Recently, we have designed and synthesized a novel quinoxalinhydrazide, SC144, that showed cytotoxicity in a panel of human cancer cell lines. Here, we found that SC144 exhibited anticancer activity in a panel of drugsensitive and drugresistant colon cancer cell lines. To study the molecular anticancer mechanism of SC144, we further found that it arrested cell cycle progression and induced apoptosis in colon cancer cells, which is associated with the decrease in cyclin D1 expression and the activation of the p38/IL24/ Fas pathway. Additionally, in surgical specimens from 202 colorectal patients, Cyclin D1 expression was significantly higher and IL24 expression was significantly lower in cancer tissue than in adjacent normal mucosa, and there was a significant correlation between IL24 level in colorectal cancer tissue and the survival rate of patients after cytoreductive surgery (P = 0.007). This clinical evidence further supports that SC144 is a promising therapeutic agent for colon cancer therapy.
Mechanistic characterization of SC144 in colon cancer
Grande F;GAROFALO, Antonio
2012-01-01
Abstract
Recently, we have designed and synthesized a novel quinoxalinhydrazide, SC144, that showed cytotoxicity in a panel of human cancer cell lines. Here, we found that SC144 exhibited anticancer activity in a panel of drugsensitive and drugresistant colon cancer cell lines. To study the molecular anticancer mechanism of SC144, we further found that it arrested cell cycle progression and induced apoptosis in colon cancer cells, which is associated with the decrease in cyclin D1 expression and the activation of the p38/IL24/ Fas pathway. Additionally, in surgical specimens from 202 colorectal patients, Cyclin D1 expression was significantly higher and IL24 expression was significantly lower in cancer tissue than in adjacent normal mucosa, and there was a significant correlation between IL24 level in colorectal cancer tissue and the survival rate of patients after cytoreductive surgery (P = 0.007). This clinical evidence further supports that SC144 is a promising therapeutic agent for colon cancer therapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.