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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Cell+Biochem+Biophys
2016 ; 74
(3
): 427-34
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Oleanolic Acid Inhibits High Salt-Induced Exaggeration of Warburg-like Metabolism
in Breast Cancer Cells
#MMPMID27236294
Amara S
; Zheng M
; Tiriveedhi V
Cell Biochem Biophys
2016[Sep]; 74
(3
): 427-34
PMID27236294
show ga
Cancer cells have a proliferative advantage by utilizing intermediates of aerobic
glycolysis (Warburg effect) for their macromolecule synthesis. Although the exact
causes of this Warburg effect are unclear, high osmotic stress in solid tumor
microenvironment is considered one of the important factors. Oleanolic acid (OA)
is known to exert anti-inflammatory and anti-cancer effect. In our current
studies, using breast cancer cell lines, we determined the protective role of OA
in high salt-mediated osmotic stress-induced cancer growth. Hypertonic (0.16 M
NaCl) culture conditions enhanced the cancer cell growth (26 %, p < 0.05) and
aerobic glycolysis as marked by increased glucose consumption (34 %, p < 0.05)
and lactate production (25 %, p < 0.05) over untreated cells. This effect was
associated with increased expression and activity of key rate-limiting enzymes of
aerobic glycolysis, namely hexokinase, pyruvate kinase type M2, and lactate
dehydrogenase A. Interestingly, this high salt-mediated enhanced expression of
aerobic glycolytic enzymes was efficiently reversed by OA along with the
decreased cancer cell proliferation. In cancer cells, enhanced aerobic glycolysis
is associated with the decreased mitochondrial activity and
mitochondrial-associated caspase activity. As expected, high salt further
inhibited the mitochondrial related cytochrome oxidase and caspase-3 activity.
However, OA efficiently reversed the high salt-mediated inhibition of cytochrome
oxidase, caspase activity, and pro-apoptotic Bax expression, thus suggesting that
OA induced mitochondrial activity and enhanced apoptosis. Taken together, our
data indicate that OA efficiently reverses the enhanced Warburg-like metabolism
induced by high salt-mediated osmotic stress along with potential application of
OA in anti-cancer therapy.
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