Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer

Abstract

The anticancer effect of a new pyrazole derivative, KI-10F (2-(4-(2-(4-(dimethylamino) phenyl)pyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol‑1-yl) acetonitrile)•3.5HCl) was evaluated in human colon cancer cells. KI-10F strongly suppressed the growth of human colon cancer cells and induced apoptosis by increasing the proportion of sub-G1 presenting apoptotic cells as well as causing cell cycle arrest at the G2/M phase. Apoptosis by KI-10F was confirmed by observation of an increase in the expression of cleaved caspase-3, caspase-8, caspase-9 and Bax, and the decrease of Bcl-2. Decreased expression of HIF-1α and VEGF, and the inhibition of HUVEC tube formation and migration showed that KI-10F effectively inhibited the angiogenesis process. Furthermore, in vivo study in a mouse xenograft model showed that KI-10F produced a stronger antitumor activity than 5-FU, a conventional anticancer drug prescribed for the treatment of colon cancer. The effects of KI-10F on tumor proliferation (PCNA), angiogenesis (CD34) and apoptosis (cleaved caspase-3) were evaluated by immunohistochemistry using isolated tumor tissue samples. Taken together, our results demonstrated that KI-10F induces apoptosis and inhibits cell growth and angiogenesis both in vitro and in vivo. We suggest that KI-10F is an effective chemotherapeutic candidate for use against colon cancer.

Pyrazoles as potential anti-angiogenesis agents: a contemporary overview

“…A novel pyrazole derivative KI-10F [2-(4-(2-(4-(Dimethyl-amino)phenyl)pyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl), structure in Figure 1] acetonitrile was developed and evaluated in human colon cancer cells (Hong et al, 2012). Its synthesis is not described (only the formation of the HCl salt) into the paper however the specific compound inhibited angiogenesis both in vivo and in vitro , categorizing it as a chemotherapeutic candidate.…”

Tissue factor-targeted lidamycin inhibits growth and metastasis of colon carcinoma

“…The primary treatment of colon cancer is to surgically remove part of or the whole of the colon. Chemotherapy is an important supplementary approach that is capable of prolonging survival for individuals whose cancer has spread to other organs (1,2). Targeted chemotherapy specifically kills tumor cells with minimal toxicity to normal cells.…”