In:
The American Journal of Chinese Medicine, World Scientific Pub Co Pte Ltd, Vol. 48, No. 01 ( 2020-01), p. 201-222
Abstract:
Aggressive tumor cells mainly rely on glycolysis, and further release vast amounts of lactate and protons by monocarboxylate transporter (MCT), which causes a higher intracellular pH (pH i ) and acidic extracellular pH. Isoorientin, a principle flavonoid compound extracted from several plant species, shows various pharmacological activities. However, effects of isoorientin on anticancer and MCT await to explore in human lung cancer cells. Human lung cancer tissues were obtained from cancer patients undergoing surgery, while the human lung adenocarcinoma cells (A549) were bought commercially. Change of pH i was detected by microspectrofluorometry method with a pH-sensitive fluorescent dye, BCECF. MTT and wound-healing assay were used to detect the cell viability and migration, respectively. Western blot techniques and immunocytochemistry staining were used to detect the protein expression. Our results indicated that the expression of MCTs1/4 and CD147 were upregulated significantly in human lung tissues. In experiments of A549 cells, under HEPES-buffer, the resting pH i was 7.47, and isoorientin (1–300[Formula: see text][Formula: see text] M) inhibited functional activity of MCT concentration-dependently (up to [Formula: see text]%). Pretreatment with isoorientin (3–100[Formula: see text] [Formula: see text]M) for 24[Formula: see text] h, MCT activity and cell migration were significantly inhibited ([Formula: see text]% and [Formula: see text] %, respectively), while the cell viability was not affected. Moreover, the expression of MCTs1/4, CD147, and matrix metalloproteinase (MMP) 2/9 were significantly down regulated. In summary, MCTs1/4 and CD147 are significantly upregulated in human lung adenocarcinoma tissues, and isoorientin inhibits cells-migration by inhibiting activity/expression of MCTs1/4 and MMPs2/9 in human lung cancer cells. These novel findings suggest that isoorientin could be a promising pharmacological agent for lung cancer.
Type of Medium:
Online Resource
ISSN:
0192-415X
,
1793-6853
DOI:
10.1142/S0192415X20500111
Language:
English
Publisher:
World Scientific Pub Co Pte Ltd
Publication Date:
2020
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