Transforming growth factor beta‐1 enhances cytotoxic effect of doxorubicin in human lung adenocarcinoma cells of A549 line

Abstract

Transforming growth factor beta-1 (TGFbeta-1) is a regulator of cell proliferation, differentiation and apoptosis. Doxorubicin (adriamycin), an anthracycline drug causing double-strand DNA breaks, is widely used in anticancer chemotherapy. Here we demonstrated that TGFbeta-1 enhanced cytotoxic (proapoptotic) action of doxorubicin towards cultured human lung carcinoma A549 cells. Western-blot analysis and immunocytochemistry were used to show that doxorubicin induced PARP degradation in A549 cells, and TGFbeta-1 enhanced that action of the drug. The obtained results suggest a possibility of biomodulating effect of TGFbeta-1 on tumor cell treatment with doxorubicin.

Features of senescence and cell death induced by doxorubicin in A549 cells: organization and level of selected cytoskeletal proteins

“…Indeed, as the TUNEL results indicated, mostly cells with G 2 /M DNA content and polyploid cells were affected by DNA double-or single-strand breaks at the highest dose of the drug. Previous studies have similarly documented rather low efficiency of cell death induction in the population of doxorubicin-treated A549 cells (He et al 2005;Crescenzi et al 2005;Filyak et al 2007). Recently, a stem cell subpopulation has been isolated from A549 cell line, displaying significantly lower Annexin V staining than the remaining cells in the presence of doxorubicin and as such probably contributing to resistance to this drug (Sung et al 2008).…”

“…This antineoplastic antibiotic acts mainly by intercalation into the DNA molecule and disruption of DNA and RNA synthesis, as well as by inhibiting of the DNA topoizomerase II and producing DNA single-and double-strand breaks (Meriwether and Bachur 1972;Binaschi et al 1997). Some features of senescence and cell death were described in human lung adenocarcinoma A549 cells after treatment with doxorubicin (Crescenzi et al 2005;Klein et al 2005;Filyak et al 2007). Here, we describe organization and level of vimentin and nuclear G-actin in A549 cell line after treatment with doxorubicin (Adriblastin), on the background of selected markers of senescence and cell death.…”

TGF-β in the Bone Microenvironment: Role in Breast Cancer Metastases

“…For example, targeting TGF-β signaling can enhance the therapeutic efficacy of various cytotoxic agents as was recently shown for rapamycin [170] and doxorubicin [171,172]. Unpublished studies in our laboratory show that SD-208 dosed in combination with an inhibitor of bone resorption, zoledronic acid, reduces the progression of established osteolytic metastases from breast cancer more effectively than either therapy alone [173].…”

EW-7197, a Novel ALK-5 Kinase Inhibitor, Potently Inhibits Breast to Lung Metastasis

“…The TGFbRI/II kinase inhibitor, LY-2109761, in combination with temozolomide and radiotherapy in a glioblastoma model was shown to inhibit tumor growth compared with controls (25). Furthermore, loss of TGFb signaling can increase the therapeutic efficacy of cancer treatment with rapamycin (34) and doxorubicin (35). In the 4T1 mouse model, a combination of ixabepilone, capecitabine, and 1D11 treatment reduces primary tumor growth and metastasis (36), and this combinatorial treatment has also shown some efficacy for patients with breast cancer resistant to anthracycline and taxane therapy (36).…”