Low-Dose Paclitaxel Inhibits Tumor Cell Growth by Regulating Glutaminolysis in Colorectal Carcinoma Cells

Paclitaxel (PTX) is a natural alkaloid isolated from the bark of a tree, , and is currently used to treat a variety of tumors. Recently, it has been found that low-dose PTX is a promising treatment for some cancers, presenting few side effects. However, antitumor mechanisms of low-dose PTX (<1 nM...

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Published inFrontiers in pharmacology Vol. 8; p. 244
Main Authors Lv, Chaoxiang, Qu, Hao, Zhu, Wanyun, Xu, Kaixiang, Xu, Anyong, Jia, Baoyu, Qing, Yubo, Li, Honghui, Wei, Hong-Jiang, Zhao, Hong-Ye
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 04.05.2017
Subjects
cell growth
colorectal carcinoma cells
glutaminolysis
lactate production
low-dose PTX
Pharmacology
cell growth
low-dose PTX
lactate production
colorectal carcinoma cells
glutaminolysis
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Summary:Paclitaxel (PTX) is a natural alkaloid isolated from the bark of a tree, , and is currently used to treat a variety of tumors. Recently, it has been found that low-dose PTX is a promising treatment for some cancers, presenting few side effects. However, antitumor mechanisms of low-dose PTX (<1 nM) have rarely been illuminated. Here we report a new antitumor mechanism of low-dose PTX in colorectal carcinoma cells. We treated colorectal carcinoma HCT116 cells with PTX at 0.1 and 0.3 nM for 0, 1, 2, or 3 days, and found that low-dose PTX inhibits cell growth without altering cell morphology and cell cycle. There was a significant decrease of pH in culture media with 0.3 nM PTX for 3 days. Also, lactate production was significantly increased in a dose- and time-dependent manner. Furthermore, expression of glutaminolysis-related genes and were significantly decreased in the colorectal carcinoma cells treated with low-dose PTX. Meanwhile, protein expression levels of p53 and p21 increased significantly in colorectal carcinoma cells so treated. In summary, low-dose PTX down-regulated glutaminolysis-related genes and increased their lactate production, resulting in decreased pH of tumor microenvironments and inhibition of tumor cell growth. Up-regulation of p53 and p21 in colorectal carcinoma cells treated with low-dose PTX also contributed to inhibition of tumor cell growth.
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Edited by: Owen McCarty, Oregon Health & Science University, USA
Reviewed by: Xin Wang, Stanford University, USA; Ying Luo, Kunming University of Science and Technology, China
These authors have contributed equally to this work.
This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Pharmacology
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2017.00244