Journal ArticleDOI
LDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosis
Zhiyu Wang,Tjing Yung Loo,Jiangang Shen,Neng Wang,Dongmei Wang,Depo Yang,Sui Lin Mo,Xin Yuan Guan,Jianping Chen +8 more
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TLDR
The results suggested that LDH-A inhibition might offer a promising therapeutic strategy for breast cancer.Abstract:
LDH-A, as the critical enzyme accounting for the transformation from pyruvate into lactate, has been demonstrated to be highly expressed in various cancer cells and its silencing has also been approved relating to increased apoptosis in lymphoma cells. In this study, we intend to investigate the correlation between LDH-A and other clinicopathological factors of breast cancer and whether LDH-A silencing could suppress breast cancer growth, and if so the potential mechanisms. 46 breast cancer specimens were collected to study the relation between LDH-A expression and clinicopathological characteristics including menopause, tumor size, node involvement, differentiation, and pathological subtypes classified by ER, PR, and Her-2. shRNAs were designed and applied to silence LDH-A expression in breast cancer cell lines MCF-7 and MDA-MB-231. The effects of LDH-A reduction on cancer cells were studied by a series of in vitro and in vivo experiments, including cell growth assay, apoptosis evaluation, oxidative stress detection, transmission electron microscopy observation, and tumor formation assay on nude mice. LDH-A expression was found to correlate significantly with tumor size and to be independent for other clinicopathological factors. LDH-A reduction resulted in an inhibited cancer cell proliferation, elevated intracellular oxidative stress, and induction of mitochondrial pathway apoptosis. Meanwhile, the tumorigenic ability of LDH-A deficient cancer cells was significantly limited in both breast cancer xenografts. The Ki67 positive cancer cells were significantly reduced in LDH-A deficiency tumor samples, while the apoptosis ratio was enhanced. Our results suggested that LDH-A inhibition might offer a promising therapeutic strategy for breast cancer.read more
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Increased LDH5 expression is associated with lymph node metastasis and outcome in oral squamous cell carcinoma
TL;DR: Evidence that LDH5 expression in OSCC might be associated with tumour formation and metastasis in a large patient cohort is provided and adjuvant therapies targeting glucose metabolism might be promising for therapy of OSCC.
Journal ArticleDOI
Lactate dehydrogenase B is associated with the response to neoadjuvant chemotherapy in oral squamous cell carcinoma.
TL;DR: This study investigated the role of lactate dehydrogenase B (LDHB), a key glycolytic enzyme catalyzing the inter-conversion between pyruvate and lactate, in determining chemotherapy response and prognosis in oral squamous cell carcinoma patients and discovered that a high protein level of LDHB in OSCC patients was associated with a poor response to TPF regimen chemotherapy.
Journal ArticleDOI
Metabolic Plasiticy in Cancers-Distinct Role of Glycolytic Enzymes GPI, LDHs or Membrane Transporters MCTs.
Maša Ždralević,Ibtissam Marchiq,Monique Meyenberg Cunha de Padua,Scott K. Parks,Jacques Pouysségur +4 more
TL;DR: The benefits and limitations of disrupting fermentative glycolysis for impeding tumor growth at three levels of the pathway are discussed and the responses of different cancer cell lines in terms of metabolic rewiring, growth arrest, and tumor escape are discussed.
Journal ArticleDOI
'Warburg effect' controls tumor growth, bacterial, viral infections and immunity - Genetic deconstruction and therapeutic perspectives.
TL;DR: In this paper , the Warburg effect via CRISPR-Cas9 disruption of glucose-6-phosphate isomerase (GPI-KO) or lactate dehydrogenases (LDHA/B-DKO) is revisited.
Journal ArticleDOI
Silencing LDHA inhibits proliferation, induces apoptosis and increases chemosensitivity to temozolomide in glioma cells
Hui Di,Xinting Zhang,Yi Guo,Yanfang Shi,Chuan Fang,Yu Yuan,Jiwei Wang,Chao Shang,Wenzhe Guo,Chunhui Li +9 more
TL;DR: There is a significant positive correlation between LDHA expression levels and tumor clinical stages and the knockdown of LDHA inhibited cell growth by inhibiting cell cycle progression and inducing apoptosis in glioma cell lines.
References
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mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt
Kathryn E. O'Reilly,Fredi Rojo,Qing-Bai She,David B. Solit,Gordon B. Mills,Debra G. Smith,Heidi Lane,Francesco Hofmann,Daniel J. Hicklin,Dale L. Ludwig,José Baselga,Neal Rosen +11 more
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Glycolysis inhibition for anticancer treatment
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