Abstract
BackgroundNatural products, especially those with high contents of phytochemicals, are promising alternative medicines owing to their antitumor properties and few side effects. In this study, the effects of a plant-based medicinal food (PBMF) composed of six medicinal and edible plants, namely, Coix seed, Lentinula edodes, Asparagus officinalis L., Houttuynia cordata, Dandelion, and Grifola frondosa, on gastric cancer and the underlying molecular mechanisms were investigated in vivo.MethodsA subcutaneous xenograft model of gastric cancer was successfully established in nude mice inoculated with SGC-7901 cells. The tumor-bearing mice were separately underwent with particular diets supplemented with three doses of PBMF (43.22, 86.44, and 172.88 g/kg diet) for 30 days. Tumor volumes were recorded. Histopathological changes in and apoptosis of the xenografts were evaluated by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, respectively. Serum levels of TNF-α, MMP-2, and MMP-9 were detected by enzyme-linked immunosorbent assay. The mRNA expression levels of β-catenin, GSK-3β, E-cadherin, N-cadherin, MMP-2/9, Snail, Bax, Bcl-2, Caspase-3/9, and Cyclin D1 were evaluated via real-time quantitative polymerase chain reaction. The protein expression levels of GSK-3β, E-cadherin, N-cadherin, and Ki-67 were determined by immunohistochemistry staining.ResultsPBMF treatment efficiently suppressed neoplastic growth, induced apoptosis, and aggravated necrosis in the xenografts of SGC-7901 cells. PBMF treatment significantly decreased the serum levels of MMP-2 and MMP-9 and significantly increased that of TNF-α. Furthermore, PBMF treatment notably upregulated the mRNA expression levels of GSK-3β, E-cadherin, Bax, Caspase-3, and Caspase-9 but substantially downregulated those of β-catenin, N-cadherin, MMP-2, MMP-9, Snail, and Cyclin D1 in tumor tissues. The Bax/Bcl-2 ratio was upregulated at the mRNA level. Moreover, PBMF treatment remarkably increased the protein expression levels of GSK-3β and E-cadherin but notably reduced those of Ki-67 and N-cadherin in tumor tissues.ConclusionsThe PBMF concocted herein exerts anti-gastric cancer activities via epithelial–mesenchymal transition reversal, apoptosis induction, and proliferation inhibition. The underlying molecular mechanisms likely rely on suppressing the Wnt/β-catenin signaling pathway.
Highlights
Gastric carcinoma (GC) is the fifth most prevalent malignancy with approximately 1,033,701 new cases reported annually; it is the third leading cause of cancer-related mortality, accounting for about 782, 685 deaths every year in both sexes worldwide [1]
Numerous in vivo and in vitro experimental studies have demonstrated that Coix seed, Lentinula edodes, Asparagus officinalis L., Houttuynia cordata, Dandelion, and Grifola frondosa have potent anticancer properties, such as antiproliferation, antimetastasis, and apoptosis induction; they have functional bioactive constituents involving a wide range of phytochemicals, such as flavonoids, alkaloids, saponins, terpenoids, polysaccharides, and others [9,10,11,12,13,14]
We aimed to investigate the therapeutic effects of a plant-based medicinal food (PBMF) developed from the aforementioned medicinal and edible plants on GC by using a subcutaneous xenograft model in nude mice from SGC-7901 cells and explore the underlying mechanisms
Summary
Gastric carcinoma (GC) is the fifth most prevalent malignancy with approximately 1,033,701 new cases reported annually; it is the third leading cause of cancer-related mortality, accounting for about 782, 685 deaths every year in both sexes worldwide [1]. Numerous in vivo and in vitro experimental studies have demonstrated that Coix seed, Lentinula edodes, Asparagus officinalis L., Houttuynia cordata, Dandelion, and Grifola frondosa have potent anticancer properties, such as antiproliferation, antimetastasis, and apoptosis induction; they have functional bioactive constituents involving a wide range of phytochemicals, such as flavonoids, alkaloids, saponins, terpenoids, polysaccharides, and others [9,10,11,12,13,14] Natural products, especially those with high contents of phytochemicals, are promising alternative medicines owing to their antitumor properties and few side effects. The effects of a plant-based medicinal food (PBMF) composed of six medicinal and edible plants, namely, Coix seed, Lentinula edodes, Asparagus officinalis L., Houttuynia cordata, Dandelion, and Grifola frondosa, on gastric cancer and the underlying molecular mechanisms were investigated in vivo
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