Enhanced induction of apoptosis in a radio-resistant bladder tumor cell line by combined treatments with X-rays and wortmannin
Departamento de Biología Celular, Facultad de Biologia, Universidad de Sevilla Avda. Reina Mercedes s/n, 41012 Sevilla, Spain. Biophysik
(Impact Factor: 1.53).
10/2008; 47(4):445-52. DOI: 10.1007/s00411-008-0188-6
The radiosensitizing effect of wortmannin (WM) treatment during and after irradiation was studied in radioresistant bladder tumor cell lines with normal (MGH-U1 cells) or defective p53 activity (RT112 cells). WM modulated G(2)/M cell cycle arrest induced by higher X-ray doses (10 Gy) in both cell lines, although the alteration was significant only in RT112 cells. The observation suggests that WM activity is independent of p53. Constitutive expression of DNA-PKcs was found to be higher in RT112 cells than in MGH-U1. Treatment with WM enhanced radiation-induced apoptosis significantly in RT112 cells while it had no effect on MGH-U1 cells. Although a variety of PI3-kinases and PI3-K like kinases (including ATM) could be inhibited by WM, our observation of increased early lethality by WM treatment in RT112 is in agreement with previous results. They suggest that the WM-dependent radiosensitization of RT112 is a direct consequence of the inhibition of DNA-PK, resulting in the inhibition of DSB repair in the fast component. This early effect in the p53 deficient cell line could also indicate that processes other than apoptosis may contribute to the increased radiosensitization. In our opinion, the expression level of DNA-PKcs in human tumor cells may be a good predictor for the success of DNA-PKcs inhibitors when used as radiosensitizers.
Available from: Xiaodong Liu
- "Additionally, wortmannin combined with X-rays inhibited DNA-dependent protein kinase (DNA-PK), resulting in the inhibition of double-strand break (dsb) repair in the fast component. This effect enhanced the induction of apoptosis during the radiosensitization of bladder tumors (58). Moreover, increased levels of heat shock protein (Hsp) 27 and 70 have been identified to be closely correlated with tumorigenesis, metastasis, resistance to anticancer therapeutics and thus a poor prognosis in a wide range of tumors. "
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ABSTRACT: Traditional Chinese medicine (TCM) has been demonstrated to have potent cytotoxic activity against certain malignant tumors. Ionizing radiation (IR) is one of the most effective methods used in the clinical treatment of cancer. The drawback of a single formula is that it limits the treatment efficacy for cancer, while comprehensive strategies require additional theoretical support. However, a combination of different antitumor treatment modalities is advantageous in restricting the non-specific toxicity often observed with an extremely high dose of a single regimen. The induction of apoptotic cell death is a significant process in tumor cells following radiotherapy or chemotherapy, and resistance to these treatments has been linked to a low propensity for apoptosis. Autophagy is a response of cancer cells to IR or chemotherapy, and involves the prominent formation of autophagic vacuoles in the cytoplasm. In this review, the synergistic effects of TCM and radiotherapy are summarized and the underlying mechanisms are illustrated, providing new therapeutic strategies for cancer.
Oncology letters 05/2013; 5(5):1439-1447. DOI:10.3892/ol.2013.1245 · 1.55 Impact Factor
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Academic Journal of Second Military Medical University 11/2010; 29(11):1217-1220. DOI:10.3724/SP.J.1008.2009.01217
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07/2012; 1(4):493-501. DOI:10.1002/adhm.201200079
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