In vitro efficacy of a novel chemoradiopotentiator--taxoltere metro.
OBJECTIVE
To evaluate the in vitro cytotoxic and radiopotentiating effects of a novel paclitaxel analog (taxoltere metro) on Chinese hamster ovary (CHO) cells and human colon cancer cells.


METHODS
Three cell lines (CHO cells, HCT116 human colon carcinoma cells [paclitaxel-sensitive], and VM46 cells [paclitaxel-resistant subline of HCT116]) were employed in this study. Cell survival was determined using the standard colony-forming assay. The ID50 value (drug concentrations required to reduce colony formation to 50% of the control value) was determined as a cytotoxic index from each cell survival curve. The sensitizer enhancement ratio (SER) as a radiopotentiating endpoint was determined as the ratio of the D0 values (with or without drugs) under hypoxic or air conditions.


RESULTS
Taxoltere metro was 5-15 times more effective in killing CHO cells than paclitaxel under both hypoxic and euoxic treatment conditions. Cytocidal effects of taxoltere metro on HCT116 cells and VM46 cells were 28 and 70 times higher than those of paclitaxel (p<0.001), respectively. Taxoltere metro also produced significant radiopotentiating effects on euoxic CHO and HCT116 cells, but not on hypoxic cells. The SER value of taxoltere metro for CHO cells was about 2.3 at a dose of 100 nM. With HCT116 cells, taxoltere metro yielded an SER of 1.2 at the low dose of 10 nM. In contrast, the parent compound paclitaxel yielded little or no radiosensitization with either CHO or HCT116 cells.


CONCLUSIONS
The results demonstrate that taxoltere metro is significantly more potent than paclitaxel in chemoradiopotentiating CHO cells and HCT116 human colon carcinoma cells. The data strongly suggest that taxoltere metro could be a promising chemoradiopotentiating agent for treatment of cancer.
Yang
L X
LX
Department of Radiation Oncology, St. Mary's Medical Center, San Francisco, CA 94117, USA. Yang@cooper.cpmc.org
Wang
H J
HJ
Holton
R A
RA
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000633:toxicity; D016466:CHO Cells; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D006224:Cricetinae; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000633:toxicity; D043823:Taxoids; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel