Telmisartan Influences the Antiproliferative Activity of Linoleic Acid in Human Colon Cancer Cells

Abstract

Aim: Linoleic acid (LA) and telmisartan as PPARgamma agonists exhibit anticancer activity. The LA effect is observed for high non-achievable in vivo concentrations and in short treatment period, therefore we evaluate the effect of supplemental LA and pharmacological telmisartan plasma concentrations on human primary (SW480) and metastatic (SW620) colon cancer cells and immortal keratinocytes (HaCaT) cells in long-term treatment.

Methods: Cell viability and proliferation were determined by TB and MTT and pro-apoptotic effect was measured by Annexin V binding assays, respectively.

Results: LA decreased cancer cell viability and proliferation in a concentration-dependent manner, whereas no significant effect was found for HaCaT cells. Telmisartan (0.2 µM) suppresses antiproliferative effect of 60 µM LA on cancer cells in short-term treatment. Long-term administration of 60 µM LA reduced cancer cells viability after one week, while telmisartan delayed this effect by two weeks. Growth of all cell lines with 20 µM LA was unchanged during all treatment time. Telmisartan decreased late apoptosis of cancer and normal cells with 60 and 120 µM LA.

Conclusion: The cytotoxic LA action depends not only on its concentration but also duration of treatment. Telmisartan exhibits biphasic but not synergistic effect on LA cytotoxicity in cancer cells.

Acknowledgments

The authors would like to thank Jolanta Surdyk, MSci for skillful technical assistance.

Disclosure Statement

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by grant 1WK/N/2017/2017 from the Medical University of Warsaw, Poland. MTT assay was performed using CePT consortium infrastructure financed by the European Regional Development Fund within the operational program Innovative economy for 2007–2013