23) ◽  
pp. 9296
Author(s):  
Sachin Bhoora ◽  
Rivak Punchoo
Keyword(s):  
Cell Cycle ◽  
Vitamin D ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
In Vitro Studies ◽  
Vitamin D Metabolites ◽  
Cell Cycle Regulators ◽  
Cycle Arrest ◽  
Anti Cancer

Vitamin D is a steroid hormone crucial for bone mineral metabolism. In addition, vitamin D has pleiotropic actions in the body, including anti-cancer actions. These anti-cancer properties observed within in vitro studies frequently report the reduction of cell proliferation by interruption of the cell cycle by the direct alteration of cell cycle regulators which induce cell cycle arrest. The most recurrent reported mode of cell cycle arrest by vitamin D is at the G1/G0 phase of the cell cycle. This arrest is mediated by p21 and p27 upregulation, which results in suppression of cyclin D and E activity which leads to G1/G0 arrest. In addition, vitamin D treatments within in vitro cell lines have observed a reduced C-MYC expression and increased retinoblastoma protein levels that also result in G1/G0 arrest. In contrast, G2/M arrest is reported rarely within in vitro studies, and the mechanisms of this arrest are poorly described. Although the relationship of epigenetics on vitamin D metabolism is acknowledged, studies exploring a direct relationship to cell cycle perturbation is limited. In this review, we examine in vitro evidence of vitamin D and vitamin D metabolites directly influencing cell cycle regulators and inducing cell cycle arrest in cancer cell lines.

Largazole, a Novel Cyclic Peptide Histone Deacetylase Inhibitor, Demonstrates Anti-MM Effects Alone and Increases the Anti-MM Effects of Bortezomib.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4925-4925
Author(s):  
Zhi-Wei Li ◽  
Mengyin Hu ◽  
Crystal Leung ◽  
Jeffrey A Steinberg ◽  
Jing Shen ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Cyclic Peptide ◽  
Hdac Inhibitors ◽  
In Vitro Studies ◽  
Normal Peripheral Blood ◽  
Anti Cancer

Abstract Abstract 4925 Multiple myeloma (MM) remains an incurable malignancy. Therefore, there is a need for the development of new agents to improve the survival for these patients. Histone acetylation, which is controlled by the balanced activities between histone acetyltransferase (HAT) and histone deacetylase (HDAC), is a major epigenetic modification that contributes to tumorigenesis. Through inhibition of HDAC activity, HDAC inhibitors (HDACis) increase acetylation levels of histones as well as other tumor suppressor gene products; and, therefore, are potential anti-cancer agents. Based on the structures, currently available HDAC inhibitors can be divided into four groups, including hydroxamates, cyclic peptides, aliphatic acids, and benzamides. Largazole is a novel member of the cyclic peptide family of HDACis some of which have shown anti-cancer effects in preclinical studies and early clinical trials including for patients with MM especially when used in combination with the proteasome inhibitor bortezomib. In this study, we have explored the potential anti-MM activity of largazole alone and in combination with bortezomib in preclinical in vitro studies. As demonstrated using the MTS assay, this HDACi inhibits the growth of cells from the MM cell lines RPMI8226, U266 and MM1S with an IC50 of approximately 0.2 μM in all three cell lines. In addition, largazole also induces apoptotic death of MM cells as determined with Annexin V staining followed by flow cytometric analysis. Largazole was also shown to induce histone acetylation in MM cells as determined with Western blot analysis using an antibody against acetyl-histone H4. Furthermore, the combination of this HDACi and bortezomib demonstrated synergistic anti-MM effects in these cell lines. Importantly, treatment of mice with largazole shows excellent tolerability at doses that produce concentrations in vivo that are higher than those shown to produce anti-MM effects in our in vitro studies. Thus, largazole may be a potential new agent for the treatment of MM alone and in combination with bortezomib. Currently, we are evaluating the cytotoxic effects of largazole on normal peripheral blood and bone marrow mononuclear cells in vitro and in vivo using our severe combined immunodeficiency mouse models of human myeloma alone as well as in combination with several other drugs including bortezomib used in the treatment of MM. Updated results from these ongoing studies will be presented at the meeting. Disclosures Berenson: Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

scholarly journals Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Farnaz Dabbagh Moghaddam ◽  
Iman Akbarzadeh ◽  
Ehsan Marzbankia ◽  
Mahsa Farid ◽  
Leila khaledi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cell Lines ◽  
Encapsulation Efficiency ◽  
Inbred Mice ◽  
Breast Cancer Treatment ◽  
Anticancer Effect ◽  
Anti Cancer

Abstract Background Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. Results This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Conclusions Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

scholarly journals Temozolomide sensitivity of malignant glioma cell lines – a systematic review assessing consistencies between in vitro studies

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Michael T. C. Poon ◽  
Morgan Bruce ◽  
Joanne E. Simpson ◽  
Cathal J. Hannan ◽  
Paul M. Brennan
Keyword(s):  
Cell Viability ◽  
Malignant Glioma ◽  
Cell Line ◽  
Cell Lines ◽  
Glioma Cell ◽  
Glioma Cell Line ◽  
In Vitro Studies ◽  
Experimental Conditions ◽  
Glioma Cell Lines

Abstract Background Malignant glioma cell line models are integral to pre-clinical testing of novel potential therapies. Accurate prediction of likely efficacy in the clinic requires that these models are reliable and consistent. We assessed this by examining the reporting of experimental conditions and sensitivity to temozolomide in glioma cells lines. Methods We searched Medline and Embase (Jan 1994-Jan 2021) for studies evaluating the effect of temozolomide monotherapy on cell viability of at least one malignant glioma cell line. Key data items included type of cell lines, temozolomide exposure duration in hours (hr), and cell viability measure (IC50). Results We included 212 studies from 2789 non-duplicate records that reported 248 distinct cell lines. The commonest cell line was U87 (60.4%). Only 10.4% studies used a patient-derived cell line. The proportion of studies not reporting each experimental condition ranged from 8.0–27.4%, including base medium (8.0%), serum supplementation (9.9%) and number of replicates (27.4%). In studies reporting IC50, the median value for U87 at 24 h, 48 h and 72 h was 123.9 μM (IQR 75.3–277.7 μM), 223.1 μM (IQR 92.0–590.1 μM) and 230.0 μM (IQR 34.1–650.0 μM), respectively. The median IC50 at 72 h for patient-derived cell lines was 220 μM (IQR 81.1–800.0 μM). Conclusion Temozolomide sensitivity reported in comparable studies was not consistent between or within malignant glioma cell lines. Drug discovery science performed on these models cannot reliably inform clinical translation. A consensus model of reporting can maximise reproducibility and consistency among in vitro studies.

scholarly journals Establishment of a novel human CIC-DUX4 sarcoma cell line, Kitra-SRS, with autocrine IGF-1R activation and metastatic potential to the lungs

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sho Nakai ◽  
Shutaro Yamada ◽  
Hidetatsu Outani ◽  
Takaaki Nakai ◽  
Naohiro Yasuda ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Fusion Gene ◽  
Primary Tumour ◽  
Chromosomal Rearrangements ◽  
Basic Research ◽  
Metastatic Potential ◽  
Original Tumour

Abstract Approximately 60–70% of EWSR1-negative small blue round cell sarcomas harbour a rearrangement of CIC, most commonly CIC-DUX4. CIC-DUX4 sarcoma (CDS) is an aggressive and often fatal high-grade sarcoma appearing predominantly in children and young adults. Although cell lines and their xenograft models are essential tools for basic research and development of antitumour drugs, few cell lines currently exist for CDS. We successfully established a novel human CDS cell line designated Kitra-SRS and developed orthotopic tumour xenografts in nude mice. The CIC-DUX4 fusion gene in Kitra-SRS cells was generated by t(12;19) complex chromosomal rearrangements with an insertion of a chromosome segment including a DUX4 pseudogene component. Kitra-SRS xenografts were histologically similar to the original tumour and exhibited metastatic potential to the lungs. Kitra-SRS cells displayed autocrine activation of the insulin-like growth factor 1 (IGF-1)/IGF-1 receptor (IGF-1R) pathway. Accordingly, treatment with the IGF-1R inhibitor, linsitinib, attenuated Kitra-SRS cell growth and IGF-1-induced activation of IGF-1R/AKT signalling both in vitro and in vivo. Furthermore, upon screening 1134 FDA-approved drugs, the responses of Kitra-SRS cells to anticancer drugs appeared to reflect those of the primary tumour. Our model will be a useful modality for investigating the molecular pathology and therapy of CDS.

scholarly journals Therapeutic Anticancer Uses of the Active Principles of “Rhopalurus junceus” Venom

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 382
Author(s):  
Mario Dioguardi ◽  
Giorgia Apollonia Caloro ◽  
Luigi Laino ◽  
Mario Alovisi ◽  
Diego Sovereto ◽  
...  
Keyword(s):  
Cell Lines ◽  
Carcinoma Cell ◽  
Meta Analysis ◽  
Scorpion Venom ◽  
In Vitro Studies ◽  
Active Components ◽  
Eligibility Criteria ◽  
Carcinoma Cell Lines ◽  
Anti Cancer

The Rhopalurus junceus is a scorpion belonging to the Buthidae family that finds its habitat in Cuba. This scorpion is known by the common name of “Blue Scorpion”. The venom is used on the island of Cuba as an alternative cure for cancer and, more recently, in the research of active components for biomedicine. Recently, the venom has been tested in several studies to investigate its effects on cancer cell lines, and the initial results of in vitro studies demonstrated how this poison can be effective on certain carcinoma cell lines (Hela, SiHa, Hep-2, NCI-H292, A549, MDA-MB-231, MDA-MB-468, and HT-29). The aim of this review is, therefore, to describe the effects of the venom on carcinoma lines and to investigate all anti-cancer properties studied in the literature. The research was conducted using four databases, Pub Med, Scopus, EBSCO, and Web of Science, through the use of keywords, by two independent reviewers following the PRISMA protocol, identifying 57 records. The results led to a total of 13 articles that met the eligibility criteria. The data extracted for the purpose of meta-analysis included the IC50 of the venom on carcinoma cell lines. The results of the meta-analysis provided a pooled mean of the IC50 of 0.645 mg/mL (95% CI: 0.557, 0.733), with a standard error (SE) = 0.045, p < 0.001. The analysis of the subgroups, differentiated by the type of cell line used, provided insight regarding how the scorpion venom was effective on the cell lines of lung origin (NCI-H292, A549, and MRC-5) with a pooled mean of IC50 0.460 mg/mL (95% CI: 0.290, 0.631) SE (0.087) p < 0.001. The results described in the literature for in vitro studies are encouraging, and further investigations should be carried out and deepened.

scholarly journals Establishment of B-Cell Lymphoma Cell Lines Persistently Infected with Hepatitis C Virus In Vivo and In Vitro: the Apoptotic Effects of Virus Infection

2003 ◽  
Vol 77 (3) ◽  
pp. 2134-2146 ◽  
Author(s):  
Vicky M.-H. Sung ◽  
Shigetaka Shimodaira ◽  
Alison L. Doughty ◽  
Gaston R. Picchio ◽  
Huong Can ◽  
...  
Keyword(s):  
Hepatitis C ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Culture System ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hcv Rna

ABSTRACT Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Studies of HCV replication and pathogenesis have so far been hampered by the lack of an efficient tissue culture system for propagating HCV in vitro. Although HCV is primarily a hepatotropic virus, an increasing body of evidence suggests that HCV also replicates in extrahepatic tissues in natural infection. In this study, we established a B-cell line (SB) from an HCV-infected non-Hodgkin's B-cell lymphoma. HCV RNA and proteins were detectable by RNase protection assay and immunoblotting. The cell line continuously produces infectious HCV virions in culture. The virus particles produced from the culture had a buoyant density of 1.13 to 1.15 g/ml in sucrose and could infect primary human hepatocytes, peripheral blood mononuclear cells (PBMCs), and an established B-cell line (Raji cells) in vitro. The virus from SB cells belongs to genotype 2b. Single-stranded conformational polymorphism and sequence analysis of the viral RNA quasispecies indicated that the virus present in SB cells most likely originated from the patient's spleen and had an HCV RNA quasispecies pattern distinct from that in the serum. The virus production from the infected primary hepatocytes showed cyclic variations. In addition, we have succeeded in establishing several Epstein-Barr virus-immortalized B-cell lines from PBMCs of HCV-positive patients. Two of these cell lines are positive for HCV RNA as detected by reverse transcriptase PCR and for the nonstructural protein NS3 by immunofluorescence staining. These observations unequivocally establish that HCV infects B cells in vivo and in vitro. HCV-infected cell lines show significantly enhanced apoptosis. These B-cell lines provide a reproducible cell culture system for studying the complete replication cycle and biology of HCV infections.

Glutathione S-transferases in tracheobronchial epithelium

1995 ◽  
Vol 269 (4) ◽  
pp. L473-L481
Author(s):  
P. M. Reddy ◽  
C. P. Tu ◽  
R. Wu
Keyword(s):  
Cell Differentiation ◽  
Environmental Factors ◽  
Enzymatic Activity ◽  
Cell Lines ◽  
Mucous Cell ◽  
Collagen Gel ◽  
Bronchial Epithelium ◽  
High Level

The purpose of this study is to characterize glutathione S-transferase (GST) gene expression in airway epithelium both in vivo and in vitro. Immunohistochemical staining of nonhuman primate lungs of well-controlled healthy animals reveals the presence of alpha- and pi-class GST isoenzymes in ciliated bronchial epithelium. The stain of mu-GST antibody is either very low or absent in some of these monkey lungs. We observed that primary tracheobronchial epithelial (TBE) cells isolated from human and monkey pulmonary tissues maintain a relatively high level of GST enzymatic activity in culture, compared with various immortalized human TBE cell lines and other nonpulmonary cell lines. Northern blot analysis demonstrated the presence of mu-, pi-, and microsomal-GST messages but not the alpha-class message in cultures of primary TBE cells as well as in various human TBE cell lines. The expression of mu- and pi-class GST genes can be further regulated in culture by various environmental factors; however, most of these regulating factors are associated with TBE cell differentiation in culture. For instance, vitamin A treatment, which was shown to enhance mucous cell differentiation in vitro, stimulated the message levels of mu- and pi-class GST. Furthermore, plating cells on collagen gel substrata, which also enhanced mucous cell differentiation in culture, instead of plastic culture surface, enhanced total GST enzymatic activity by eightfold, and this enhancement is related to an increase in the expression of the pi-class GST gene. These results demonstrated that GST genes are differentially expressed and regulated by various environmental factors in primary TBE cells and various cell lines, and the regulation is correlated to the mucous cell differentiation in culture.

scholarly journals Overexpression of cyclin D1 in the Dami megakaryocytic cell line causes growth arrest

Blood ◽  
1995 ◽  
Vol 86 (1) ◽  
pp. 294-304 ◽  
Author(s):  
CC Wilhide ◽  
C Van Dang ◽  
J Dipersio ◽  
AA Kenedy ◽  
PF Bray
Keyword(s):  
Cyclin D1 ◽  
Cell Line ◽  
Cell Lines ◽  
Northern Blotting ◽  
Mrna Levels ◽  
Cyclin Dependent Kinases ◽  
Megakaryocyte Differentiation ◽  
Megakaryocytic Cell

The maturation of megakaryocytes in vivo requires polyploidization or repeated duplication of DNA without cytokinesis. As DNA replication and cytokinesis are tightly regulated in somatic cells by cyclins and cyclin-dependent kinases, we sought to determine the pattern of cyclin gene expression in cells that undergo megakaryocytic differentiation and polyploidization. The Dami megakaryocytic cell line differentiates and increases ploidy in response to phorbol 12-myristate 13-acetate (PMA) stimulation in vitro. We used Northern blotting to analyze mRNA levels of cyclins A, B, C, D1, and E in PMA-induced Dami cells and found that cyclin D1 mRNA levels increased dramatically (18-fold). Similar increases in cyclin D1 mRNA were obtained for other cell lines (HEL and K562) with megakaryocytic properties, but not in HeLa cells. The increase in cyclin D1 was confirmed by Western immunoblotting of PMA-treated Dami cells. This finding suggested that cyclin D1 might participate in megakaryocyte differentiation by promoting endomitosis and/or inhibiting cell division. To address these possibilities, we constructed two stable Zn+2-inducible, cyclin D1-overexpressing Dami cell lines. Cyclin D1 expression alone was not sufficient to induce polyploidy, but in conjunction with PMA-induced differentiation, polyploidization was slightly enhanced. However, unlike other cell systems, cyclin D1 overexpression caused cessation of cell growth. Although the mechanism by which cyclin D1 may affect megakaryocyte differentiation is not clear, these data demonstrate that cyclin D1 is upregulated in differentiating megakaryocytic cells and may contribute to differentiation by arresting cell proliferation.

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