Transforming growth factor‐β1 enhances the lethal effects of DNA‐damaging agents in a human lung‐cancer cell line

Abstract

In tissue culture conditions, exogeneous active transforming growth factor-b1 (TGF-b1) enhances the lethal effect of DNA-damaging agents (UV-C, gamma rays, cisplatin, methotrexate and 5-fluorouracil) toward human A549 cells and mink Mv1Lu cells, as detected by the loss of their capacity to give rise to colonies; both these cell lines harbor a wild-type p53, as determined by immunoprecipitation. Contrastingly, the sole effect of the cytokine used alone is to inhibit reversibly the multiplication of the same cells without further impairing, once withdrawn from their environment, their capacity to divide and give rise to colonies. The lethal synergy between TGF-b1 and UV-C was studied on mink and human cell lines, and the biomodulation by TGF-b1 of cell killing by cisplatin, gamma rays, 5-fluorouracil or methotrexate was tested only on human cells. As investigated with UV-Cirradiated human A549 cells, TGF-b1 appears to enhance apoptosis rather than to disturb the repair of DNA photolesions (mainly pyrimidine dimers) by the nucleotidic excision repair pathway according to results of nucleosomal ladder and comet tests. Our data raise the possibility that, in vivo, TGF-b1 might affect the curative and/or undesirable secondary side effects of cancer therapy. Int.

Scanning electron microscopy with an ionic liquid reveals the loss of mitotic protrusions of cells during the epithelial–mesenchymal transition

“…The number of PCNA‐positive cells increased in control cells compared with the cells before treatment with TGF‐β1 (A549 was 3.64% ± 3.63% and Panc‐1 was 9.28% ± 9.88%, respectively); however, we did not detect a significant difference between the control and TGF‐β1‐treated cells. The lower average percentage of PCNA‐positive cells among the TGF‐β1‐treated cells may indicate suppression of cell cycle progression in TGF‐β1‐treated cells, as reported earlier (Gibbs et al,2009; Raynal et al,1997). Based on these results, we concluded that TGF‐β1 did not affect the viability of A549 and Panc‐1 cells.…”

“…The loss of filopodia may be mediated by abnormal formation/disassembly of actin filament structures because TGF‐β1 can cause actin filament production, but this awaits further study. However, growth suppression by TGF‐β1 may be a candidate mechanism as described in other studies (Gibbs et al,2009; Raynal et al,1997). In fact, in our preliminary experiment, mitotic arrest due to colcemide treatment also decreased the number of filopodia (data not shown).…”

Growth arrest in G1 protects against oxygen‐induced DNA damage and cell death

“…Because TGF‐β1 can alter anti‐oxidant enzyme expression (Arsalane et al, 1997), it remains possible that the protective effects of TGF‐β1 were not due solely to growth arrest in G1. We were also concerned that further studies with TGF‐β1 may be problematic because it has been shown to directly affect cell viability as well as enhance the lethal effects of genotoxins (Sanchez et al, 1996; Raynal et al, 1997; data not shown). For these reasons, we examined whether serum deprivation, which also elicits a G1 arrest due to failure to activate G1 cyclin d ‐dependent kinase, altered survival during hyperoxia.…”

Genome‐wide screening of loci associated with drug resistance to 5‐fluorouracil‐based drugs

“…( 32 ) TGFβ1 is a 25‐kDa polypeptide that is involved in the regulation of many tissues, cells and organ functions, and enhances the lethal effect of DNA‐damaging agents including 5‐FU. ( 33 ) The TGFβ1/bone morphogenetic protein signaling pathway is not only required for cytokine signaling, but may also be an important factor for 5‐FU‐mediated apoptosis. ( 34 ) Midkine ( MDK ), located on chromosome 11p11.2, is a heparin‐binding growth factor that has been associated with the development of cancer, ( 35 ) and was consistently overexpressed in 5‐FU‐resistant cells compared with their parent cells.…”