Open Access Highly Accessed Research article

Starvation-induced activation of ATM/Chk2/p53 signaling sensitizes cancer cells to cisplatin

Yandong Shi1*, Emanuela Felley-Bosco1*, Thomas M Marti1, Katrin Orlowski2, Martin Pruschy2 and Rolf A Stahel1

Author Affiliations

1 Laboratory of Molecular Oncology, Zürich, Switzerland

2 Department of Radiation Oncology, University Hospital Zürich, University of Zürich, Zürich, Switzerland

For all author emails, please log on.

BMC Cancer 2012, 12:571  doi:10.1186/1471-2407-12-571

Published: 4 December 2012

Additional files

Additional file 1:

Figure S1. Serum starvation and CDDP both activate ATM in ZL55 cancer cells and when combined result in an enhanced activation of the ATM. Anti-phosphoATM-Ser1981 (pATM) immuno-staining of untreated ZL55 cells (A) and those treated with 8 μM CDDP alone (B), serum starvation alone (C), or both together (D) are shown. In (A-D), images of anti-pATM staining (in red) are in left, and images of DAPI staining in middle while on the right are the overlap. “S” in (C) and (D) stands for serum starvation. Figure S2. p53 is knockout in HCT116p53−/−cells. No p53 was detected in the protein extract from CDDP-treated HCT116p53−/− cells while it was induced in p53-proficient HCT116 cells. β-Actin was used as loading control. Figure S3. STS with water ad libitum is tolerable for animals. Animals regained most of the lost body weight during the next day after starvation. Figure S4. Serum starvation protects normal cells from CDDP cytotoxity. MTT assays were performed after primary normal cell cultures LP9, SDM104 and SDM85, which was established from a normal pleural tissue received from a patient undergoing cancer unrelated thoracic surgery (this study was approved by the Zurich University Hospital ethic committee and a written informed consent was obtained from the patient), were treated with CDDP alone, serum starvation alone or both together (* for P<0.002; ** for P<3.0x10-5). CDDP8 and CDDP20 stands for 8 μM and 20 μM CDDP, respectively. Figure S5. Serum starvation suppressed the CDDP-induced activation of ATM in normal cells. Anti-phosphoATM-Ser1981 (pATM) immuno-staining of untreated SDM104 cells (A) and those treated with 8 μM CDDP alone (B), serum starvation alone (C), or both together (D) are shown. In (A-D), images of anti-pATM staining (in red) are in left, and images of DAPI staining in middle while on the right are the overlap. “S” in (C) and (D) stands for serum starvation. Figure S6. Serum starvation does not induce the expression of oxidative stress marker, HO-1 in ZL55 and A549 cancer cells. Western blot results with antibodies against HO-1 for protein extracts from untreated control and those treated with CDDP alone, serum starvation alone, or both together are shown for ZL55 (A) and A549 (B) cells. β-Actin was used as loading control.

Format: PDF Size: 347KB Download file

This file can be viewed with: Adobe Acrobat Reader

Open Data