Anticancer activity of “Trigno M”, extract of Prunus spinosa drupes, against in vitro 3D and in vivo colon cancer models

Maria Condello, Evelin Pellegrini, Enrico Pierluigi Spugnini, Alfonso Baldi, Bruno Amadio, Bruno Vincenzi, Giovanni Occhionero, Sebastiano Delfine, Franco Mastrodonato, Stefania Meschini

Research output: Contribution to journalArticle

Abstract

In 2018 there were over 1.8 million new cases worldwide of colorectal cancer and relapses after clinical treatments. Many studies ascribe the risk of the appearance of this cancer to the Western life style: a sedentary life, obesity, and low -fiber, high -fat diets can promote the onset of disease. Several studies have shown supplement phytochemicals to have an inhibiting effect on the growth of various cancers through the activation of apoptosis. Our goal was to prove the effectiveness of a natural compound in the combined therapy of colorectal cancer. Trigno M supplement was an optimal candidate as anticancer product for its high concentrations of phenolic acids, flavonoids and anthocyanins. Our work showed the antitumor activity of Trigno M, extract of Prunus spinosa drupes combined with the nutraceutical activator complex (NAC), in 2D, 3D and in vivo colorectal cancer models. The cellular model we used both in vitro and in vivo was the HCT116 cell line, particularly suitable for engraftment after inoculation in mice. Trigno M inhibited the growth and colony formation of HCT116 cells (35%) as compared to the chemotherapy treatment with 5-fluorouracil (80%) used in clinical therapy. The reduction of the morphological dimensions in the spheroid cells after Trigno M, was compared with 5-fluorouracil demonstrating the efficacy of the Trigno M compound also in 3D models. Flow cytometric analysis on 3D cells showed a significant increase in the apoptotic cell fraction after Trigno M treatment (44.8%) and a low level of necrotic fraction (6.7%) as compared with control cells. Trigno M and 5-fluorouracil induced the apoptosis in a comparable percentage. Monotherapy with Trigno M in severely immunodeficient mice, carrying colon rectal cancer xenografts, significantly reduced tumor growth. The histopatological analysis of the ectopic tumors showed a lower level of necrosis after Trigno M treatment compared with the control. We conclude that Trigno M is well tolerated by mice, delays colorectal cancer growth in these animals and should be weighed up for integration of the current multi-drug protocols in the treatment of colon carcinoma.

Original languageEnglish
Article number109281
JournalBiomedicine and Pharmacotherapy
Volume118
DOIs
Publication statusPublished - Oct 2019

Fingerprint

Prunus
Colonic Neoplasms
Colorectal Neoplasms
Fluorouracil
HCT116 Cells
Growth
Neoplasms
Therapeutics
Apoptosis
Anthocyanins
Phytochemicals
High Fat Diet
Rectal Neoplasms
Clinical Protocols
Dietary Supplements
Flavonoids
Heterografts
In Vitro Techniques
Life Style
Colon

Keywords

  • 3D model
  • Anticancer activity
  • Colorectal cancer cells
  • In vivo mouse model
  • Trigno M

ASJC Scopus subject areas

  • Pharmacology

Cite this

Anticancer activity of “Trigno M”, extract of Prunus spinosa drupes, against in vitro 3D and in vivo colon cancer models. / Condello, Maria; Pellegrini, Evelin; Spugnini, Enrico Pierluigi; Baldi, Alfonso; Amadio, Bruno; Vincenzi, Bruno; Occhionero, Giovanni; Delfine, Sebastiano; Mastrodonato, Franco; Meschini, Stefania.

In: Biomedicine and Pharmacotherapy, Vol. 118, 109281, 10.2019.

Research output: Contribution to journalArticle

Condello, M, Pellegrini, E, Spugnini, EP, Baldi, A, Amadio, B, Vincenzi, B, Occhionero, G, Delfine, S, Mastrodonato, F & Meschini, S 2019, 'Anticancer activity of “Trigno M”, extract of Prunus spinosa drupes, against in vitro 3D and in vivo colon cancer models', Biomedicine and Pharmacotherapy, vol. 118, 109281. https://doi.org/10.1016/j.biopha.2019.109281
Condello, Maria ; Pellegrini, Evelin ; Spugnini, Enrico Pierluigi ; Baldi, Alfonso ; Amadio, Bruno ; Vincenzi, Bruno ; Occhionero, Giovanni ; Delfine, Sebastiano ; Mastrodonato, Franco ; Meschini, Stefania. / Anticancer activity of “Trigno M”, extract of Prunus spinosa drupes, against in vitro 3D and in vivo colon cancer models. In: Biomedicine and Pharmacotherapy. 2019 ; Vol. 118.
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abstract = "In 2018 there were over 1.8 million new cases worldwide of colorectal cancer and relapses after clinical treatments. Many studies ascribe the risk of the appearance of this cancer to the Western life style: a sedentary life, obesity, and low -fiber, high -fat diets can promote the onset of disease. Several studies have shown supplement phytochemicals to have an inhibiting effect on the growth of various cancers through the activation of apoptosis. Our goal was to prove the effectiveness of a natural compound in the combined therapy of colorectal cancer. Trigno M supplement was an optimal candidate as anticancer product for its high concentrations of phenolic acids, flavonoids and anthocyanins. Our work showed the antitumor activity of Trigno M, extract of Prunus spinosa drupes combined with the nutraceutical activator complex (NAC), in 2D, 3D and in vivo colorectal cancer models. The cellular model we used both in vitro and in vivo was the HCT116 cell line, particularly suitable for engraftment after inoculation in mice. Trigno M inhibited the growth and colony formation of HCT116 cells (35{\%}) as compared to the chemotherapy treatment with 5-fluorouracil (80{\%}) used in clinical therapy. The reduction of the morphological dimensions in the spheroid cells after Trigno M, was compared with 5-fluorouracil demonstrating the efficacy of the Trigno M compound also in 3D models. Flow cytometric analysis on 3D cells showed a significant increase in the apoptotic cell fraction after Trigno M treatment (44.8{\%}) and a low level of necrotic fraction (6.7{\%}) as compared with control cells. Trigno M and 5-fluorouracil induced the apoptosis in a comparable percentage. Monotherapy with Trigno M in severely immunodeficient mice, carrying colon rectal cancer xenografts, significantly reduced tumor growth. The histopatological analysis of the ectopic tumors showed a lower level of necrosis after Trigno M treatment compared with the control. We conclude that Trigno M is well tolerated by mice, delays colorectal cancer growth in these animals and should be weighed up for integration of the current multi-drug protocols in the treatment of colon carcinoma.",
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