Low-dose fractionated radiation potentiates the effects of paclitaxel in wild-type and mutant p53 head and neck tumor cell lines

Swatee Dey, Paul M. Spring, Suzanne Arnold, Joseph Valentino, Damodaran Chendil, William F. Regine, Mohammed Mohiuddin, Mansoor M. Ahmed

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


This study was designed to: (a) evaluate the induction of hyper-radiation sensitivity (HRS), a phenomenon observed at low doses of radiation (<1 Gy); (b) compare the potentiating effects of single dose radiation (2 Gy) versus the effect of low-dose fractionated radiation (LDFRT; <1 Gy) on Paclitaxel; and (c) understand the molecular mechanism of LDFRT-mediated chemo-potentiating effects, in wild-type p53 SCC-61 and p53 mutant SQ-20B head and neck squamous; cell carcinoma cell lines. Both cell lines exhibited the HRS phenomenon at low radiation doses. Compared with SCC-61 cells, SQ-20B cells were resistant to radiation and Paclitaxel alone. A significant enhancement of radiation sensitization by Paclitaxel (0.5 or 1 nM) was observed in both cell lines. Chemo-potentiation of Paclitaxel by single 2-Gy radiation was observed in SCC-61 cells but not in SQ-20B cells. However, LDFRT (0.5 Gy in four fractions) significantly chemo-potentiated the effect of Paclitaxel in both cell lines. The cell cycle regulator p53 and its target genes p21waf1/cip1 and BAX were induced in SCC-61 cells treated with 2 Gy, Paclitaxel, or in combination, but not in SQ-20B cells. These treatments elevated the antiapoptotic BCL-2 protein in SQ-20B cells but not in SCC-61 cells. Interestingly, LDFRT treatment in both cell lines with or without Paclitaxel down-regulated nuclear factor κ B activity and BCL-2 protein expression and simultaneously up-regulated BAX protein. These findings strongly suggest that LDFRT (at these doses, HRS phenomenon is observed) can be used in combination with Paclitaxel to overcome the antiapoptotic effects of BCL-2 and nuclear factor κ B.

Original languageEnglish
Pages (from-to)1557-1565
Number of pages9
JournalClinical Cancer Research
Issue number4
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • General Medicine


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