1.Breast Cancer Selective Disruption of Actin Cytoskeleton by Diallyl Trisulfide
Eun-Ryeong HAHM ; Sivapar V. MATHAN ; Rana P. SINGH ; Shivendra V. SINGH
Journal of Cancer Prevention 2022;27(2):101-111
Diallyl trisulfide (DATS) is an attractive anti-cancer phytochemical with in vitro and in vivo growth inhibitory effects against different solid tumors including breast cancer. We have shown previously that an immortalized mammary epithelial cell line (MCF-10A) is resistant to growth inhibition by DATS. In this study, we performed RNA-seq analysis using a breast cancer cell line (SK-BR-3) and MCF-10A cells to gain insights into cancer selective effects of DATS. The Gene Ontology analysis revealed upregulation of genes associated with actin cytoskeleton but downregulation of mitochondria-related genes in the SK-BR-3 human breast cancer cell line but not in the non-oncogenic MCF-10A cell line upon treatment with DATS. Quantitative real-time reverse transcription polymerase chain reaction confirmed DATS-mediated upregulation of several actin cytoskeleton-related genes in the SK-BR-3 cell line. The DATS treatment dose-dependently disrupted actin cytoskeleton in the SK-BR-3 cell line, whereas the MCF-10A cell line was more resistant to this effect. The DATS treatment caused a marked increase in phosphorylation of dynamin-1-like (DRP1) protein in the SK-BR-3 cell line. However, the DATS-mediated apoptosis was not affected by genetic deletion of DRP1 protein. The Reactome pathway analysis showed downregulation of genes associated with citric acid cycle in the SK-BR-3 cell line but not in the MCF-10A cells. However, expression of aconitase 2 or dihydrolipoamide S-succinyltransferase was not affected by DATS treatment. In conclusion, this study reveals that actin cytoskeleton is a novel target of DATS in the SK-BR-3 cell line, which may explain its inhibitory effect on breast cancer cell migration.
2.Antifungal Activity of Chaerophylline and Berberine Hydroxide Isolated from Corydalis Species.
Leepika TULI ; R N JHA ; V B PANDEY ; U P SINGH
Mycobiology 2001;29(2):100-103
Chaerophylline and berberine hydroxide, both being alkaloids, isolated from Corydalis chaerophylla and C. longipes respectively were assayed against spore germination of some fungi, e.g. Alternaria solani, A. brassicola, A. brassicicola, Helminthosporium penniseti, Helminthosporium sp., Heterosporium sp., Curvularia penniseti, C. maculens and C. palliscens. While chaerophylline inhibited spore germination of most of the fungi at 1000 ppm, being also effective at 50, 100, 200 and 500 ppm, berberine hydroxide was significantly effective at much lower concentration, i.e., 400 ppm against several fungi. This compound was also effective against some fungi at 50, 100, 150, 200 ppm. There was 100% inhibition of spore germination in several fungi at highest concentration of both the compounds. Some of the fungi showed similar results even at lower concentrations.
Alkaloids
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Alternaria
;
Berberine*
;
Corydalis*
;
Fungi
;
Germination
;
Helminthosporium
;
Spores
3.Effect of Ent-norsecurinine, an Alkaloid, on Spore Germination of Some Fungi.
Mitul GOEL ; S MAURYA ; V B PANDEY ; V P SINGH ; A K SINGH ; U P SINGH
Mycobiology 2002;30(4):225-227
The inhibitory activity of ent-norsecurinine alkaloid was evaluated against spore germination of some plant pathogenic fungi (Curvularia maculans, Curvularia species, C. palliscens, Colletotrichum gloeosporioides, Colletotrichum species, Alternaria solani, A. brassicae, Fusarium udum, Helminthosporium echinoclova and H. penniseti). It inhibited spore germination of all the test fungi. C. maculans, C. species, and C. palliscens were the most sensitive as complete inhibition of spore germination was observed at 1000 ppm. A. solani was not inhibited by this chemical.
Alternaria
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Brassica
;
Colletotrichum
;
Fungi*
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Fusarium
;
Germination*
;
Helminthosporium
;
Plants
;
Spores*
4.Antifungal Activity of Nor-securinine Against Some Phytopathogenic Fungi.
Sangita SAHNI ; S MAURYA ; U P SINGH ; A K SINGH ; V P SINGH ; V B PANDEY
Mycobiology 2005;33(2):97-103
Crude extracts and active principles from medicinal plants have shown potential role in controlling plant diseases in glasshouses as well as in fields as one of the safest and ecofriendly methods. The effect of nor-securinine (an alkaloid) isolated from Phyllanthus amarus has been seen against spore germination of some fungi (Alternaria brassicae, A. solani, Curvularia pennisetti, Curvularia sp., Erysiphe pisi, Helminthosporium frumentacei) as well as pea powdery mildew (Erysiphe pisi) under glasshouse conditions. The sensitivity of fungi to nor-securinine varied considerably. Nor-securinine was effective against most of the fungi. H. frumentacei was more sensitive even at the lowest concentration (1,000 microg/ml). Likewise conidia of E. pisi were also inhibited in partially or completely appressorium formation. Pre-inoculation treatment showed greater efficacy than post-inoculation in inhibiting powdery mildew development on pea plants in a glasshouse. Maximum inhibition occurred at 2000 microg/ml
Brassica
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Complex Mixtures
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Fungi*
;
Germination
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Helminthosporium
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Peas
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Phyllanthus
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Plant Diseases
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Plants, Medicinal
;
Spores
;
Spores, Fungal
5.Diallyl Trisulfide Inhibits Leptin-induced OncogenicSignaling in Human Breast Cancer Cells but Fails toPrevent Chemically-induced Luminal-type Cancer in Rats
Su-Hyeong KIM ; Eun-Ryeong HAHM ; Krishna B. SINGH ; Shivendra V. SINGH
Journal of Cancer Prevention 2020;25(1):1-12
Previous studies have demonstrated inhibitory effect of garlic component diallyl trisulfide (DATS) on growth of breast cancer cellsin vitro and in vivo. This study investigated the effect of DATS on oncogenic signaling regulated by leptin, which plays an importantrole in breast carcinogenesis. Leptin-induced phosphorylation and nuclear translocation of STAT3 was inhibited significantly in thepresence of DATS in MCF-7 (a luminal-type human breast cancer cell line) and MDA-MB-231 (a basal-like human breast cancer cellline). Leptin-stimulated cell proliferation, clonogenic cell survival, and migration and/or invasion ability in MCF-7 and/or MDA-MB-231cells were also suppressed by DATS treatment. DATS exposure resulted in inhibition of leptin-stimulated expression of protein and/or mRNA levels of Bcl-2, Bcl-xL, Cyclin D1, vascular endothelial growth factor, and matrix metalloproteinase-2. Western blotting revealeda decrease in protein levels of phosphorylated STAT3 in breast cancer xenografts from DATS-treated mice when comparedto controls in vivo. However, the incidence of N-methyl-N-nitrosourea-induced luminal-type breast cancer development in rats wasnot affected by oral administration of 5 mg/kg or 25 mg/kg DATS. The present study reveals that oncogenic signaling induced byleptin is inhibited in the presence of DATS but higher doses of this phytochemical may be required to achieve chemopreventive activity.
6.Mechanistic Targets of Diallyl Trisulfide in Human Breast Cancer Cells Identified by RNA-seq Analysis
Eun-Ryeong HAHM ; Su-Hyeong KIM ; Sivapar V. MATHAN ; Rana P. SINGH ; Shivendra V. SINGH
Journal of Cancer Prevention 2021;26(2):128-136
Diallyl trisulfide (DATS), a metabolic by-product of processed garlic, is highly effective in inhibiting growth of human breast cancer cells in vitro and in vivo, but the underlying mechanisms are still not fully understood. In this study, we performed RNA-seq analyses using luminal-type (MCF-7) and basal-like (MDA-MB-231) human breast cancer cells to identify mechanistic targets of DATS. The Reactome Pathway Analysis revealed upregulation of genes associated with SLIT/ROBO tumor suppressor signaling following DATS treatment in both MCF-7 and MDA-MB-231 cells. However, the expression of SLIT2 and ROBO1 proteins or their downstream target C-X-C motif chemokine receptor 4 was not affected by DATS treatment in both cell lines. The Reactome as well as the Gene Ontology Pathways Analyses of the RNA-seq data from DATS-treated cells indicated downregulation of genes associated with G2 /M phase cell cycle arrest in comparison with vehicle-treated control cells. Consistent with the RNA-seq data, DATS treatment caused a significant increase in the fraction of the G2 /M population in both cell lines when compared to corresponding control cells. In addition, Ser10 phosphorylation of histone H3, a mitotic marker, was also increased significantly following DATS treatment in MCF-7 and MDA-MB-231 cells. These results indicate that while SLIT/ROBO signaling is not affected by DATS treatment, cell cycle arrest likely contributes to the antitumor effect of this phytochemical.
7.Mechanistic Targets of Diallyl Trisulfide in Human Breast Cancer Cells Identified by RNA-seq Analysis
Eun-Ryeong HAHM ; Su-Hyeong KIM ; Sivapar V. MATHAN ; Rana P. SINGH ; Shivendra V. SINGH
Journal of Cancer Prevention 2021;26(2):128-136
Diallyl trisulfide (DATS), a metabolic by-product of processed garlic, is highly effective in inhibiting growth of human breast cancer cells in vitro and in vivo, but the underlying mechanisms are still not fully understood. In this study, we performed RNA-seq analyses using luminal-type (MCF-7) and basal-like (MDA-MB-231) human breast cancer cells to identify mechanistic targets of DATS. The Reactome Pathway Analysis revealed upregulation of genes associated with SLIT/ROBO tumor suppressor signaling following DATS treatment in both MCF-7 and MDA-MB-231 cells. However, the expression of SLIT2 and ROBO1 proteins or their downstream target C-X-C motif chemokine receptor 4 was not affected by DATS treatment in both cell lines. The Reactome as well as the Gene Ontology Pathways Analyses of the RNA-seq data from DATS-treated cells indicated downregulation of genes associated with G2 /M phase cell cycle arrest in comparison with vehicle-treated control cells. Consistent with the RNA-seq data, DATS treatment caused a significant increase in the fraction of the G2 /M population in both cell lines when compared to corresponding control cells. In addition, Ser10 phosphorylation of histone H3, a mitotic marker, was also increased significantly following DATS treatment in MCF-7 and MDA-MB-231 cells. These results indicate that while SLIT/ROBO signaling is not affected by DATS treatment, cell cycle arrest likely contributes to the antitumor effect of this phytochemical.
8.Chopstick splinter: A rare cause of bilateral frozen orbits
Bin Lieh O. ; Ong Lee C. ; Tet Min C. ; Raja Selva V. ; Liza-Sharmini AT ; Balaravi P. ; Singh Gurdeep M.
Philippine Journal of Ophthalmology 2006;31(1):42-43
OBJECTIVE: To report an unusual case of frozen orbit caused by an unsuspected intraorbital foreign body.
METHOD: This is a case report.
RESULTS: A 31-year old Chinese man presented with a 6-month history of painless progressive right caruncular growth with mucoid discharge. He also had bilateral progressive reduction in ocular movements. His best-corrected vision was 6/9 bilaterally. A conjunctival granuloma arising from the right caruncle and extending to the cornea and associate with ophthalmoplegia was also present. Orbital computed tomography showed a dense rod-like structure traversing the nasal area, extending from the superomedial wall of the right orbit to the apex of the left orbit with surrounding inflammatory reaction but sparing the optic nerve. The intraorbital foreign body, a 6 cm chopstick splinter, was successfully removed via right lateral rhinotomy.
CONCLUSION: Intraorbital foreign bodies are not uncommonly seen and, generally, the diagnosis is straightforward. Nevertheless, diagnosis, could be missed if it is not suspected.
Human
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Male
;
Adult
;
WOUNDS AND INJURIES
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EYE FOREIGN BODIES
;
EYE DISEASES
;
9.Assessment of thickness of in vivo autograft tendons around the knee and its correlation with anthropometric data, thickness of patella and anterior cruciate ligament tibial foot print diameter
Balgovind S RAJA ; Kshitij GUPTA ; Abdusamad V ; Sukhmin SINGH ; Subhajit MAJI
Anatomy & Cell Biology 2021;54(1):18-24
Inadequate diameters of the autograft tendons are known to be a major cause of graft failure in ligament reconstruction. The purpose of the study was to measure the in-vivo thickness of the available autograft options around the knee and to seek a correlation between the thickness of the tendons and the anthropometric data, patellar thickness and anterior cruciate ligament (ACL) footprint sagittal diameter. Magnetic resonance imaging of 104 consecutive patients with suspected knee injuries were utilized for measurement of the in vivo thickness of pes anserinus tendon (diameter and cross-sectional area [CSA]), patellar tendon (PT) and quadriceps tendon (QT). Pearson’s coefficient was used to find out the relationship between the tendon thickness and anthropometric data, thickness of patella and ACL tibial foot print sagittal diameter. The mean diameters and CSA of the semitendinosus tendon (ST) and gracilis tendon (GT) were 3.77±0.49 mm, 11.62±1.62 mm2 and 2.87±0.27 mm, 6.64±1.18 mm2 respectively. QT and PT thicknesses were 7.36±0.87 mm and 4.50±0.62 mm respectively. Height and the patellar thickness were seen to have moderate correlation with ST and PT thickness. Weak correlation was seen between the other anthropometric variables and tendon thickness. Magnetic resonance imaging (MRI) assessment of tendon sizes is a reliable method with good inter and intra-rater agreement. Assessment of these anatomical structures with help of MRI would be helpful in preoperative planning and can help in identifying those patients at risk of having smaller tendons.
10.Assessment of thickness of in vivo autograft tendons around the knee and its correlation with anthropometric data, thickness of patella and anterior cruciate ligament tibial foot print diameter
Balgovind S RAJA ; Kshitij GUPTA ; Abdusamad V ; Sukhmin SINGH ; Subhajit MAJI
Anatomy & Cell Biology 2021;54(1):18-24
Inadequate diameters of the autograft tendons are known to be a major cause of graft failure in ligament reconstruction. The purpose of the study was to measure the in-vivo thickness of the available autograft options around the knee and to seek a correlation between the thickness of the tendons and the anthropometric data, patellar thickness and anterior cruciate ligament (ACL) footprint sagittal diameter. Magnetic resonance imaging of 104 consecutive patients with suspected knee injuries were utilized for measurement of the in vivo thickness of pes anserinus tendon (diameter and cross-sectional area [CSA]), patellar tendon (PT) and quadriceps tendon (QT). Pearson’s coefficient was used to find out the relationship between the tendon thickness and anthropometric data, thickness of patella and ACL tibial foot print sagittal diameter. The mean diameters and CSA of the semitendinosus tendon (ST) and gracilis tendon (GT) were 3.77±0.49 mm, 11.62±1.62 mm2 and 2.87±0.27 mm, 6.64±1.18 mm2 respectively. QT and PT thicknesses were 7.36±0.87 mm and 4.50±0.62 mm respectively. Height and the patellar thickness were seen to have moderate correlation with ST and PT thickness. Weak correlation was seen between the other anthropometric variables and tendon thickness. Magnetic resonance imaging (MRI) assessment of tendon sizes is a reliable method with good inter and intra-rater agreement. Assessment of these anatomical structures with help of MRI would be helpful in preoperative planning and can help in identifying those patients at risk of having smaller tendons.