Anti-tumorigenic Effects of Emodin and Its’ Homologue BTB14431 on Vascularized Colonic Cancer in a Rat Model

Document Type: Research Articles

Authors

1 Department of General and Visceral Surgery, Division of Molecular and Clinical Research St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.

2 Private veterinary practice of Maria Freiburger, Lehesten, Germany

3 Clinic for Minimal Invasive Surgery (MIC), Berlin, Germany

4 School of Pharmaceutical Sciences, Xiamen University, Xiang’an South Road, Xiamen 361102, China.

5 Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.

Abstract

Objective: New drugs for cancer treatment are being sought worldwide. Therapeutic agents derived from natural substances can provide cost-efficient options. We evaluated the effect of emodin, an active natural anthraquinone derivate, and it’s in-silico homologue the novel substance BTB14431 in vivo. Method: CC-531 colon cancer cells were implanted intraperitoneal (ip) and subcutaneous (sc) in 100 WAG/Rij rats. 28 days after tumor cell implantation, solid cancers were treated for 7 days by varying doses of BTB14431 (0.3 mg/kg body weight; 1.7 mg/kg) or emodin (2.5 mg/kg; 5 mg/kg). Treatment was applied either via an intravenous (iv) port catheter or by ip injection. Saline solution served as control. 21 days after final dose all animals were euthanized and ip tumor weight, sc tumor weight and animal body weight (bw) were determined by autopsy. Significant lower total tumor weight occurred after iv treatment with low dose BTB14431 (6.8 g; 90% confidence interval (CI) 5.3 - 8.2 g; p ≤ 0.01) and also low and high concentrations of emodin (9.4 g; CI 7.9 - 10.7 g; p ≤ 0.01 and 8.3 g; CI 7.6 - 9.3; p ≤ 0.01). Iv treatment by high dose BTB14431 did not lead to a decline in tumor weight. High dose ip treatment by emodin led to a lower overall (11.1 g; CI 10.1 – 13.8 g; p ≤ 0.01) and ip tumor weight (8.6 g; CI 6 – 10.4 g; p ≤ 0.01). Sc tumor weight was not affected. All other ip treatments did not result in changes of combined, ip or sc tumor weight. Bw decreased during iv treatment in all animals and increased after treatment was completed. Regain of bw was stronger in animals receiving low dose emodin. Conclusion: Our study shows promising anti-cancer properties of BTB14431 and supports the evidence regarding emodin as a natural antitumorigenic agent. Optimal dosing of iv emodin and especially BTB 14431 for maximal efficacy remains unclear and should be a subject of further research. 
 

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