scholarly journals Thujone-Rich Fraction ofThuja occidentalisDemonstrates Major Anti-Cancer Potentials: Evidences fromIn VitroStudies on A375 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Raktim Biswas ◽  
Sushil Kumar Mandal ◽  
Suman Dutta ◽  
Soumya Sundar Bhattacharyya ◽  
Naoual Boujedaini ◽  
...  
Keyword(s):  
Cell Line ◽  
Ethanolic Extract ◽  
Ros Generation ◽  
Molecular Formula ◽  
Minimal Growth ◽  
Peripheral Blood Mononuclear ◽  
Thuja Occidentalis ◽  
Anti Cancer ◽  
A375 Cells

Crude ethanolic extract ofThuja occidentalis(Fam: Cupressaceae) is used as homeopathic mother tincture (TOΦ) to treat various ailments, particularly moles and tumors, and also used in various other systems of traditional medicine. Anti-proliferative and apoptosis-inducing properties of TOΦ and the thujone-rich fraction (TRF) separated from it have been evaluated for their possible anti-cancer potentials in the malignant melanoma cell line A375. On initial trial byS-diphenyltetrazolium bromide assay, both TOΦ and TRF showed maximum cytotoxic effect on A375 cell line while the other three principal fractions separated by chromatography had negligible or no such effect, because of which only TRF was further characterized and subjected to certain other assays for determining its precise anti-proliferative and apoptotic potentials. TRF was reported to have a molecular formula of C10H16O with a molecular weight of 152. Exposure of TRF ofThuja occidentalisto A375 cellsin vitroshowed more cytotoxic, anti-proliferative and apoptotic effects as compared with TOΦ, but had minimal growth inhibitory responses when exposed to normal cells (peripheral blood mononuclear cell). Furthermore, both TOΦ and TRF also caused a significant decrease in cell viability, induced inter-nucleosomal DNA fragmentation, mitochondrial transmembrane potential collapse, increase in ROS generation, and release of cytochromecand caspase-3 activation, all of which are closely related to the induction of apoptosis in A375 cells. Thus, TRF showed and matched all the anti-cancer responses of TOΦ and could be the main bio-active fraction. The use of TOΦ in traditional medicines against tumors has, therefore, a scientific basis.

scholarly journals Diverse Effects of Different “Protein-Based” Vehicles on the Stability and Bioavailability of Curcumin: Spectroscopic Evaluation of the Antioxidant Activity and Cytotoxicity In Vitro

2019 ◽  
Vol 26 (2) ◽  
pp. 132-147 ◽  
Author(s):  
Farideh Mirzaee ◽  
Leila Hosseinzadeh ◽  
Mohammad Reza Ashrafi-Kooshk ◽  
Sajjad Esmaeili ◽  
Sirous Ghobadi ◽  
...  
Keyword(s):  
Cell Line ◽  
Water Solubility ◽  
Neuroblastoma Cell ◽  
Ros Generation ◽  
Human Neuroblastoma Cell ◽  
Breast Carcinoma Cell Line ◽  
Human Neuroblastoma ◽  
Anti Cancer ◽  
Cancer Activity

Background: Curcumin is a natural polyphenolic compound with anti-cancer, antiinflammatory, and anti-oxidation properties. Low water solubility and rapid hydrolytic degradation are two challenges limiting use of curcumin. </P><P> Objective: In this study, the roles of the native/modified forms of Bovine Serum Albumin (BSA), &#946;-lactoglobulin (&#946;-lg) and casein, as food-grade biopolymers and also protein chemical modification, in stabilizing and on biological activity of curcumin were surveyed. </P><P> Methods: In this article, we used various spectroscopic as well as cell culture-based techniques along with calculation of thermodynamic parameters. </P><P> Results: Investigation of curcumin stability indicated that curcumin binding to the native BSA and modified &#946; -lg were stronger than those of the modified BSA and native &#946; -lg, respectively and hence, the native BSA and modified &#946;-lg could suppress water-mediated and light-mediated curcumin degradation, significantly. Moreover, in the presence of the native proteins (BSA and casein), curcumin revealed elevated in vitro anti-cancer activity against MCF-7 (human breast carcinoma cell line) and SKNMC (human neuroblastoma cell line). As well, curcumin, in the presence of the unmodified “BSA and &#946;-lg”, was more potent to decrease ROS generation by hydrogen peroxide (H2O2) whereas it led to an inverse outcome in the presence of native casein. Overall, in the presence of the protein-bound curcumin, increased anti-cancer activity and decreased ROS generation by H2O2 in vitro were documented. </P><P> Conclusion: It appears that “water exclusion” is major determinant factor for increased stability/ efficacy of the bound curcumin so that some protein-curcumin systems may provide novel tools to increase both food quality and the bioavailability of curcumin as health promoting agent.

Design, Synthesis and In Vitro Anti-Cancer Evaluation of Novel Derivatives of 2-(2-Methyl-1,5-diaryl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3- yl)acetamide

2020 ◽  
Vol 16 (3) ◽  
pp. 340-349
Author(s):  
Ebrahim S. Moghadam ◽  
Farhad Saravani ◽  
Ernest Hamel ◽  
Zahra Shahsavari ◽  
Mohsen Alipour ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Peripheral Neuropathy ◽  
Cell Line ◽  
Normal Cell ◽  
Caspase 3 ◽  
Annexin V ◽  
Normal Cell Line ◽  
Anti Cancer ◽  
Mcf 7

Objective: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage. Methods: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay. Results: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100 μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3. Conclusion: Newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial.

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.

Head and Neck Squamous Cell Carcinoma Cell Line-Induced Suppression of in vitro Lymphocyte Proliferative Responses

1992 ◽  
Vol 106 (2) ◽  
pp. 149-158 ◽  
Author(s):  
Henry Lapointe ◽  
Howard Lampe ◽  
Diponkar Banerjee
Keyword(s):  
Squamous Cell Carcinoma ◽  
Peripheral Blood Mononuclear Cell ◽  
Tumor Cell ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Line ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Peripheral Blood Mononuclear

Tumour-infiltrating lymphocytes (TILS) are often difficult to expand in vitro. In some cases this has been attributable to immunosuppression mediated by the elaboration of prostaglandins by either tumor cells or tumor-infiltrating monocytes. In this laboratory, freshly prepared TILs containing single-cell suspensions of head and neck tumors displayed both poor proliferation as well as minimal responsiveness to indomethacin-mediated reversal of immunosuppression. In order to investigate tumor-mediated immunosuppression further, a system was developed whereby a new cell line of head and neck squamous cell carcinoma was used to suppress allogeneic peripheral blood mononuclear cell proliferation in response to phytohemagglutinin (PHA) and interieukin-2 (IL-2). Tumor cells were able to suppress peripheral blood mononuclear cell (PBMNC) proliferation up to 95%. This suppressive effect was dependent on tumor cell number and was reversible by the use of higher concentrations of PHA, but not by increased concentrations of IL-2. Suppression was immediate when IL-2 was used as the stimulus for proliferation, but required extended lymphocyte/tumor cell contact when PHA was used. Flow cytometric analysis of tumor-exposed and PHA-stimulated PBMNCs revealed a decrease in both the number of cells expressing IL-2 receptors as well as the density of IL-2 receptors per cell. This pattern of suppression, as well as the reversibility of suppression by indomethacin, implicates prostaglandins in the mechanisms by which these tumor cells mediate immunosuppression.

Glucosylceramide Synthetase Inhibitors Sensitise B-CLL Cells to Cytotoxic Agents without Reversing P-gp Functional Activity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1181-1181
Author(s):  
Gareth Gerrard ◽  
Terry D. Butters ◽  
Atul B. Mehta ◽  
A. Victor Hoffbrand ◽  
Derryln Hughes ◽  
...  
Keyword(s):  
Cell Line ◽  
Functional Activity ◽  
Mononuclear Cells ◽  
Efflux Pump ◽  
Specific Inhibitor ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Drugs ◽  
Cytotoxic Agents ◽  
Peripheral Blood Mononuclear

Abstract Malignant B-cells from a high proportion of chronic lymphocytic leukaemia (B-CLL) patients over express the multidrug resistance (MDR) -1 gene encoded transmembrane efflux pump P-glycoprotein (P-gp). Inhibition of glucosylceramide synthesis has been shown to correlate with the expression and function of P-gp and sensitise cells to cytotoxic agents. We analysed the ability of glucosylceramide synthetase (GCS) inhibitors N-butyl-deoxygalactonojirimycin (OGB-1, 500μM) and N-nonyl-deoxygalactonojirimycin (OGB-2, 100μM) to sensitise B-CLL cells to conventional cytotoxic drugs 2-chlorodeoxyadenosine (CdA), chlorambucil (Chl) and fludarabine (FdR) using the in vitro cytotoxicity MTT assay. The effect on P-gp activity was also analysed using the calcein-AM accumulation assay and the results expressed as multidrug activity factor (MAF), where a MAF of &gt;10 in the presence of a P-gp inhibitor denotes P-gp functional activity. GCS inhibitors were cultured with B-CLL cells for 24-48h before the assays were performed. The P-gp negative cell line CEM-CCRF had no MAF activity with an IC50 for vincristine (a known P-gp substrate) of &lt;1ng/ml. The P-gp over expressing cell line CEM-VLB showed a MAF value of 96.4 with zosuquidar trihydrochloride (Z.3HCL), a specific inhibitor of P-gp, 15.7 with OGB-1 and 45.9 with OGB-2. The IC50 for vincristine was reduced from &gt;10ug/ml to 55.5ng/ml in the presence of OGB-2. In peripheral blood mononuclear cells from 3 normal volunteers (all P-gp +ve), the mean MAF value for Z.3HCL was 23.86 and for OGB-2 was 16.2. In 9/13 B-CLL samples there was P-gp functional activity in the presence of Z.3HCL with a mean MAF value of 22.15 (range 11.27–37.3). P-gp was over expressed in10/13 B-CLL samples. However, when available samples from this cohort were assessed with OGB-1 (n=4) and OGB-2 (n=13) the MAF value was &lt;10. Nevertheless, sensitisation of B-CLL cells was observed by a reduction in the IC50 in the presence of OGB-1 with CdA in 3/4 (to 40% in the presence of cytotoxic drug alone), Chl in 3/4 (39%), FdR in 2/4 (26%) and in the presence of OGB-2 with CdA in 8/13 (42%), Chl in 5/13 (40%) and FdR in 7/13 (34%). Although GCS inhibitors sensitize B-CLL cells to cytotoxic drugs in some B-CLL patients, they do not appear to have any effect on P-gp functional activity.

Activity of NEO2734, a novel dual inhibitor of both BET and CBP-P300, in SPOP-mutated prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 62-62 ◽  
Author(s):  
Yuqian Yan ◽  
Dejie Wang ◽  
Jian Ma ◽  
Xiaodong Pang ◽  
Dong Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Clinical Studies ◽  
Nature Medicine ◽  
Dual Inhibitor ◽  
Bet Inhibitor ◽  
Working Models ◽  
Anti Cancer

62 Background: We have previously reported that mutations in SPOP promote bromodomain and extra-terminal motif (BET) protein upregulation and BET inhibitor resistance in prostate cancer (Zhang et al., Nature Medicine 23(9):1055-1062, 2017). Other studies indicate that histone acetyltransferases (HATs) such as P300 are also upregulated in SPOP-mutated prostate cancer (Blattner et al., Cancer Cell 31: 436-451, 2017). Methods: We examined the anti-cancer effect of NEO2734 (Epigene Therapeutics Inc), a novel dual inhibitor of both BET and CBP-P300, in prostate cancer using cell line, organoid and patient-derived xenografts (PDX) as working models. We examined the anti-cancer effect of NEO2734 (Epigene Therapeutics Inc), a novel dual inhibitor of both BET and CBP-P300, in prostate cancer using cell line, organoid and patient-derived xenografts (PDX) as working models. Results: We demonstrated that while prostate cancer cell lines expressing F133V, the most frequent SPOP mutant, are very resistant to both BET inhibitor JQ1 and CBP/P300 inhibitor CPI-637, they are very sensitive to simultaneous cotreatment with JQ1 and CPI-637. Similarly, we demonstrated that F133V mutant cells are also very sensitive to NEO2734. We established PDX and organoid models from a patient with prostate cancer expressing a novel SPOP mutation Q165P. Computer simulation analysis reveals that the Q165P mutation causes larger conformational fluctuation, indicating that the structure of Q165P is less stable than that of wild type SPOP. Accordingly, co-immunoprecipitation assay showed that Q165P mutation impaired the dimerization ability of SPOP. We further showed that the Q165P mutant organoid was very sensitive to NEO2734 in vitro and the Q165P mutant PDX was very sensitive to NEO2734 in mice. Conclusions: These PDX-based pre-clinical studies indicate that the inhibition of both BET and CBP-P300, either by co-administration of two agents, or by treatment with the dual inhibitor, NEO2734, is effective in SPOP-mutated prostate cancer. These data provide a strong rationale for the inclusion of patients with SPOP-mutated prostate cancer in clinical studies of NEO2734.

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