Journal
NEOPLASIA
Volume 11, Issue 9, Pages 901-909Publisher
ELSEVIER SCIENCE INC
DOI: 10.1593/neo.09594
Keywords
-
Categories
Funding
- VA Biomedical Laboratory Research and Development Service Merit Review Program
- American Heart Association [0830287N]
- National Institutes of Health (NIH) [P50 CA103130-01, HL-52490]
- NIH
- Cancer Center Support (University of Texas MD Anderson Cancer Center) [CA16672]
- Charitable Leadership Foundation (Clifton Park, NY)
- NIH/National Cancer Institute [5RO1 CA89827]
Ask authors/readers for more resources
At present, there is no efficient curative therapy for cancer patients with advanced metastatic disease. Targeting of antiapoptotic molecules acting on the mitochondrial apoptosis pathway could potentially augment antimetastatic effect of cytotoxic drugs. Similarly to Bcl-2 family members, beta-galactoside-binding lectin galectin-3 protects cancer cells from apoptosis induced by cytotoxic drugs through the mitochondrial pathway. In this study, we tested the hypothesis that inhibiting galectin-3 antiapoptotic function using a synthetic low-molecular weight carbohydrate-based compound lactulosyl-L-leucine (Lac-L-Leu) will augment apoptosis induced in human cancer cells by paclitaxel and increase its efficacy against established metastases. Treatment with synthetic glycoamine Lac-L-Leu alone reduced the number of established MDA-MB-435Lung2 pulmonary metastases 5.5-fold (P = .032) but did not significantly affect the incidence of metastasis. Treatment with paclitaxel alone (10 mg/kg three times with 3-day intervals) had no significant effect on the incidence or on the number of MDA-MB-435Lung2 metastases. Treatment with Lac-L-Leu/ paclitaxel combination decreased both the number (P = .02) and the incidence (P = .001)of pulmonary metastases, causing a five-fold increase in the number of metastasisfree animals from 14% in the control group to 70% in the combination therapy group. The median number of lung metastases dropped to 0 in the combination therapy group compared with 11 in the control (P = .02). Synergistic inhibition of clonogenic survival and induction of apoptosis in metastatic cells by Lac-L-Leu/paclitaxel combination was functionally linked with an increase in mitochondrial damage and was sufficient for the antimetastatic activity that caused a reversal and eradication of advanced metastatic disease in 56% of experimental animals.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available