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Cedrus libani tar prompts reactive oxygen species toxicity and DNA damage in colon cancer cells

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Abstract

Background

Many chemotherapeutic drugs used in cancer treatment have anticancer properties by inducing reactive oxygen species (ROS). However, the same effect occurs in normal cells, limiting the availability of these drugs. Therefore, studies on the detection of new herbal anticancer agents that have selective effects on cancer cells are of great importance. The aim of this study is to investigate the metabolite profile of Cedrus libani tar and its mechanism of anticancer effect on colon cancer cells.

Methods and results

Effect of cedar tar on cells (12 cancers and 5 normal cell lines) viability was determined by MTT, apoptosis induction was determined by Annexin-V, ROS and MMP determined by flow cytometry assay. Cleaved caspase-8, 9 and Ɣ-H2AX expression determined by western blot. Apoptotic and antioxidant genes expression level determined by qPCR. Metabolite profiling was performed with LC–MS/MS and GC–MS. Cedar tar showed the highest cytotoxic effect among cancer cells in colon cancer (HCT-116, IC50: 30.4 μg/mL) and its toxic effect on normal cells (HUVEC, IC50: 74.07 μg/mL) was less than cancer cell. Cedar tar increases ROS production in colon cancer cells. The metabolite profile of the cedar tar contains high amounts of metabolites such as fatty acids mainly (Duprezianene, Himachalene and Chamigrene), phenolic compounds (mostly Coumarin, p-coumaric acid, Vanillic acid and tr-Ferulic acid etc.) and organic acids (mainly 3-oh propanoic acid, 2-oh butyric acid and 3-oh isovaleric acid etc.).

Conclusion

As a result, it has been found that cedar tar has the potential to be used in the treatment of colon cancer.

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Data availability

The data that support the findings of this study are available from the corresponding author, [IK.], upon reasonable request.

Code availability

Not applicable.

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The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Authors and Affiliations

  1. Medical Promotion and Marketing Program, Health Services Vocational School, Harran University, Şanlıurfa, Turkey

    Ebru Temiz

  2. Department of Medicinal Biochemistry, Medical Faculty, Harran University, Şanlıurfa, Turkey

    Kadir Eği, Ismail Koyuncu, Ozgür Yüksekdag, Murat Tiken & Sükrü Akmese

  3. Department of Molecular Biology and Genetic, Science Faculty, Harran University, Şanlıurfa, Turkey

    Yusuf Kurt

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  1. Ebru Temiz
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  2. Kadir Eği
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  3. Ismail Koyuncu
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  4. Ozgür Yüksekdag
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  5. Yusuf Kurt
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Contributions

ET, IK, KE, and OY, conducted the experiments and contriubuted to data interpretation; ET, MT, OY, SA and YK participated in data analysis, discussion and manuscript preparation and all were involved in manuscript editing.

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Correspondence to Ismail Koyuncu.

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Temiz, E., Eği, K., Koyuncu, I. et al. Cedrus libani tar prompts reactive oxygen species toxicity and DNA damage in colon cancer cells. Mol Biol Rep 49, 7939–7952 (2022). https://doi.org/10.1007/s11033-022-07631-7

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