In this study, we selected 100 nM as an optimal concentration of vincristine which does not effect on the viability of CRC cells using MTT assay. Vincristine induced demethylation of methylated genes in CRC cells to the same extent as 5 aza dC. In addition, vincristine restored the mRNA expression of CHST10, ELOVL4, FLI1, STK33, SOX5, and ZNF304 in CRC cells. Interestingly, the methylation status of AKR1B1 was not affected, but its mRNA expression was increased by both drugs. It may be regulated by upstream genes, with a demethylating effect by both drugs. Our results provide insights into the potential functional impact of vincris tine on methylated genes in CRC. Conclusions This study has identified novel candidate genes, AKR1B1, CHST10, ELOVL4, SOX5, STK33, and ZNF304, and provided evidence for their suitability as methylation bio markers of CRC.

We also analyzed the DNA methylation based therapeutic effects of vincristine in CRC. Background Drugs that interfere with mitosis are part of the most successful cancer chemotherapeutic compounds cur rently used in clinical practice. Development of che motherapeutic drugs that target experienced the mitotic cycle has focused on inhibition of the mitotic spindle through in teractions with microtubules. Drugs targeting micro tubules such as taxanes and vinca alkaloids are effective in a wide variety of cancers, however, the hematopoietic and neurological toxicities as well as development of re sistance to this class of drugs severely limit their long term clinical utility.

Novel anti mitotic agents have been designed to target the mitotic apparatus through selleck chemical non microtubule mitotic mediators such as mitotic ki nases and kinesins. A novel attractive non microtubule target is Highly Expressed in Cancer 1, a component of the kin etochore that regulates the spindle checkpoint. Hec1 is of particular interest because of its association with can cer progression. Hec1 directly interacts with mul tiple kinetochore components including Nuf2, Spc25, Zwint 1, and with mitotic kinases Nek2 and Aurora B and its expression is tightly regulated in both nor mal cells and transformed cells during the cell cycle. Rapidly dividing cells express a high level of Hec1, in contrast to very low to undetectable levels of Hec1 in terminally differentiated cells. Hec1 has been demon strated to overexpress in various human cancers includ ing the brain, liver, breast, lung, cervical, colorectal and gastric cancers. From a mechanistic standpoint, tar geted inhibition of Hec1 by RNAi or by small molecules effectively blocks tumor growth in animal models.