Elimination of Colon Cancer Stem-Like Cells by the Combination of Curcumin and FOLFOX

5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics but with limited success. This could partly be due to the enrichment of cancer stem cells (CSCs) that are resistant to conventional chemotherapy. Therefore, validation of a nontoxic agent that can either cause reversal of chemoresistance or promote the killing of CSCs would be highly desirable. The current study examines whether curcumin, the major active ingredient of turmeric, either alone or together with FOLFOX, would be an effective strategy to eliminate colon CSCs. Exposure of colon cancer HCT-116 or HT-29 cells to FOLFOX that inhibited their growth led to the enrichment of CSC phenotype as evidenced by increased proportion of CD133-, CD44-, and/or CD166-positive cells and epidermal growth factor receptor (EGFR) levels. Treatment of FOLFOX-surviving colon cancer cells with either curcumin alone or together with FOLFOX resulted in a marked reduction in CSCs, as evidenced by the decreased expression of CD44 and CD166 as well as EGFR and by their ability to form anchorage-dependent colonies. They also caused disintegration of colonospheres. Increased expression of EGFR in FOLFOX-surviving cells could be attributed to hypomethylation of the EGFR promoter, whereas an opposite phenomenon was observed when the FOLFOX-surviving cells were treated with curcumin and/or FOLFOX. These changes were accompanied by parallel alterations in the levels of DNA methyltransferase 1. In conclusion, our data suggest that curcumin by itself or together with the conventional chemotherapeutic could be an effective treatment strategy for preventing the emergence of chemoresistant colon cancer cells by reducing/eliminating CSCs.     

Charge trapping by solitions—A possible transport mechanism in macromolecular systems

Macromolecules and their aggregates possess polar modes which, when excited, cause deformations, which provoke in turn elastic restoring forces. Even the simplest of such models (involving polarization and elastic modes along a chain) admit localized excitations (solitons) endowed with a characteristic degree of stability; and these provide a mechanism for charge trapping which may be of importance in the understanding of the elusively high efficiency of charge transfer over macroscopic distances evidently involved in various biomolecular processes.     

The phytochemistry of the annonaceae

Both alkaloidal and non-alkaloidal compounds so farsolated from Annonaceous plants are reviewed. 319 secondary products have been reported from 150 spe