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Antiglycolytic Activities of Strobilanthes crispus Active Fraction and its Bioactive Components on Triple-Negative Breast Cancer Cells In Vitro

Muhammad SNH, Yaacob NS, Safuwan NAM, Fauzi AN

Anticancer Agents Med Chem, 2021 Apr 26.
PMID: 33906591 DOI: 10.2174/1871520621666210427104804

BACKGROUND: Survival and progression of cancer cells are highly dependent on aerobic glycolysis. Strobilanthes crispus has been shown to have promising anticancer effects on breast cancer cells. The involvement of the glycolysis pathway in producing these effects is unconfirmed, thus further investigation is required to elucidate this phenomenon.
OBJECTIVE: This study aims to determine the effect of S. crispus active fraction (F3) and its bioactive components on glycolysis in triple-negative breast cancer cells (MDA-MB-231).
METHODS: This study utilizes F3, lutein, β-sitosterol, and stigmasterol to be administered in MDA-MB-231 cells for measurement of antiglycolytic activities through cell poliferation, glucose uptake, and lactate concentration assays. Cell proliferation was assessed by MTT assay of MDA-MB-231 cells after treatment with F3 and its bioactive components lutein, β-sitosterol, and stigmasterol. The IC50 value in each compound was determined by MTT assay to be used in subsequent assays. The determination of glucose uptake activity and lactate concentration were quantified using fluorescence spectrophotometry.
RESULTS: Antiproliferative activities were observed for F3 and its bioactive components, with IC50 values of 100 µg/mL (F3), 20 µM (lutein), 25 µM (β-sitosterol), and 90 μM (stigmasterol) in MDA-MB-231 cells at 48 h. The percentage of glucose uptake and lactate concentration in MDA-MB-231 cells treated with F3, lutein, or β sitosterol were significantly lower than those observed in the untreated cells in a time-dependent manner. However, treatment with stigmasterol decreased the concentration of lactate without affecting the glucose uptake in MDA-MB-231 cells.
CONCLUSION: The antiglycolytic activities of F3 on MDA-MB-231 cells are attributed to its bioactive components.

Matched MeSH terms: Cell Proliferation
Fulltext Computational prediction of miR130a target genes in cancer

Nur Ainina Abdollah, Nurulisa Zulkifle, Siti Razila Abdul Razak

Malaysian Journal of Medicine and Health Sciences, 2020;16(102):51-59.
MyJurnal

Introduction: Cancer is one of the main causes of mortality globally and the incidence has been rising over the years. Studies have shown that miRNAs have the potential as cancer biomarkers. The miR-130a has been reported to be upregulated in several types of cancer, which indicate the important roles of miR-130a in cancer development and metastasis. The aim of this study is to identify potential target genes and to predict the regulatory function of miR- 130a-3p and 5p in cancer. Methods: Three bioinformatics platforms namely miRWalk, the Database for annotations, visualization and integrated discovery (DAVID) Gene Functional Classification Tool and miRanda-miRSVR analysis tools were used to identify possible interaction between miR-130a and its target. Protein-protein interaction (PPI) network for the predicted target genes was then constructed. Results: The analyses have identified nine predicted target genes for miR-130a-3p (RAPGEF4, SOS2, NRP1, RPS6KB1, MET, IL15, ACVR1, RYR2 and ITPR1), and ten for miR-130a-5p (BCL11A, SPOPL, NLK, PPARGC1A, POU4F2, CPEB4, ST18, RSBN1L, ELF5 and ARID4B), that might
play an important role in the development of cancer. Findings from this report suggest that miR-130a may involves in controlling cancer related genes; MET, ACVR1 and BCL11A. miR-130a-3p may regulates MET which involves in apoptosis and metastasis, and ACVR1 which involves in metastasis and angiogenesis. miR-130a-5p may regulates BCL11A which involves in apoptosis, proliferation and tumorigenesis. Conclusion: This study has highlighted the molecular interaction of miR-130a with associated genes and pathways, suggesting therapeutic potential of miR- 130a as personalised targeted therapy for cancer.

Matched MeSH terms: Cell Proliferation
Effect of photobiomodulation therapy on inflammatory cytokines in healing dynamics of diabetic wounds: a systematic review of preclinical studies

Karkada G, Maiya GA, Houreld NN, Arany P, Rao Kg M, Adiga S, et al.

Arch Physiol Biochem, 2020 Dec 28.
PMID: 33370535 DOI: 10.1080/13813455.2020.1861025

CONTEXT: Delayed wound healing in diabetes mellitus (DM) is due to the overlapping phases of the healing process. The prolonged inflammation and altered levels of inflammatory cytokines lead to deformed cell proliferation. Photobiomodulation alleviates the expression of inflammatory cytokines and promotes tissue repair, thereby restoring the wound healing process.
OBJECTIVE: To find out the effect of photobiomodulation therapy (PBMT) in the healing dynamics of diabetic wounds with particular emphasis on interleukin-6, interleukin-1β, and tumour necrosis factor-α.
METHODS: Scientific databases searched using keywords of the population: DM, intervention: PBMT, and outcomes: inflammatory cytokines.
RESULTS: We have included five preclinical studies in the present systematic review for qualitative analysis. These studies evaluated the effect of PBMT at different wavelengths, dosage, and time on wound healing in DM.
CONCLUSIONS: The systematic review concludes that PBMT regulates inflammatory cytokines levels, enhances cell proliferation, and migration, thereby improving the wound healing properties.

Matched MeSH terms: Cell Proliferation
Fulltext Cytotoxicity of leukemic cells by nypa fruticans through regulation of adiponectin expression

Mohammad Fauzan Zainudin, Ummu Afifah Fadzir, Athirah Rosdi, Muhammad Farid Johan, Ridzwan Hashim, Ridhwan Abdul Wahab, et al.

International Journal of Allied Health Sciences, 2017;1(2):28-43.
MyJurnal

Acute lymphoblastic leukemia (ALL) is the most common leukemia subtypes among paediatrics in Malaysia. Although treatment options are available but some patients remain incurable, some undergo relapse and many experiences adverse effects by the conventional therapies. Thus, we aim to investigate possible treatment alternative by studying the antileukemogenesis properties of concentrated Nypa fruticans sap called nisaan by focusing on adiponectin expression.
Our study model was CCRF-CEM, an acute lymphoblastic leukemia cell lines. The cells were treated with nisaan at a range of concentration and treated for 24, 48 and 72 hours followed by determination of the leukemic cells viability using tryphan blue method. Effective nisaan concentrations that significantly reduced the cells viability were again treated to the cells followed by determination of the cell proliferation using BrdU colorimetric kit and adiponectin level using adiponectin ELISA kit.
The results showed that, increase concentration of nisaan treatment reduced the cells viability and cells proliferation and enhance the adiponectin level in the leukemic cells.
This preliminary data suggest that Nypa fruticans might has the antileukemogenesis effect on acute lymphoblastic cells by regulating the adiponectin expression.

Matched MeSH terms: Cell Proliferation
Fulltext Insights into the Role of microRNAs in Colorectal Cancer (CRC) Metabolism

Wai Hon K, Zainal Abidin SA, Othman I, Naidu R

Cancers (Basel), 2020 Aug 31;12(9).
PMID: 32878019 DOI: 10.3390/cancers12092462

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, with a high mortality rate globally. The pathophysiology of CRC is mainly initiated by alteration in gene expression, leading to dysregulation in multiple signalling pathways and cellular processes. Metabolic reprogramming is one of the important cancer hallmarks in CRC, which involves the adaptive changes in tumour cell metabolism to sustain the high energy requirements for rapid cell proliferation. There are several mechanisms in the metabolic reprogramming of cancer cells, such as aerobic glycolysis, oxidative phosphorylation, lactate and fatty acids metabolism. MicroRNAs (miRNAs) are a class of non-coding RNAs that are responsible for post-transcriptional regulation of gene expression. Differential expression of miRNAs has been shown to play an important role in different aspects of tumorigenesis, such as proliferation, apoptosis, and drug resistance, as well as metabolic reprogramming. Increasing evidence also reports that miRNAs could function as potential regulators of metabolic reprogramming in CRC cells. This review provides an insight into the role of different miRNAs in regulating the metabolism of CRC cells as well as to discuss the potential role of miRNAs as biomarkers or therapeutic targets in CRC tumour metabolism.

Matched MeSH terms: Cell Proliferation
Large-Scale Expansion of Human Mesenchymal Stem Cells

Hassan MNFB, Yazid MD, Yunus MHM, Chowdhury SR, Lokanathan Y, Idrus RBH, et al.

Stem Cells Int, 2020;2020:9529465.
PMID: 32733574 DOI: 10.1155/2020/9529465

Mesenchymal stem cells (MSCs) are multipotent stem cells with strong immunosuppressive property that renders them an attractive source of cells for cell therapy. MSCs have been studied in multiple clinical trials to treat liver diseases, peripheral nerve damage, graft-versus-host disease, autoimmune diseases, diabetes mellitus, and cardiovascular damage. Millions to hundred millions of MSCs are required per patient depending on the disease, route of administration, frequency of administration, and patient body weight. Multiple large-scale cell expansion strategies have been described in the literature to fetch the cell quantity required for the therapy. In this review, bioprocessing strategies for large-scale expansion of MSCs were systematically reviewed and discussed. The literature search in Medline and Scopus databases identified 26 articles that met the inclusion criteria and were included in this review. These articles described the large-scale expansion of 7 different sources of MSCs using 4 different bioprocessing strategies, i.e., bioreactor, spinner flask, roller bottle, and multilayered flask. The bioreactor, spinner flask, and multilayered flask were more commonly used to upscale the MSCs compared to the roller bottle. Generally, a higher expansion ratio was achieved with the bioreactor and multilayered flask. Importantly, regardless of the bioprocessing strategies, the expanded MSCs were able to maintain its phenotype and potency. In summary, the bioreactor, spinner flask, roller bottle, and multilayered flask can be used for large-scale expansion of MSCs without compromising the cell quality.

Matched MeSH terms: Cell Proliferation
Immunosuppressive and hepatoprotective potential of Sarcococca saligna and its biomarker components

Ali H, Musharraf SG, Iqbal N, Adhikari A, Abdalla OM, Ahmed Mesaik M, et al.

Int Immunopharmacol, 2015 Sep;28(1):235-43.
PMID: 26093268 DOI: 10.1016/j.intimp.2015.06.009

Sarcococca saligna methanolic extract, fractions and isolated pure compounds saracocine (1), saracodine (2), pachyximine-A (3) and terminaline (4) were found to possess potent immunosuppressive activities. The fractions and compounds were tested in-vitro for their effects on human T-cell proliferation, and cytokine (IL-2) production. All the fractions, sub-fractions and purified compounds showed significant suppressive effect on IL-2 production in a dose-dependent manner. They also exhibited a suppressive effect on the phytohemagglutinin-stimulated T-cell proliferation. None of the extracts and purified compounds showed any cytotoxicity effects on the 3T3 mice fibroblast cell line. The crude extract, DCM fraction (pH9), DCM fractions (pH7) and one of the steroidal alkaloids (terminaline) were checked in-vivo for their hepato-protective potential against CCl4-induced liver injury. In in-vivo experiments, the basic and neutral DCM fractions and terminaline (4) significantly reduced inflammation in the liver. DCM fraction (pH9), DCM fractions (pH7) and compound 4 reduced the serum enzyme levels (ALT, AST, and ALP) down to control levels despite CCl4 treatment. They also reduced the CCl4-induced damaged area to almost zero as assessed by histopathology. The pale necrotic areas and mixed inflammatory infiltrate which are seen after CCl4 treatment were absent in the cases of basic, neutral fractions and terminaline treatment. These hepato-protective effects were better than the positive control silymarin. Our results suggest the therapeutic effect of S. saligna extract, fractions and bioactive steroidal alkaloids against CCl4-induced liver injury in vivo and their immunosuppressive function in vitro.

Matched MeSH terms: Cell Proliferation
Fulltext Cell proliferation assessment of human gingival fibroblasts treated with Clinacanthus nutans using alamarBlue assay

Kelvin Yong Pui Szi, Wan Afiqah Syahirah Wan Ghazali, Siti Fadilah Abdullah, Norzaliana Zawawi, Thirumulu Ponnuraj Kannan

Archives of Orofacial Sciences, 2018;13(2):1-6.
MyJurnal

Clinacanthus nutans (C. nutans), a well-known ethnopharmacological plant consumed for its medicinal purposes by Southeast Asian communities. C. nutans is said to possess antipyretic, inflammatory, antiedemic as well as analgesic properties and used traditionally in treating various skin ailments, Herpes infection, cancer and diabetes. The young leaves of this C. nutans are consumed in Malaysia for maintaining health. In this study, the proliferative activity of human gingival fibroblast cells (HGF-1, ATCC®CRL-2014™, USA) treated with the ethanol extract obtained from C. nutans leaves at three different concentrations (250, 125 and 62.5 µg/ml) was compared with the untreated cells using alamarBlue assay. The proliferative activity of HGF-1 using alamarBlue assay showed that the cells treated with 62.5 μg/ml of ethanolic extract of C. nutans leaves exhibited increased proliferation compared to the other groups and hence does not exhibit any cytotoxicity on HGF-1.

Matched MeSH terms: Cell Proliferation
Surface modification and bioactivity of anodic Ti6Al4V alloy

Saharudin KA, Sreekantan S, Abd Aziz SN, Hazan R, Lai CW, Mydin RB, et al.

J Nanosci Nanotechnol, 2013 Mar;13(3):1696-705.
PMID: 23755576

The present study deals with surface modification of Ti6Al4V alloy via anodization technique. The morphology, structure, adhesion and bioactivity of Ti6Al4V alloy after anodization process were investigated in detail. The influence of fluoride content and direct circuit (DC) applied voltage during anodization of Ti6Al4V alloy in a bath with electrolytes composed of ethylene glycol (EG) and ammonium fluoride (NH4F) were considered. It was found that the average pore sizes and length of nanoporous or nanotubes were increasing with the fluoride content and applied voltage. A minimum of 3 wt% of NH4F is required to grow a self-organized nanotube arrays. As the fluoride content was increased to 5 wt%, TiO2 nanotubes with average diameter of 110 nm and 3.4 microm lengths were successfully synthesized. It is noteworthy to point out that the rate of the nanotube formation was increasing up to 9 microm thick bioactive TiO2 nanotubes layer as anodization time was increased to 3 h. Based on the results obtained, the PA6 cells cultured on anodic Ti6Al4V alloy showed highest level of cell viability and greater cell adhesion compared to the flat Ti6Al4V foil substrate. In fact, highly ordered nanotubes structure on Ti6Al4V alloy can provide beneficial effects for PA6 cells in attachment and proliferation.

Matched MeSH terms: Cell Proliferation
Fulltext The effect of DMEM and DMEM:F12 culture media on the growth of SH-SY5Y cells

Aishah Mohammed Izham, Min, Jasmine Chia Siew, Vidyadaran, Sharmili, Mohd Roslan Sulaiman, Hemabarathy, Bharatham B., Perimal, Enoch Kumar

Life Sciences, Medicine and Biomedicine, 2018;2(3):6-0.
MyJurnal

The human neuroblastoma cell line, SH-SY5Y cells, derived from the parental SK-N-SH cell line, is commonly used as an in vitro model for neuroscience and neurobiology research. Since SH-SY5Y cells are widely cultured for research, several different culture media have been used to optimize the growth of the cells, including Eagle's Minimum Essential Medium (EMEM), Dulbecco’s modified Eagle’s medium (DMEM) and other recently developed culture media. SH-SY5Y cells has the ability to reach confluency in culture flasks ranges from 5 days to 15 days, depending on the culture media used. Hence, the optimization of the culture media is crucial to achieve the fastest growth rate for the cells. The objective of the study is to evaluate the culture media for the proliferation of SH-SY5Y cells. We compared the growth rate of SH-SY5Y cells cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 15% heat-inactivated fetal bovine serum (hiFBS), Dulbecco’s modified Eagle’s medium: Nutrient mixture F-12 (DMEM:F12) + supplemented with 15% hiFBS and DMEM:F12 supplemented with 10% hiFBS. In DMEM:F12 supplemented with 15% hiFBS, cells grew up to 6.67E+05 cells. In DMEM:F12 supplemented with 10% hiFBS, cells grew up to 5.28E+05 cells. In DMEM supplemented with 15% hiFBS, the cells grew up to 4.76E+05 cells. There was a significant difference between culture media DMEM:F12 supplemented with 15% hiFBS as compared to DMEM:F12 supplemented with 10%hiFBS and DMEM supplemented with 15% hiFBS (p0.05). We found that DMEM:F12 supplemented with 15% hiFBS could serve as an optimized culture media for high proliferation rate of SH-SY5Y cells.

Matched MeSH terms: Cell Proliferation
Catharanthus roseus Aqueous Extract is Cytotoxic to Jurkat Leukaemic T-cells but Induces the Proliferation of Normal Peripheral Blood Mononuclear Cells

Ahmad NH, Rahim RA, Mat I

Trop Life Sci Res, 2010 Dec;21(2):101-13.
PMID: 24575203

Research on natural products has been widely used as a strategy to discover new drugs with potential for applications in complementary medicines because they have fewer side effects than conventional drugs. The aim of the present study was to evaluate the in vitro cytotoxic effects of crude aqueous Catharanthus roseus extract on Jurkat cells and normal peripheral blood mononuclear cells (PBMCs). The aqueous extract was standardised to vinblastine by high performance liquid chromatography (HPLC) and was used to determine cytotoxicity by the MTS [3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. DNA fragmentation assay was employed to determine if cell death was due to apoptosis. The results showed that the aqueous extract induced cell death of Jurkat cells at 24, 48 and 72 hours post-treatment in a time- and dose-dependent manner. However, cells treated at 48 and 72 hours produced higher cytotoxic effects with half maximal inhibitory concentration (IC50) values of 2.55 μg/ml and 2.38 μg/ml, respectively. In contrast, the extract induced normal PBMC proliferation, especially after 24 hours treatment with 1000 μg/ml. This result indicates that the C. roseus crude aqueous extract showed differential effects of inhibiting the proliferation of the Jurkat cell line and promoting the growth of PBMCs. These data suggest that the extract may be applicable for modulating the normal and transformed immune cells in leukaemia patients.

Matched MeSH terms: Cell Proliferation
Single Agent and Synergistic Activity of Maritoclax with ABT-263 in Nasopharyngeal Carcinoma (NPC) Cell Lines

Xiang BLS, Kwok-Wai L, Soo-Beng AK, Mohana-Kumaran N

Trop Life Sci Res, 2020 Oct;31(3):1-13.
PMID: 33214852 DOI: 10.21315/tlsr2020.31.3.1

The BCL-2 anti-apoptotic proteins are over-expressed in many cancers and hence are attractive therapeutic targets. In this study, we tested the sensitivity of two Nasopharyngeal Carcinoma (NPC) cell lines HK1 and C666-1 to Maritoclax, which is reported to repress anti-apoptotic protein MCL-1 and BH3 mimetic ABT-263, which selectively inhibits anti-apoptotic proteins BCL-2, BCL-XL and BCL-w. We investigated the sensitisation of the NPC cell lines to these drugs using the SYBR Green I assay and 3D NPC spheroids. We report that Maritoclax repressed anti-apoptotic proteins MCL-1, BCL-2, and BCL-XL in a dose- and time-dependent manner and displayed a single agent activity in inhibiting cell proliferation of the NPC cell lines. Moreover, combination of Maritoclax and ABT-263 exhibited synergistic antiproliferative effect in the HK1 cells. Similar results were obtained in the 3D spheroids generated from the HK1 cells. More notably, 3D HK1 spheroids either treated with single agent Maritoclax or combination with ABT-263, over 10 days, did not develop resistance to the treatment rapidly. Collectively, the findings illustrate that Maritoclax as a single agent or combination with BH3 mimetics could be potentially useful as treatment strategies for the management of NPC.

Matched MeSH terms: Cell Proliferation
Fulltext Cytotoxicity of snake venom enzymatic toxins: phospholipase A2 and l-amino acid oxidase

Hiu JJ, Yap MKK

Biochem Soc Trans, 2020 04 29;48(2):719-731.
PMID: 32267491 DOI: 10.1042/BST20200110

The phospholipase A2 (PLA2) and l-amino acid oxidase (LAAO) are two major enzymes found in the venoms from most snake species. These enzymes have been structurally and functionally characterised for their pharmacological activities. Both PLA2 and LAAO from different venoms demonstrate considerable cytotoxic effects on cancer cells via induction of apoptosis, cell cycle arrest and suppression of proliferation. These enzymes produce more pronounced cytotoxic effects in cancer cells than normal cells, thus they can be potential sources as chemotherapeutic agents. It is proposed that PLA2 and LAAO contribute to an elevated oxidative stress due to their catalytic actions, for instance, the ability of PLA2 to produce reactive oxygen species during lipolysis and formation of H2O2 from LAAO catalytic activity which consequently lead to cell death. Nonetheless, the cell-death signalling pathways associated with exposure to these enzymatic toxins are not fully elucidated yet. Here in this review, we will discuss the cytotoxic effects of PLA2 and LAAO in relationship to their catalytic mechanisms and the underlying mechanisms of cytotoxic actions.

Matched MeSH terms: Cell Proliferation
Fulltext Co-inhibition of BCL-XL and MCL-1 with selective BCL-2 family inhibitors enhances cytotoxicity of cervical cancer cell lines

Abdul Rahman SF, Muniandy K, Soo YK, Tiew EYH, Tan KX, Bates TE, et al.

Biochem Biophys Rep, 2020 Jul;22:100756.
PMID: 32346617 DOI: 10.1016/j.bbrep.2020.100756

Development of resistance to chemo- and radiotherapy in patients suffering from advanced cervical cancer narrows the therapeutic window for conventional therapies. Previously we reported that a combination of the selective BCL-2 family inhibitors ABT-263 and A-1210477 decreased cell proliferation in C33A, SiHa and CaSki human cervical cancer cell lines. As ABT-263 binds to both BCL-2 and BCL-XL with high affinity, it was unclear whether the synergism of the drug combination was driven either by singly inhibiting BCL-2 or BCL-XL, or inhibition of both. In this present study, we used the BCL-2 selective inhibitor ABT-199 and the BCL-XL selective inhibitor A1331852 to resolve the individual antitumor activities of ABT-263 into BCL-2 and BCL-XL dependent mechanisms. A-1210477 was substituted for the orally bioavailable S63845. Four cervical cancer cell lines were treated with the selective BCL-2 family inhibitors ABT-199, A1331852 and S63845 alone and in combination using 2-dimensional (2D) and 3-dimensional (3D) cell culture models. The SiHa, C33A and CaSki cell lines were resistant to single agent treatment of all three drugs, suggesting that none of the BCL-2 family of proteins mediate survival of the cells in isolation. HeLa cells were resistant to single agent treatment of ABT-199 and A1331852 but were sensitive to S63845 indicating that they depend on MCL-1 for survival. Co-inhibition of BCL-2 and MCL-1 with ABT-199 and S63845, inhibited cell proliferation of all cancer cell lines, except SiHa. However, the effect of the combination was not as pronounced as combination of A1331852 and S63845. Co-inhibition of BCL-XL and MCL-1 with A1331852 and S63845 significantly inhibited cell proliferation of all four cell lines. Similar data were obtained with 3-dimensional spheroid cell culture models generated from two cervical cancer cell lines in vitro. Treatment with a combination of A1331852 and S63845 resulted in inhibition of growth and invasion of the 3D spheroids. Collectively, our data demonstrate that the combination of MCL-1-selective inhibitors with either selective inhibitors of either BCL-XL or BCL-2 may be potentially useful as treatment strategies for the management of cervical cancer.

Matched MeSH terms: Cell Proliferation
Fulltext Cytotoxic Activity of Isoniazid Derivative in Human Breast Cancer Cells

Barathan M, Zulpa AK, Vellasamy KM, Mariappan V, Shivashekaregowda NKH, Ibrahim ZA, et al.

In Vivo, 2021 8 20;35(5):2675-2685.
PMID: 34410956 DOI: 10.21873/invivo.12551

BACKGROUND/AIM: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells.
MATERIALS AND METHODS: Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays.
RESULTS: ITHB4 demonstrated a lower IC50 compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC50, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G2/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death.
CONCLUSION: ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models.

Matched MeSH terms: Cell Proliferation
Fulltext Characterization and Expression of Senescence Marker in Prolonged Passages of Rat Bone Marrow-Derived Mesenchymal Stem Cells

Ridzuan N, Al Abbar A, Yip WK, Maqbool M, Ramasamy R

Stem Cells Int, 2016;2016:8487264.
PMID: 27579045 DOI: 10.1155/2016/8487264

The present study is aimed at optimizing the in vitro culture protocol for generation of rat bone marrow- (BM-) derived mesenchymal stem cells (MSCs) and characterizing the culture-mediated cellular senescence. The initial phase of generation and characterization was conducted using the adherent cells from Sprague Dawley (SD) rat's BM via morphological analysis, growth kinetics, colony forming unit capacity, immunophenotyping, and mesodermal lineage differentiation. Mesenchymal stem cells were successfully generated and characterized as delineated by the expressions of CD90.1, CD44H, CD29, and CD71 and lack of CD11b/c and CD45 markers. Upon induction, rBM-MSCs differentiated into osteocytes and adipocytes and expressed osteocytes and adipocytes genes. However, a decline in cell growth was observed at passage 4 onwards and it was further deciphered through apoptosis, cell cycle, and senescence assays. Despite the enhanced cell viability at later passages (P4-5), the expression of senescence marker, β-galactosidase, was significantly increased at passage 5. Furthermore, the cell cycle analysis has confirmed the in vitro culture-mediated cellular senescence where cells were arrested at the G0/G1 phase of cell cycle. Although the currently optimized protocols had successfully yielded rBM-MSCs, the culture-mediated cellular senescence limits the growth of rBM-MSCs and its potential use in rat-based MSC research.

Matched MeSH terms: Cell Proliferation
Fulltext PCNA Expression In Epithelial Linings Of Odontogenic Cysts

Sudiono, J., Zain, R.B.

Ann Dent, 2003;10(1):-.
MyJurnal

Proliferating Cell Nuclear Antigen (PCNA) is one of the several markers of cellular proliferation. Epithelial proliferations play a significant role in the behaviour of odontogenic lesions. The objective of this study was to describe and compare the distribution of PCNA expression within the epithelial linings of odontogenic cysts. A total of 49 cases of odontogenic cysts consisting of 18 radicular cysts, 16 dentigerous cysts, 15 odontogenic keratocysts (OKCs) was studied. All tissues were processed routinely prior to embedding in paraffin. PCNA immunohistochemical staining was performed on 4 !-tm thick deparaffinized sections mounted on sialinized slides using the peroxidase antiperoxidase method. The distributions of PCNA expression in the cysts linings were noted and comparison was made qualitatively and quantitatively. PCNA labelling index was used for the quantitative assessment. The results showed that PCNA staining was distributed in the basal and supra basal cells for radicular cysts, dentigerous cysts, and OKCs. PCNA labelling index was highest in OKC (22.33±4.07). The high PCNA labelling index in OKC is indicative of high proliferative activity thus supporting previous reports of OKC as the most aggressive type of odontogenic cysts.

Matched MeSH terms: Cell Proliferation
Fulltext Cytotoxicity and oxidative stress evaluation of alginate/cockle shell powder nanobiocomposite bone scaffold on osteoblast

B. Hemabarathy Bharatham, Zariyantey Abdul Hamid, Nurnadiah Ahmad

Jurnal Sains Kesihatan Malaysia, 2017;15(1):97-103.
MyJurnal

Biocompatibility and growth of osteoblast on bone scaffolds play an important role towards their therapeutic application.
The presence of oxidative stress generated by bone scaffolds highly influences osteoblast growth and its functional
performance. In this study in-vitro interaction of developed Alginate/Cockle Shell powder nanobiocomposite bone scaffold
on osteoblast with regards to cytotoxicity and oxidative stress are evaluated. Cytotoxicity studies using MTT assays
revealed a significant increase in viability of cultured osteoblast in the presences of the scaffold extracts. The growth of
osteoblast on the scaffold were not deterred with the presence of any major oxidative stress factors as determined through
oxidative stress profile studies using SOD, GSH and ROS assays. The nanobiocomposite scaffold evaluated in this study
shows promising use in regards to facilitating osteoblast proliferation, growth and viability.

Matched MeSH terms: Cell Proliferation
Fulltext Biocompatibility assessment of fabricated melt-derived 45S5 bioactive glass on dental cells proliferation

Mohd Zain N.S., Tajudin S.S., Mohd Noor S.N.F., Mohamad H.

Journal of Biomedical and Clinical Sciences, 2016;1(1):26-32.
MyJurnal

Thisstudy aim tocharacterize melt-derivedbioactive glass and to determinethe bioactive glass (BG) suitability for dental usagethrough proliferative activity assessment of stem cells from human exfoliated deciduous teeth (SHED)when exposed to bioactive glass conditioned medium. Bioglass 45S5 in mole percentages (46.13% SiO2, 26.91% CaO, 24.35% Na2O and 2.60% P2O5)was synthesizedthrough melt-derived and characterized usingX-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR)to confirm and identify its properties.SHEDwere used to evaluate the biocompatibility of 45S5 by exposing the cells to various concentration of BG-conditioned medium (1-10 mg/ml) using alamarBlue assay. The BG produced has an amorphous structureas shown by XRD analysis. TheSi-O-Si bending, asymmetric Si-O stretching and asymmetricSi-O-Si stretchingbands were observed in the BG structure supporting the presenceof silicate network. For alamarBlue assay, SHED cultured in BG-conditioned medium showed high proliferation rate when subjected to minimal powder content in the DMEM cell culture medium.Hence, it can be concluded that SHED cultured in lower powder content of the BG-conditioned media showedhigh proliferative activity suggesting the potential of the BG for dental usage.

Matched MeSH terms: Cell Proliferation
Fulltext Curcumin: the spicy modulator of breast carcinogenesis

Banik U, Parasuraman S, Adhikary AK, Othman NH

J Exp Clin Cancer Res, 2017 Jul 19;36(1):98.
PMID: 28724427 DOI: 10.1186/s13046-017-0566-5

Worldwide breast cancer is the most common cancer in women. For many years clinicians and the researchers are examining and exploring various therapeutic modalities for breast cancer. Yet the disease has remained unconquered and the quest for cure is still going on. Present-day strategy of breast cancer therapy and prevention is either combination of a number of drugs or a drug that modulates multiple targets. In this regard natural products are now becoming significant options. Curcumin exemplifies a promising natural anticancer agent for this purpose. This review primarily underscores the modulatory effect of curcumin on the cancer hallmarks. The focus is its anticancer effect in the complex pathways of breast carcinogenesis. Curcumin modulates breast carcinogenesis through its effect on cell cycle and proliferation, apoptosis, senescence, cancer spread and angiogenesis. Largely the NFkB, PI3K/Akt/mTOR, MAPK and JAK/STAT are the key signaling pathways involved. The review also highlights the curcumin mediated modulation of tumor microenvironment, cancer immunity, breast cancer stem cells and cancer related miRNAs. Using curcumin as a therapeutic and preventive agent in breast cancer is perplexed by its diverse biological activity, much of which remains inexplicable. The information reviewed here should point toward potential scope of future curcumin research in breast cancer.

Matched MeSH terms: Cell Proliferation

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