Dose dependent role of Emodin and BTB14431 in suspension colon cancer model in rats

Background. An “In Silico 2D/3D Conformer Screening” for structural similar antitumor substances to Curcumin was carried out and the novel antrachinone BTB14431 was found. Emodin, contained in several Chinese medical plants and BTB14431 are known to be potential inhibitors of the COP9-signalosome - stabilizing the tumor suppressor protein p53. The aim of this study was to analyze the suppressing effects on colorectal cancer in a standardized rat model (WAG/Rij). Methods. A suspension of CC531 colon cancer cells was applied to the cecum after laparotomy and, additionally, at the back of animals. Therapy was conducted twice daily for 7 days, with increasing doses of BTB14431, Emodin and with isotone sodium chloride solution (control) intravenously (iv) or intraperitoneally (ip). Therapy was initiated the day of tumor cell application. Peripheral blood samples were taken before surgery and on day 7. 21 days after the end of therapy, the animals were euthanized and tumor growth was evaluated. Results. Data showed a downward trend of the total tumor growth after iv and ip treatment with low doses of BTB14431 and Emodin. Differential blood analysis showed apoptosis, but no major changes in hemogram. Increasing doses of Emodin elevated total mortality rate exponentially. Conclusions.Although apoptosis was verified, no significant tumor suppressing effects could be observed for iv and ip treatment of both agents in our model. This stays in contrast to former in vitro studies. Agents remain viable novel substances. They will be the subject of upcoming studies. Additional data is needed to evaluate the significance of the “In Silico Screening” to identify potential in vivo anti-tumor drugs.