Dimethyl sulfoxide inhibits the expression of early growth-response genes and arrests fibroblasts at quiescence

Srinivas, S. Somanchi; Sironmani, T. Anitha; Shanmugam, G.

doi:10.1016/0014-4827(91)90262-s

Cited by 23 publications

(14 citation statements)

References 34 publications

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“…DMSO treatment lengthened LISP-1 doubling time as described previously for other poorly differentiated colonic cells (15,16), increasing the G0/G1 phase fraction as in other two models, i.e., human leukemia and Chinese hamster ovary (CHO) cells (25,26). The corresponding down-regulation of the c-myc mRNA levels already reported in other cell models (27,28) confirmed that the cell cycle of LISP-1 was arrested in response to DMSO. Changes in S-phase compartments have been previously reported to be associated with changes in different integrins, namely CD11b, α4 and α2 in hematopoietic and fibroblast cell lines (6)(7)(8).…”

Section: Discussionsupporting

confidence: 49%

Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1)

Roela

Brentani

Katayama

et al. 2003

Braz J Med Biol Res

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Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of ß1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO), an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control), as shown by flow cytometry and monoclonal antibodies, expressed α2 (63.8 ± 11.3% positive cells), α3 (93.3 ± 7.0%), α5 (50.4 ± 12.0%) and α6 (34.1 ± 4.9%) integrins but not α1, α4, αv or ß4. Cells adhered well to laminin-1 (73.4 ± 6.0%) and fibronectin (40.0 ± 2.0%) substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that α2, α3 and α6 mediated laminin-1 adhesion, but neither α3 nor α5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 ± 2.4% vs DMSO: 70.7 ± 2.5%) while simultaneously reducing α5 (24.2 ± 19%) and α6 (14.3 ± 10.8%) expression as well as c-myc mRNA (7-fold), the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, α3 and α5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 ± 2 cells vs DMSO: 64 ± 6 cells), was blocked by an antibody against α6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/ migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

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Section: Discussionsupporting

confidence: 49%

Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1)

Roela

Brentani

Katayama

et al. 2003

Braz J Med Biol Res

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“…For instance, DMSO has been shown to inhibit c-myc expression (Darling et al 1989), arrest cell cycle progression thus affecting cell proliferation in different cell types (Srinivas et al 1991). Further DMSO may lead to the collapse of mitochondrial membrane potential, release of cytochrome c from the mitochondria and activation of caspase-9 and caspase-3 (Liu et al 2001).…”

Section: Discussionmentioning

confidence: 98%

Diverse effects of dimethyl sulfoxide (DMSO) on the differentiation potential of human embryonic stem cells

Pal

Mamidi²,

Das³

et al. 2011

Arch Toxicol

173

126

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In vitro disease modeling using pluripotent stem cells can be a fast track screening tool for toxicological testing of candidate drug molecules. Dimethyl sulfoxide (DMSO) is one of the most commonly used solvents in drug screening. In the present investigation, we exposed 14- to 21-day-old embryoid bodies (EBs) to three different concentrations of DMSO [0.01% (low dose), 0.1% (medium dose) and 1.0% (high dose)] to identify the safest dose that could effectively be used as solvent. We found that DMSO treatment substantially altered the morphology and attachment of cells in concurrence with a significant reduction in cell viability in a dose-dependent manner. Gene expression studies revealed a selective downregulation of key markers associated with stemness (Oct-4, Sox-2, Nanog and Rex-1); ectoderm (Nestin, TuJ1, NEFH and Keratin-15); mesoderm (HAND-1, MEF-2C, GATA-4 and cardiac-actin); and endoderm (SOX-17, HNF-3β, GATA-6 and albumin), indicating an aberrant and untimely differentiation trajectory. Furthermore, immunocytochemistry, flow cytometry and histological analyses demonstrated substantial decrease in the levels of albumin and CK-18 proteins coupled with a massive reduction in the number of cells positive for PAS staining, implicating reduced deposits of glycogen. Our study advocates for the first time that DMSO exposure not only affects the phenotypic characteristics but also induces significant alteration in gene expression, protein content and functionality of the differentiated hepatic cells. Overall, our experiments warrant that hESC-based assays can provide timely alerts about the outcome of widespread applications of DMSO as drug solvent, cryoprotectant and differentiating agent.

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“…Dimethyl sulfoxide (DMSO) is a well-known differentiation inducer and has been shown to induce an efficient and reversible G1 phase arrest in CHO cells (Fiore et al 2002), human lymphoid cell lines (Sawai et al 1990) and mouse fibroblasts (Srinivas et al 1991). DMSO-induced growth arrest is associated with restored contact inhibition of cell growth and prevention of densitydependent-apoptosis (Fiore and Degrassi 1999).…”

Section: (Ii) Cell Engineering Based Approachesmentioning

confidence: 99%

Proliferation control strategies to improve productivity and survival during CHO based production culture

2007

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Chinese Hamster Ovary cells are the primary system for the production of recombinant proteins for therapeutic use. Protein productivity is directly proportional to viable biomass, viability and culture longevity of the producer cells and a number of approaches have been taken to optimise these parameters. Cell cycle arrest, particularly in G1 phase, typically using reduced temperature cultivation and nutritional control have been used to enhance productivity in production cultures by prolonging the production phase, but the mechanism by which these approaches work is still not fully understood. In this article, we analyse the public literature on proliferation control approaches as they apply to production cell lines with particular reference to what is known about the mechanisms behind each approach.

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Dimethyl sulfoxide inhibits the expression of early growth-response genes and arrests fibroblasts at quiescence

Cited by 23 publications

References 34 publications

Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1)

Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1)

Diverse effects of dimethyl sulfoxide (DMSO) on the differentiation potential of human embryonic stem cells

Proliferation control strategies to improve productivity and survival during CHO based production culture

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