Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Tarantula cubensis alcohol extract enhances the tumoricidal effect of capecitabine via multiple pathways in azoxymethane-induced colorectal cancer in rats

Gokhan Akcakavak¹ , Zeynep Celik², Ozhan Karatas³, Osman Dogan², Ozgur Ozdemir², Mehmet Tuzcu²

¹Department of Pathology, Faculty of Veterinary Medicine, Aksaray University, Merkez/AKSARAY, Turkey; ²Department of Pathology, Faculty of Veterinary Medicine, Selcuk University, Selcuklu/KONYA, Turkey; ³Department of Pathology, Faculty of Veterinary Medicine, Sivas Cumhuriyet University, Merkez/S?VAS, Turkey.

For correspondence:- Gokhan Akcakavak Email: gokhan.akcakavak@aksaray.edu.tr Tel:+905549977046

Accepted: 2 February 2024 Published: 29 February 2024

Citation: Akcakavak G, Celik Z, Karatas O, Dogan O, Ozdemir O, Tuzcu M. Tarantula cubensis alcohol extract enhances the tumoricidal effect of capecitabine via multiple pathways in azoxymethane-induced colorectal cancer in rats. Trop J Pharm Res 2024; 23(2):291-297 doi: 10.4314/tjpr.v23i2.8

© 2024 The authors.
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Abstract

Purpose: To evaluate the effect of a combination of alcohol extract of Tarantula cubensis (TCAE) and capecitabine (CAP) in the treatment of azoxymethane (AOM)-induced colorectal cancer (CRC).

Methods: Forty-two Wistar albino rats were divided into 7 groups with 6 rats in each group. The groups consisted of Control (C), Control+TCAE (C-TCAE), Control+CAP (C-CAP), Cancer control (CC), Cancer+TCAE (CC-TCAE), Cancer+CAP (CC-CAP) and Cancer+CAP+TCAE (CC-CAP+TCAE). To induce CRC, AOM (15 mg/kg) was administered to rats subcutaneously (sc) twice at a one-week interval to all the groups except control. After the 15th week, TCAE (0.2 mL/rat sc) was administered to CC-TCAE group every 3 days for 4 weeks, and CAP (40 mg/kg/day) was administered by gavage to CC-CAP group for 4 weeks. In CC-CAP+TCAE group, TCAE (0.2 mL/rat sc) was administered every 3 days for 4 weeks, and CAP (40 mg/kg/day) was administered gavage for 4 weeks. Animals were treated for 19 weeks. Aberrant crypt foci (ACF) were evaluated histopathologically among CC, CC-TCAE, CC-CAP, and CC-CAP+TCAE groups. β-catenin, CD15, Proliferating Cell Nuclear Antigen (PCNA), and Nuclear Factor kappa B (NF-κB) expression levels were immunohistochemically compared among all groups.

Results: Histopathologically, ACF scores were significantly increased in CC group, while a significant decrease in the relevant scores (p < 0.001) was observed in CC-CAP and CC-CAP+TCAE treatment groups, and the lowest scores were in CC-CAP+TCAE group. Immunohistochemically, in CC group, β-catenin, Nuclear Factor kappa B (NF-κB), Proliferating Cell Nuclear Antigen (PCNA) and CD15 expressions were highly irregular. CC-CAP and CC-CAP+TCAE groups had significantly reduced expressions (p < 0.001), and the lowest expressions were in CC-CAP+TCAE group.

Conclusion: The combined use of TCAE and CAP in treatment of CRC has a synergistic effect and increases the anticancer efficacy of TCAE, and CAP. More studies at the molecular level are needed in the future to demonstrate the clinical benefit of TCAE supplementation during the treatment of CRC with CAP.

Keywords: Colorectal cancer, Azoxymethane, ?-catenin, NF-?B, PCNA, CD15