Rana M. El-Tabakh

Conference 2024 Live Talk

Talk Title

Adding colchicine to doxorubicin for better anti-tumor efficacy and less toxicity in an in vivo cancer model; a step toward their use clinically

Authors and Affiliations

Rana M. El-Tabakh1, Eman F. Wasfey1, Sophie Van Linthout2, Nadia M. Hamdy1,3,
Mohamed L. Salem4,5

1. Biochemistry department, Faculty of Pharmacy, Ain Shams University, Abassia, 11566, Cairo, Egypt
2. Berlin Institute of Health (BIH) at Charité – Universitätmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany
3. National Committee of Medicines, Academy of Scientific Research and Technology (ASRT), Al Kasr Al Aini, Ministry of Higher Education, Cairo 11694, Egypt
4. Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt
5. Center of Excellence in Cancer Research, New Tanta University Teaching Hospital, Tanta, University, Tanta, Egypt

Abstract

Background

Although doxorubicin (DOX) is an effective chemotherapeutic drug, it induces serious adverse effects, toxicity and resistance. This study aims to evaluate whether the anti-inflammatory drug colchicine (COL) can reduce DOX side effects and enhance its anti-tumor efficacy, allowing the use of lower doses.

Methods

To fulfill our aim, we used Ehrlich ascitic carcinoma (EAC)-bearing CD1 mice and treated them with high and low doses of DOX (DOXhigh and DOXlow) in the presence or absence of COL. Mice were inoculated intraperitoneally with 0.25 × 106 EAC-cells/mouse and then treated with DOXhigh (2 mg/kg), DOXlow (1 mg/kg), COL (5 µmol/kg), DOXhigh/COL and DOXlow/COL. On day 8 of tumor inoculation, 50% of the mice were sacrificed to evaluate tumor volume, total tumor cell count, EAC cell apoptosis, cell cycle, hematological, and biochemical parameters, including liver and kidney functions, oxidative stress (OS) markers, C-reactive protein (CRP), and interleukin 1-beta (IL-1β). The remaining 50% of mice were left to determine groups survival.

Results

Combination therapy of COL with DOXhigh or DOXlow enhanced the overall antitumor effect of DOX as evidenced by an enhancement in tumor parameters, an increase in EAC cell apoptosis, and induction of cell cycle arrest at the G2M phase. Additionally, their co-treatment mitigated DOX adverse effects as evidenced by an improvement in the measured markers. Moreover, animals’ survival was extended.

Conclusions

This study opens a new avenue to colchicine use with doxorubicin in the clinical setting and registering a patent for this combination. Instead of synthesizing new anti-cancer molecules, we can use this combination. This way, we can enhance the antitumor efficacy of toxic anticancer drugs with less side effects, less toxicity, and lower doses. This study is part of a project in collaboration with Germany through the Egypt-German program funded by the Science and Technology Development Fund (STDF) in Egypt.