Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
2251-9645
10
3
2021
8
1
Curcumin in Combination with Other Adjunct Therapies for Brain Tumor Treatment:
Existing Knowledge and Blueprint for Future Research
163
180
EN
Kavita
Peter
Department of Biotechnology, Barkatullah University, Bhopal, M.P, India.
kavitaniraj07@gmail.com
N
0000-0002-0564-8450
Santosh Kumar
Kar
Nano Herb Research Lab, KIIT-TBI, Bhubaneshwar, Odisha, India.
santoshkariis@rediffmail.com
N
0000-0001-5089-6245
Ragini
Gothalwal
Department of Biotechnology, Barkatullah University, Bhopal, M.P, India.
ragini_gothalwal@yahoo.com
N
0000-0002-2781-3488
Puneet
Gandhi
Department of Research, Bhopal Memorial Hospital and Research Centre, Bhopal, M.P, India.
puneetgandhi67@yahoo.com
Y
0000-0001-9690-5207
10.22088/IJMCM.BUMS.10.3.163
Malignant brain tumors proliferate aggressively and have a debilitating outcome. Surgery followed by chemo-radiotherapy has been the standard procedure of care since 2005 but issues of therapeutic toxicity and relapse still remain unaddressed. Repurposing of drugs to develop novel combinations that can augment existing treatment regimens for brain tumors is the need of the hour. Herein, we discuss studies documenting the use of curcumin as an adjuvant to conventional and alternative therapies for brain tumors. Comprehensive analysis of data suggests that curcumin together with available therapies can generate a synergistic action achieved through multiple molecular targeting, which results in simultaneous inhibition of tumor growth, and reduced treatment-induced toxicity as well as resistance. The review also highlights approaches to increase bioavailability and bioaccumulation of drugs when co-delivered with curcumin using nano-cargos. Despite substantial preclinical work on radio-chemo sensitizing effects of curcumin, to date, there is only a single clinical report on brain tumors. Based on available lab evidence, it is proposed that antibody-conjugated nano-curcumin in combination with sub-toxic doses of conventional or repurposed therapeutics should be designed and tested in clinical studies. This will increase tumor targeting, the bioavailability of the drug combination, reduce therapy resistance, and tumor recurrence through modulation of aberrant signaling cascades; thus improving clinical outcomes in brain malignancies.
Glioblastoma, polyphenol, combination therapy, resistance, sensitization, synergistic
http://ijmcmed.org/article-1-1702-en.html
http://ijmcmed.org/article-1-1702-en.pdf
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
2251-9645
10
3
2021
8
1
Role of mTOR Complex 1 Signaling Pathway in the Pathogenesis of Diabetes Complications; A Mini Review
181
188
EN
Amir
Yarahmadi
Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
amir20_d2011@yahoo.com
N
0000-0001-9397-6608
Negar
Azarpira
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
negarazarpira@gmail.com
N
0000-0002-5549-0057
Zohreh
Mostafavi-Pour
Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
zmostafavipour88@yahoo.co.uk
Y
0000-0002-3779-177X
10.22088/IJMCM.BUMS.10.3.181
The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine-protein kinase that senses and combines various environmental signals to regulate the growth and homeostasis of human cells. This signaling pathway synchronizes many critical cellular processes and is involved in an increasing number of pathological conditions such as diabetes, cancer, obesity, and metabolic syndrome. Here, we review different complications of diabetes that are associated with mTOR complex 1 imbalance. We further discuss pharmacological approaches to treat diabetes complications linked to mTOR deregulation.
Diabetes, complications, mTOR, mTOR complex 1, signaling
http://ijmcmed.org/article-1-1707-en.html
http://ijmcmed.org/article-1-1707-en.pdf
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
2251-9645
10
3
2021
8
1
Evaluation of FOXCUT, CCAT2, and HULC LncRNA Expression Levels and Apoptosis Induction by Sodium Butyrate in PC-3 and LNCAP Prostate Cancer Cell Lines
189
199
EN
Sanaz
Kavoosi
Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
San.kavousi.sci@iauctb.ac.ir
N
0000-0002-5865-8433
Seyed Ataollah
Sadat Shandiz
Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
Ata.sadatshandiz@iauctb.ac.ir
Y
0000-0002-5053-0507
Nastaran
Asghari Moghaddam
Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
nas.asgharimoghaddam@iauctb.ac.ir
N
0000-0002-6553-7875
10.22088/IJMCM.BUMS.10.3.189
Sodium butyrate (NaBu) is a short-chain fatty acid acting as a histone deacetylase inhibitor, and has been shown to be a potential regulator of cancer cell death. This study aimed to evaluate the effect of NaBu on cell cycle control, apoptosis, and expression of some lncRNAs in two human prostate cancer cells (PC-3 and LNCAP). Cell viability was assessed and the appropriate dose was determined using the MTT assay. Real-time PCR technique was also used to evaluate the expression levels of HULC, FOXCUT, and CCAT2 lncRNAs. Apoptosis was diagnosed using annexin V staining, and cell cycle distribution was then assessed using flow cytometry with propidium iodide DNA staining. NaBu induced apoptosis in both prostate cancer cell lines in a dose-dependent manner. The expressions of CCAT2 and HULC lncRNAs genes have significantly decreased in the presence of NaBu (P <0.05) in both PC3 and LNCAP cell lines, in comparison with the control. However, no significant difference was observed in the expression of FOXCUT lncRNAs. Moreover, the results of flow cytometry showed an increase in cell cycle arrest of LNCAP cell line at the sub-G1 stage as compared to the control cells, but no significant difference was observed between the control cells and NaBu-exposed PC-3 cells. In addition, the percentages of early and late apoptotic cells following treatment with NaBu were 80% and 49.63% in LNCAP and PC-3 cells, respectively. Our results suggest that NaBu has a positive effect on the induction of apoptosis and inhibition of cell cycle in PC-3 and LNCAP prostate cancer cells.
Prostatic neoplasms, RNA, long noncoding RNA, apoptosis
http://ijmcmed.org/article-1-1623-en.html
http://ijmcmed.org/article-1-1623-en.pdf
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
2251-9645
10
3
2021
8
1
Metformin is a Novel Suppressor for Vimentin in Human Gastric Cancer Cell Line
200
206
EN
Shiva
Valaee
Research Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
shiva.valaee@gmail.com
N
0000-0003-4350-448X
Mehdi
Shamsara
Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
shamsa@nigeb.ac.ir
N
0000-0003-1119-5758
Mohammad Mehdi
Yaghoobi
Research Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
m.yaghoobi@kgut.ac.ir
Y
0000-0003-1434-6224
10.22088/IJMCM.BUMS.10.3.200
Vimentin, an intermediate filament of mesenchymal cells, is upregulated in epithelial-mesenchymal transition (EMT) and has a main role in cancer metastasis. As a new strategy to control metastatic outgrowth, EMT markers are generally inhibited using some drugs or specific siRNA. In this study, AGS gastric cancer cells were treated with metformin and vimentin-specific siRNA (vim-siRNA) for 48 h. The impact of metformin and vim-siRNA on vimentin downregulation in AGS cells were analyzed by quantitative PCR and Western blot. Following treatment with metformin and vim-siRNA, cell motility, migration and invasion abilities of AGS cells were also analyzed. The results showed that inhibition of vimentin due to metformin was comparable with the vim-siRNA. Furthermore, wound-healing and invasion assays showed a significant decrease in migration and invasion of AGS cells following metformin and vim-siRNA treatment. Our finding for the first time indicated that metformin can be an alternative to specific siRNA for inhibition of vimentin expression and migration of AGS cell line. Taken together, our data indicates that the use of metformin might have a priority to siRNA for inhibition of gastric cancer cell behaviors siRNA is more unstable and expensive than metformin, and needs special vehicles and delivery strategies for efficient transfection of cells. Further in vivo studies can reveal metformin's potential in inhibition of EMT and metastasis of cancer cells.
Gastric cancer, metformin, vimentin, epithelial-mesenchymal transition
http://ijmcmed.org/article-1-1552-en.html
http://ijmcmed.org/article-1-1552-en.pdf
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
2251-9645
10
3
2021
8
1
Quercetin Arrests in G2 phase, Upregulates INXS LncRNA and Downregulates UCA1 LncRNA in MCF-7 Cells
207
217
EN
Fatemeh
Rezaie
Department of Biology, Zarghan Branch, Islamic Azad University, Zarghan, Iran.
sara.re3731@gmail.com
N
0000-0002-9833-7095
Mohammad Javad
Mokhtari
Department of Biology, Zarghan Branch, Islamic Azad University, Zarghan, Iran.
Mj.mokhtari@gmail.com
Y
0000-0001-5066-9632
Mehdi
Kalani
Department of Immunology, Prof. Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
mkalani2008@gmail.com
N
0000-0002-7091-6466
10.22088/IJMCM.BUMS.10.3.207
One of the most prevalent malignancies, which have severe effects on women's health, is breast cancer. Quercetin, a flavonoid found in vegetables, tea, and fruits, is known to have bioactive properties, such as anti-inflammatory, anti-oxidant, as well as anti-cancer. Long non-coding RNAs (lncRNAs) have been recognized to function as primary regulators of diverse cellular processes, including differentiation, development, and cell fate. INXS and UCA1 are lncRNAs that are upregulated and downregulated, respectively in cancer cells. This research aimed to assess the impact of quercetin on the expression of INXS and UCA1 genes in MCF-7 cells. Various quercetin concentrations at different times were used to treat MCF-7 cells. The cell viability and IC50 values were determined using MTT assay. Then, MCF-7 cells were incubated with various quercetin concentrations for 24, 48, and 72 h. Cell cycle analyzes were evaluated by flow cytometry. The levels of INXS and UCA1 genes expression compared with the GAPDH gene at different concentrations of quercetin were quantified using real-time PCR method. Based on the results, quercetin exerted a dose- and time-dependent inhibitory impact on the viability of MCF-7 cells. Furthermore, quercetin induced cell cycle arrest at the G2 phase in MCF-7 cells. Also, quercetin induced INXS upregulation and UCA1 downregulation in the MCF-7 cell line. These data suggest that quercetin might increase cell death by upregulating INXS and downregulating UCA1 lncRNAs in MCF-7 cells.
Breast cancer, quercetin, MCF-7 cells, INXS, UCA1
http://ijmcmed.org/article-1-1540-en.html
http://ijmcmed.org/article-1-1540-en.pdf
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
2251-9645
10
3
2021
8
1
Oral Contraceptive Steroids Promote Papillary Thyroid Cancer Metastasis by Targeting Angiogenesis and Epithelial-Mesenchymal Transition
218
226
EN
Mohammad Hossein
Dehghan
Biochemistry Department, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
mohammad.dehghan9@gmail.com
N
0000-0002-1292-2673
Mohammad Reza
Ashrafi
Department of Biochemistry, Afzalipoor Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
M.Ashraafi@gmail.com
N
0000-0002-0499-6090
Mehdi
Hedayati
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
hedayati47@gmail.com
N
0000-0001-5816-775X
Setareh
Shivaee
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Setareh.shivaee@gmail.com
N
0000-0002-0668-9852
Sadegh
Rajabi
Traditional Medicine and Materia Medica Research Center (TMRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sadegh.rajabi2017@gmail.com
Y
0000-0001-7027-4881
10.22088/IJMCM.BUMS.10.3.218
Thyroid cancer is the most prevalent type of endocrine malignancy with the highest incidence rate among women under 45 years old. Ethinylestradiol (EE) and levonorgestrel (LNG) are two steroid components of low-dose oral contraceptives used all over the world. In this study, we aimed to examine the possible effects of the combination of these two steroids on metastasis and angiogenic factors in BCPAP papillary thyroid cancer (PTC) cell line. After treatment of BCPAP cells with the combination of 20 nM EE and 90 nM LNG, mRNA expression levels of long noncoding RNAs HOTAIR and MALAT1, angiogenic and antiangiogenic gene markers VEGFA and THBS1, and epithelial-mesenchymal transition (EMT) biomarkers CDH1, CDH2, FN1, and VIM were analyzed by real-time PCR. Additionally, the protein expression of VEGFA was semiquantified by Western blotting. Results showed that the combination of LNG and EE significantly elevated the level of VEGFA protein and mRNA expression of VEGFA, MALAT1, HOTAIR, CDH2, FN1, and VIM genes while decreased CDH1 gene expression but had no marked effect on the expression of THBS1 gene in comparison with the control group. Also, our results suggest that LNG and EE may increase the metastatic and migratory properties of BCPAP cells via modulating angiogenic and EMT biomarkers. These data may highlight the potential of exogenous steroids in the advancement of PTC tumors.
Papillary thyroid cancer, metastasis, migration, angiogenesis, epithelial-mesenchymal transition
http://ijmcmed.org/article-1-1650-en.html
http://ijmcmed.org/article-1-1650-en.pdf
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
2251-9645
10
3
2021
8
1
Identification of Novel Insertions and Deletions in Haematopoietic Stem/Progenitor Cells in de novo Myelodysplastic Syndromes
227
233
EN
Manoj
Bandara
Department of Pre-Clinical Sciences, Faculty of Medicine, General Sir John Kotelawala Defence University, Rathmalana, Sri Lanka.
hemali@anat.cmb.ac.lk
N
0000-0003-0118-8757
Hemali
Goonasekera
Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.
bandarawmms@kdu.ac.lk
N
0000-0001-8623-1640
Vajira
Dissanayake
Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.
vajira@anat.cmb.ac.lk
Y
0000-0002-3264-6856
10.22088/IJMCM.BUMS.10.3.227
Myelodysplastic Syndromes (MDS) are clonal haematological stem cell disorders. The molecular basis of MDS is heterogeneous and the molecular mechanisms underlying biology of this complex disorder are not fully understood. Genetic variations (GVs) occur in about 90% of patients with MDS. It has been shown that in addition to the single nucleotide variations, insertions and deletions (indels) in the key genes that are known to drive MDS, could also play a role in pathogenesis of MDS. However, only a few genetic studies have analyzed indels in MDS. The present study reports indels of bone marrow (BM) derived CD34+ haematopoietic stem/progenitor cells of 20 newly diagnosed de novo MDS patients using next generation sequencing.A total of 88 indels (9 insertions and 79 deletions) across 28 genes were observed. The genes that showed more than five indels are BCOR (N=6), RAD21 (N=6), TP53 (N=8), ASXL1 (N=9), TET2 (N=9) and BCORL1 (N=10). Deletion in the BCORL1 gene (c.3957_3959delGGA, TGAG>TGAG/T) was the most recurrent deletion and was observed in 4/20 patients. The other recurrent deletions reported were EZH2 (W15X, N=2) and RAD21 (G274X, N=3). The recurrent insertions were detected in the FLT3 (E598DYVDFREYE, N=3) and in the NPM1 (L287LCX, N=3) genes. The findings of this study may have a diagnostic, prognostic and a therapeutic value for MDS after validation using a larger cohort.
Insertions and deletions, myelodysplastic syndromes, haematopoietic stem and progenitor cells, next generation sequencing
http://ijmcmed.org/article-1-1720-en.html
http://ijmcmed.org/article-1-1720-en.pdf