Melanoma Cell Lines Role in Obtaining New Drug Candidates for Combating the Malignant Pathology of the Cutaneous Organ

As prophylactic and therapeutic approaches for melanoma, of great interest and importance are the in vitro studies using cell lines to elucidate several tumoral phenomena. Therefore, the similarities and differences between the different tumor cells must be known and understood in order to obtain a more accurate correlation with processes that occur in vivo. In this study, six cell lines of melanoma, both of mouse and human origin were analyzed from the point of view of cell culture growth, morphology and use in the research of new therapies. In brief, the current paper exhibits a comparison of melanoma cells which can be utilized as a starting point for further in vitro studies and in vivo animal models.

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Vitamin D as Radiosensitizer: A Review in Cell Line -

Journal of Pharmacy and Nutrition Sciences ◽

10.29169/1927-5951.2020.10.06.1 ◽

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.

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Bovine Organospecific Microvascular Endothelial Cell Lines as New and Relevant In Vitro Models to Study Viral Infections

International Journal of Molecular Sciences ◽

10.3390/ijms21155249 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5249 ◽

Cited By ~ 1

Author(s):

Anne-Claire Lagrée ◽

Fabienne Fasani ◽

Clotilde Rouxel ◽

Marine Pivet ◽

Marie Pourcelot ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Cell Lines ◽

T Antigen ◽

In Vitro Studies ◽

Microvascular Endothelial Cell ◽

Target Cells ◽

Microvascular Endothelial

Microvascular endothelial cells constitute potential targets for exogenous microorganisms, in particular for vector-borne pathogens. Their phenotypic and functional variations according to the organs they are coming from provide an explanation of the organ selectivity expressed in vivo by pathogens. In order to make available relevant tools for in vitro studies of infection mechanisms, our aim was to immortalize bovine organospecific endothelial cells but also to assess their permissivity to viral infection. Using transfection with SV40 large T antigen, six bovine microvascular endothelial cell lines from various organs and one macrovascular cell line from an umbilical cord were established. They display their own panel of endothelial progenitor/mature markers, as assessed by flow cytometry and RT-qPCR, as well as the typical angiogenesis capacity. Using both Bluetongue and foot-and-mouth disease viruses, we demonstrate that some cell lines are preferentially infected. In addition, they can be transfected and are able to express viral proteins such as BTV8-NS3. Such microvascular endothelial cell lines bring innovative tools for in vitro studies of infection by viruses or bacteria, allowing for the study of host-pathogen interaction mechanisms with the actual in vivo target cells. They are also suitable for applications linked to microvascularization, such as anti-angiogenic and anti-tumor research, growing fields in veterinary medicine.

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Antimyeloma Efficacy of Plitidepsin (Aplidin®): From Bench to the Bedside.

Blood ◽

10.1182/blood.v110.11.1178.1178 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1178-1178 ◽

Cited By ~ 1

Author(s):

Enrique M. Ocio ◽

Constantine Mitsiades ◽

M. Victoria Mateos ◽

Patricia Maiso ◽

Faustino Mollinedo ◽

...

Keyword(s):

Clinical Trial ◽

Cell Lines ◽

Single Agent ◽

In Vitro Studies ◽

Parp Cleavage ◽

Hematologic Toxicity ◽

Cell Transplant ◽

Significant Toxicity

Abstract Introduction Plitidepsin is a cyclic depsipeptide isolated from the marine tunicate, Aplidium albicans with promising antitumor activity. This work represents a comprehensive study (in vitro, in vivo and clinical) of its antimyeloma efficacy. Material & Methods In vitro studies were performed in 23 multiple myeloma (MM) cell lines and in cells from 16 MM patients. For the in vivo analysis a human plasmocytoma model in CB17-SCID mouse was used. Mice were randomized to receive Aplidin® 100 μg/Kg ip x 7 days/week (n=9), Aplidin® 140 μg/Kg ip x 5 days/week (n=7) or vehicle alone (n=9). The clinical efficacy of Aplidin® in relapsed/refractory patients was evaluated in a non-randomized two-stage Phase II, multicenter, clinical trial. Dosage of Aplidin® was 5 mg/m2 every 2 weeks. Results Aplidin® showed clear in vitro efficacy (IC50:1–10 nM) in the 23 cell lines tested including those resistant to dexamethasone, melphalan or doxorubicin. It was also active in the presence of microenvironment (IL-6, IGF-1 and BMSCs). Thirteen out of the 16 patient samples were sensitive to Aplidin® with >80% cell death in 8 cases and 60–80% in the remaining ones without significant toxicity in non tumor cells. Combination of Aplidin® with dexamethasone, bortezomib or lenalidomide showed clear potentiation. Aplidin® acts by inducing apoptosis with caspase−3, −7, −8, −9 and PARP cleavage. It also involves the activation of p38 and JNK signalling, Fas/CD95 translocation to lipid rafts and downregulation of Mcl-1 and myc. In mice studies, both schedules of treatment reduced tumor growth and increased survival with statistical differences in the group receiving 140 μg/Kg x 5d/week (p=0.04, Log Rank p=0.02). No significant toxicity was observed. These data provided the rationale for a clinical trial that has included 31 patients with relapsed/refractory MM. Median age was 65 years (47–82) and the median number of prior lines of therapy was 4 (range: 1–9) including autologous stem cell transplant (60%), thalidomide (58%) and bortezomib (48%). Out of the 26 evaluable patients, 2 (8%) achieved PR and 3 (12%) MR. Eight patients (31%) remained in stable disease (SD). Due to the synergism with dexamethasone observed in the in vitro studies, the protocol was amended to allow the addition of this agent in pts progressing after 3 cycles or with SD after 4 cycles. With a median follow-up of 14 months (range: 6.8–16.3), the time to progression in responding pts was 5.8 months (4.9–7.6). The most common G3-4 adverse events were fatigue (7%), serum creatine phosphokinase increase (7%), muscle toxicity (10%) and hepatic toxicity (10%). No significant hematologic toxicity or neuropathy was observed. Conclusion Aplidin® is effective both as a single agent and in combination with dexamethasone in the in vitro and in vivo settings. Its activity in relapsed/refractory MM patients is promising with an acceptable toxicity profile.

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NEUROPROTECTIVE AND COGNITIVE ENHANCING EFFECT OF METHANOLIC MORUS ALBA LEAF FRACTION IN U87MG CELL LINES AND EXPERIMENTAL RAT MODEL

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i4.32359 ◽

2019 ◽

pp. 238-243

Author(s):

ANJALI RAJ ◽

SUMIT DEY ◽

SUBBA RAO VENKATA MADHUNAPANTULA ◽

MANJULA SN

Keyword(s):

Cell Lines ◽

Neuronal Damage ◽

Morus Alba ◽

In Vitro Studies ◽

Potential Candidate ◽

Protective Effects ◽

U87mg Cell ◽

Standard Drug

Objective: The present study aims to investigate the protective effect of methanol fraction of Morus alba (MEMA) leaves against hydrogen peroxide (H2O2)-induced U87MG cell toxicity and aluminum fluoride (ALF)-induced rat toxicity. Methods: The study was divided into in vitro and in vivo sections. U87MG cell lines were pre-treated with different fractions of MEMA for 20 h and further tested against 1000 ϻM of H2O2. The best fraction from in vitro studies was used to study the protective effects against ALF-induced neurotoxicity. Rats were divided i nto five different groups, and MEMA (200 and 400 mg/kg p.o) was administered for 14 days to the animals with α-tocopherol as the standard drug treatment. Behavioral studies were assessed using Barnes maze. The major biochemical measurements included catalase, superoxide dismutase and glutathione reductase, lipid peroxidation (LPO), and acetylcholinesterase (AchE) levels. Results: In vitro studies indicated MEMA as a potential candidate followed by AQMA and ethyl acetate. The MEMA fraction was able to ameliorate ALF-induced neurotoxicity in the behavioral assessment. The higher antioxidant content in the fraction decreased the LPO levels from 250±4.07 to 115±3.22 as well as elevated the levels of most of the endogenous antioxidant enzyme levels. AchE levels were also decreased to 33.89±0.71 from 38.94±0.64. Conclusion: Although the results obtained indicate that MEMA could significantly suppress oxidative stress-induced central neuronal damage both in vitro and in vivo, further mechanistic studies are required to delineate its neuroprotective pathway.

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Anticancer Potential of Betulonic Acid Derivatives

International Journal of Molecular Sciences ◽

10.3390/ijms22073676 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3676

Author(s):

Adelina Lombrea ◽

Alexandra Denisa Scurtu ◽

Stefana Avram ◽

Ioana Zinuca Pavel ◽

Māris Turks ◽

...

Keyword(s):

Anticancer Agents ◽

Betulonic Acid ◽

Pharmacological Activities ◽

Cellular Resistance ◽

Drug Candidates ◽

Starting Point ◽

Derivatives Of ◽

Biological And Pharmacological Activities

Clinical trials have evidenced that several natural compounds, belonging to the phytochemical classes of alkaloids, terpenes, phenols and flavonoids, are effective for the management of various types of cancer. Latest research has proven that natural products and their semisynthetic variants may serve as a starting point for new drug candidates with a diversity of biological and pharmacological activities, designed to improve bioavailability, overcome cellular resistance, and enhance therapeutic efficacy. This review was designed to bring an update regarding the anticancer potential of betulonic acid and its semisynthetic derivatives. Chemical derivative structures of betulonic acid including amide, thiol, and piperidine groups, exert an amplification of the in vitro anticancer potential of betulonic acid. With the need for more mechanistic and in vivo data, some derivatives of betulonic acids may represent promising anticancer agents.

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

Blood ◽

10.1182/blood.v114.22.4925.4925 ◽

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.

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Abnormal Sensitivity of Cortisol-Producing Adrenocortical Adenomas to Serotonin: In Vivo and in Vitro Studies

Yearbook of Endocrinology ◽

10.1016/s0084-3741(08)70169-0 ◽

2007 ◽

Vol 2007 ◽

pp. 358-361

Author(s):

D.E. Schteingart

Keyword(s):

In Vitro Studies ◽

Adrenocortical Adenomas

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The Venom of the Boomslang (Dispholidus Typus): In Vivo and in Vitro Studies

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653532 ◽

1969 ◽

Vol 21 (02) ◽

pp. 234-244 ◽

Cited By ~ 5

Author(s):

N Mackay ◽

J.C Ferguson ◽

Antonia Bagshawe ◽

A.T.T Forrester ◽

G.P Mcnicol

Keyword(s):

In Vitro Studies

SummaryAn account is given of the effects of boomslang venom in man. Evidence was found of a fibrinolytic state apparently secondary to the coagulant action of the venom. These features rapidly responded to the administration of specific antivenom. In vitro studies, using a homogenate of boomslang parotids, confirmed the coagulant properties of the venom and showed them to be of much greater potency than the proteolytic actions.

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