Effects of concomitant use of THC and irinotecan on tumour growth and biochemical markers in a syngeneic mouse model of colon cancer

Sep 24, 2026

Uploaded by Adam

Clinical use of irinotecan is frequently limited by adverse effects that reduce patient quality of life, while publicly supported Δ9-tetrahydrocannabinol (THC) products may be taken without clear evidence of anticancer benefit. This study evaluates combined IRI and THC in a syngeneic colorectal cancer mouse model. CT26 tumor-bearing BALB/c mice received IRI with or without THC for 7 days, and responses were assessed via tumor growth, organ weights, cholinesterase activity, and oxidative stress. Irinotecan toxicity included weight loss and increased oxidative stress; concomitant THC reduced IRI efficacy in suppressing tumor growth, warranting further molecular and distribution studies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Introduction

Rationale and background

Materials and Methods

Chemicals and reagents

Experimental design

198 Žunec S, et al. Effects of concomitant use of THC and irinotecan on tumour growth and biochemical markers in a syngeneic mouse model of colon cancer Arh Hig Rada Toksikol 2023;74:198-206 Original article DOI: 10.2478/aiht-2023-74-3765 Effects of concomitant use of THC and irinotecan on tumour growth and biochemical markers in a syngeneic mouse model of colon cancer Suzana Žunec1, Irena Brčić Karačonji1, Martin Čatalinac2, Andreja Jurič1, Anja Katić1, Goran Kozina3, Vedran Micek1, Marijana Neuberg3, and Ana Lucić Vrdoljak1 1 Institute for Medical Research and Occupational Health, Zagreb, Croatia 2 University of Zagreb Faculty of Science, Zagreb, Croatia 3 University North, University Centre Varaždin, Varaždin, Croatia [Received in July 2023; Similarity Check in July 2023; Accepted in September 2023] Clinical treatment with the antineoplastic drug irinotecan (IRI) is often hindered by side effects that significantly reduce the quality of life of treated patients. Due to the growing public support for products with Δ9-tetrahydrocannabinol (THC), even though relevant scientific literature does not provide clear evidence of their high antitumour potential, some cancer patients take unregistered preparations containing up to 80 % THC. This study was conducted on a syngeneic colorectal cancer mouse model to test the efficiency and safety of concomitant treatment with IRI and THC. Male BALB/c mice subcutaneously injected with CT26 cells were receiving 60 mg/kg of IRI intraperitoneallyon day 1 and 5 of treatment and/or 7 mg/kg of THC by gavage a day for 7 days. Treatment responses were evaluated based on changes in body, brain, and liver weight, tumour growth, blood cholinesterase activity, and oxidative stress parameters. Irinotecan’s systemic toxicity was evidenced by weight loss and high oxidative stress. The important finding of this study is that combining THC with IRI diminishes IRI efficiency in inhibiting tumour growth. However, further studies, focused on more subtle molecular methods in tumour tissue and analytical analysis of IRI and THC distribution in tumour-bearing mice, are needed to prove our observations. KEY WORDS: antitumour activity; cannabinoid-based preparations; oxidative stress; systemic toxicity Cannabinoids, the active compounds of the cannabis plant, have become popular alternative medicine, especially in alleviating the adverse effects of cancer treatment such as pain and nausea (1) . However, they can cause side effects and interact with the metabolism of other drugs, antineoplastic drugs with a narrow therapeutic window in particular. One such drug is irinotecan [ 7-e t h y l-1 0- ( 4- ( 1-pi pe r i d i no) -1-pi pe r i d i no) carbonyloxycamptothecin] (IRI), indicated to treat metastatic colorectal cancer and different solid tumours (2) . The antitumor activity of IRI is often associated with clinically important side effects like the acute cholinergic syndrome, myelosuppression, and late-onset diarrhoea (3), so it often happens that cancer patients instead of taking conventional supportive therapy resort to cannabis products in order to alleviate the side effects of chemotherapy (4) . Although there are preparations with purified or synthetic cannabinoids approved for medical use, many patients decide to buy cannabis products on the illegal market (5) . Considering that illegal preparations may contain very high levels (>80 %) of the main psychoactive cannabis component Δ9-tetrahydrocannabinol (THC) (6), this can diminish the therapeutic efficiency of the antineoplastic drug or cause unacceptable toxicities. Corresponding author: Suzana Žunec, Institute for Medical Research and Occupational Health, Toxicology Unit, Ksaverska cesta 2, 10000 Zagreb, Croatia; E-mail: [suzana@imi.hr](suzana@imi.hr), ORCID: 0000-0002-7710-8250 We already know that the metabolic pathways of IRI and THC overlap in the first two phases of metabolic biotransformation, regulated by the enzymes from

FAQs

What problem does the study address regarding irinotecan treatment?

Irinotecan treatment is often hindered by side effects that significantly reduce patients’ quality of life.

How was THC administered in the mouse model?

Male BALB/c mice with CT26 tumors received THC at 7 mg/kg by gavage for 7 days, with or without irinotecan.

What was the key finding about combining THC with irinotecan?

Concomitant THC diminished irinotecan’s efficiency in inhibiting tumor growth, despite irinotecan showing systemic toxicity markers such as weight loss and elevated oxidative stress.

Sep 24, 2026

Uploaded by Adam