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Medicinal Chemistry Research

, Volume 29, Issue 3, pp 377–395 | Cite as

Styrylcoumarin 7-SC2 induces apoptosis in SW480 human colon adenocarcinoma cells and inhibits azoxymethane-induced aberrant crypt foci formation in BALB/c mice

  • Angie Herrera-REmail author
  • Tonny W. Naranjo
  • Maria Elena Maldonado
  • Gustavo Moreno-Q
  • Andrés Yepes
  • Wilson Cardona-GEmail author
Original Research
  • 36 Downloads

Abstract

In vivo chemopreventive effects associated with hybrid molecules against colon carcinogenesis remain poorly studied. In a previous study, we showed that styrylcoumarin hybrids 3-SC1, 7-SC2 (2,7-(4-hydroxy-3,5-dimethoxystyryl)-coumarin), and 7-SC3 decrease cell viability of SW480 in a time- and concentration-dependent manner (IC50-SW480/48 h = 6.92; 1.01 and 5.33 µM, respectively) with high selectivity indices after 48 h of treatment (>400; 67.8 and 7.2, respectively). The present study investigates the mechanisms of these three styrylcoumarins to induce cell death, using an in vitro model of colon adenocarcinoma cells (SW480); besides, it evaluates anticarcinogenic properties in vivo for the most active molecule. According to the results, none of the hybrids exhibited significant changes in cell cycle distribution of SW480 cells with respect to control group (G0/G1 = 85.5%, S = 7.2%, and G2/M 7.3%), which indicates that these do not have a cytostatic effect on this cell line. Besides, they did not cause mitochondrial depolarization, suggesting an alternative source for the production of reactive oxygen species (ROS). Among the evaluated compounds, the most active molecule 7-SC2 induced a greater production of ROS in comparison with the control (p < 0.05) together with a significant increase in the expression of p53, caspase-3, and a significant reduction in the production of interleukin-6 of SW480 cells. When colon carcinogenesis was induced in Balb/c mice by intraperitoneal injections of azoxymethane, a significant reduction (p < 0.05) in the number of preneoplastic lesions of mice treated with styrylcoumarin hybrid 7-SC2 was observed with regard to the control group. In addition, no side effects were associated with the administration of the compound. All these in vitro results and the effective reduction of preneoplastic lesions in vivo suggest that styrylcoumarin 7-SC2 induces apoptosis in primary tumor cells and implies the potential ability at the early post-initiation phases of colon carcinogenesis. Moreover, hybrid 7-SC2 was docked to the three-dimensional structures of different apoptotic proteins and inflammatory cytokines, showing high binding affinities (ranging from −10.0 to −7.2 kcal/mol). Good correlation between calculated binding energies and experimental results was obtained. According to in silico ADME (absorption, distribution, metabolism, and excretion) studies of the 7-SC2, this novel compound has suitable drug-like properties, making it a potentially promising agent for therapy against colon cancer.

Keywords

Styrylcoumarin Cell death Aberrant crypt foci Colorectal cancer In silico studies 

Abbreviations

CRC

Colorectal cancer

ACF

Aberrant crypt foci

AOM

Azoxymethane

SS

Saline solution

DMSO

Dimethylsulfoxide

APTES

(3-Aminopropyl)triethoxysilane

Notes

Acknowledgements

We thank the University of Antioquia (grant CODI 2014-808) for financial support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Angie Herrera-R
    • 1
    • 2
    Email author
  • Tonny W. Naranjo
    • 3
    • 4
  • Maria Elena Maldonado
    • 2
  • Gustavo Moreno-Q
    • 1
  • Andrés Yepes
    • 1
  • Wilson Cardona-G
    • 1
    Email author
  1. 1.Química de Plantas Colombianas, Institute of Chemistry, Faculty of Exact and Natural SciencesUniversity of Antioquia, UdeAMedellínColombia
  2. 2.Grupo Impacto de los Componentes Alimentarios en la Salud, School of Dietetics and NutritionUniversity of AntioquiaMedellínColombia
  3. 3.Grupo de Micología Médica y ExperimentalCorporación para Investigaciones BiológicasMedellínColombia
  4. 4.School of Health SciencesUniversidad Pontificia BolivarianaMedellínColombia

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