microRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells

One of the compounds found efficacious as an anti-proliferative on colon cancer is alpha-mangosteen, a xanthon compound that is abundant in pericarp of mangosteen. This study focused to evaluate anticancer activity of the ethanolic extract of pericarp of mangosteen (Garcinia mangostana Linn.) on WiDr colon cancer cells and to observe the affinity of alpha-mangosteen in inhibiting IKK and VEGF. Cytotoxic effect was tested by MTT assay and apoptosis induction was evaluated by double staining method on WiDr colon cancer cells, while interaction between alpha-mangosteen to the receptors was measured by molecular docking. The ethanolic extract was proven to have cytotoxic activity against WiDr colon cancer cells with IC50 of 25 µg/mL. In addition, the observation of apoptosis induction by double-staining method showed that apoptosis associated the cytotoxic effect of ethanolic extract of pericarp of mangosteen (EPM) on WiDr colon cancer cells. Molecular docking showed that active compounds in pericarp of mangosteen could compete with the native ligand of VEGF because the docking score of alpha-mangosteen was almost equal with native ligand. From these results we could be concluded that the cytotoxic effect of EPM to WiDr cells was mediated by cell apoptosis. This extract was potential to be developed as chemopreventive agent.Keywords : Garcinia mangostana Linn., cytotoxic effect, apoptosis, WiDr cell, molecular docking

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MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01115-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Shaobo Bai ◽

Yang Sun ◽

Ying Cheng ◽

Weiliang Ye ◽

Chenchao Jiang ◽

...

Keyword(s):

Colon Cancer ◽

Calcium Phosphate ◽

Protein Expression ◽

Cancer Cells ◽

Active Targeting ◽

Cancer Targeting ◽

Drug Resistant ◽

Colon Cancer Cells ◽

Apoptosis Pathway ◽

Calcium Phosphate Nanoparticles

Abstract Background Colon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis. Paris saponin VII (PSVII) could not only inhibit the proliferation of colon cancer cells but also effectively induce apoptosis of drug-resistant colon cancer cells and reduce the metastasis of drug-resistant colon cancer cells as well. However, PSVII was insoluble in water and fat. It displayed no selective distribution in body and could cause severe hemolysis. Herein, colon cancer targeting calcium phosphate nanoparticles were developed to carry PSVII to treat drug-resistant colon cancer. Results PSVII carboxymethyl-β-cyclodextrin inclusion compound was successfully encapsulated in colon cancer targeting calcium phosphate nanoparticles (PSVII@MCP-CaP) by using modified citrus pectin as stabilizer agent and colon cancer cell targeting moiety. PSVII@MCP-CaP significantly reduced the hemolysis of PSVII. Moreover, by specific accumulating in orthotopic drug-resistant colon cancer tissue, PSVII@MCP-CaP markedly inhibited the growth of orthotopic drug-resistant colon cancer in nude mice. PSVII@MCP-CaP promoted the apoptosis of drug-resistant colon cancer cells through mitochondria-mediated apoptosis pathway. Moreover, PSVII@MCP-CaP significantly inhibited the invasion and migration of drug-resistant colon cancer cells by increasing E-cadherin protein expression and reducing N-cadherin and MMP-9 protein expression. Conclusion PSVII@MCP-CaP has great potential in the treatment of drug-resistant colon cancer. This study also explores a new method to prepare active targeting calcium phosphate nanoparticles loaded with a fat and water insoluble compound in water. Graphical Abstract

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