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Salinomycin and Sulforaphane Exerted Synergistic Antiproliferative and Proapoptotic Effects on Colorectal Cancer

Fang Liu1,2, Rong-Bin Lv3, Yan Liu4

  • 1Department of Geriatric Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People's Republic of China.

Oncotargets and Therapy
|June 26, 2020
PubMed
Abstract

Insights

Combining salinomycin (SAL) and sulforaphane (SFN) shows synergistic effects against colorectal cancer (CRC) by inhibiting proliferation and inducing apoptosis. This novel combination may offer a new therapeutic strategy for CRC treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Salinomycin (SAL) and sulforaphane (SFN) have demonstrated antitumorigenic properties in various cancers.
  • Colorectal cancer (CRC) remains a significant health concern, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To investigate the synergistic antiproliferative and proapoptotic effects of combining SAL and SFN in CRC cells.
  • To evaluate the efficacy of this combination in vitro and in vivo models of CRC.

Main Methods:

  • Synergistic effects were assessed using the Chou-Talalay method to calculate the combination index (CI).
  • In vitro studies involved evaluating proliferation, migration, invasion, and apoptosis in CRC cell lines.
  • In vivo efficacy was tested using a xenograft model.

Main Results:

  • The combination of SAL and SFN significantly inhibited CRC cell proliferation, migration, and invasion while enhancing apoptosis.
  • Molecular analysis revealed that the combination treatment induced apoptosis by inhibiting the PI3K/Akt pathway, upregulating p53 and Bax, downregulating Bcl-2, and increasing the Bax/Bcl-2 ratio.
  • Enhanced poly ADP-ribose polymerase (PARP) cleavage was observed, indicating increased apoptosis, particularly when the PI3K/Akt pathway was pre-inhibited.

Conclusions:

  • The combination of SAL and SFN exhibits potent antiproliferative and proapoptotic activities against CRC cells.
  • This synergistic combination demonstrated superior efficacy compared to monotherapies in reducing tumor growth, migration, and invasion.
  • The findings suggest that the SAL-SFN combination represents a promising novel therapeutic strategy for colorectal cancer treatment.
Keywords:
PI3K/Akt pathwayapoptosiscolorectal cancersalinomycinsulforaphanesynergism

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