CLC number:
On-line Access: 2023-05-15
Received: 2022-07-03
Revision Accepted: 2022-12-07
Crosschecked: 2023-05-16
Cited: 0
Clicked: 985
Huan CHEN, Kunming LIANG, Cong HOU, Hai-long PIAO. Dichloroacetic acid and rapamycin synergistically inhibit tumor progression[J]. Journal of Zhejiang University Science B, 2023, 24(5): 397-405.
@article{title="Dichloroacetic acid and rapamycin synergistically inhibit tumor progression",
author="Huan CHEN, Kunming LIANG, Cong HOU, Hai-long PIAO",
journal="Journal of Zhejiang University Science B",
volume="24",
number="5",
pages="397-405",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200356"
}
%0 Journal Article
%T Dichloroacetic acid and rapamycin synergistically inhibit tumor progression
%A Huan CHEN
%A Kunming LIANG
%A Cong HOU
%A Hai-long PIAO
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 5
%P 397-405
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200356
TY - JOUR
T1 - Dichloroacetic acid and rapamycin synergistically inhibit tumor progression
A1 - Huan CHEN
A1 - Kunming LIANG
A1 - Cong HOU
A1 - Hai-long PIAO
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 5
SP - 397
EP - 405
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200356
Abstract: Mammalian target of rapamycin (mTOR) controls cellular anabolism, and mTOR signaling is hyperactive in most cancer cells. As a result, inhibition of mTOR signaling benefits cancer patients. rapamycin is a US Food and Drug Administration (FDA)-approved drug, a specific mTOR complex 1 (mTORC1) inhibitor, for the treatment of several different types of cancer. However, rapamycin is reported to inhibit cancer growth rather than induce apoptosis. Pyruvate dehydrogenase complex (PDHc) is the gatekeeper for mitochondrial pyruvate oxidation. PDHc inactivation has been observed in a number of cancer cells, and this alteration protects cancer cells from senescence and nicotinamide adenine dinucleotide (NAD+) exhaustion. In this paper, we describe our finding that rapamycin treatment promotes pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) phosphorylation and leads to PDHc inactivation dependent on mTOR signaling inhibition in cells. This inactivation reduces the sensitivity of cancer cells’ response to rapamycin. As a result, rebooting PDHc activity with dichloroacetic acid (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, promotes cancer cells’ susceptibility to rapamycin treatment in vitro and in vivo.
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