N-(3-oxo-acyl) homoserine lactone inhibits tumor growth independent of Bcl-2 proteins

Zhao, Guoping; Neely, Aaron M.; Schwarzer, Christian; Han, Lu; Whitt, Aaron G.; Stivers, Nicole S.; Burlison, Joseph A.; White, Carl; Machen, Terry E.; Li, Chi

doi:10.18632/oncotarget.6827

Cited by 17 publications

(35 citation statements)

References 59 publications

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“…Quorum sensing is a bacterial communication system that releases and detects small diffusible autoinducers (8,58). This system is responsible for the regulation of bacterial gene expression in response to changes in cell population density (58).…”

Section: N-(3-oxododecanoyl)-homoserine Lactone (C12)mentioning

confidence: 99%

“…Akt/PKB pathway and attenuating STAT3 activity in breast carcinoma cells (8,66). In pancreatic carcinoma cells, C12 induces apoptotic signaling and inhibits cell migration (8,70).…”

Section: C12 Induces Apoptosis By Inhibiting Phosphatidylinositide3-kmentioning

confidence: 99%

“…In pancreatic carcinoma cells, C12 induces apoptotic signaling and inhibits cell migration (8,70). In colorectal cancer cells, C12 reduces the expression of thymidylate synthase while enhancing the activity of otherwise conventional chemotherapeutic agents including 5-fluorouracil (5-FU) (69).…”

Section: C12 Induces Apoptosis By Inhibiting Phosphatidylinositide3-kmentioning

confidence: 99%

“…PON2 expression also prevents NHBE and hT/LT/Ras cells were grown in BEGM supplemented with SingleQuots (LONZA). HCT116 cells were grown as described previously (8).…”

Section: Paraoxonase 2 (Pon2)mentioning

confidence: 99%

“…Previous studies indicate that C12 requires the lactonase / arylesterase PON2 to exert its cytotoxicity (8,9). …”

Section: Chapter 1: Introductionmentioning

confidence: 99%

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Modulation of cell death signaling and cell proliferation by the interaction of homoserine lactones and Paraoxonase 2.

Neely¹

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Section: N-(3-oxododecanoyl)-homoserine Lactone (C12)mentioning

confidence: 99%

“…Akt/PKB pathway and attenuating STAT3 activity in breast carcinoma cells (8,66). In pancreatic carcinoma cells, C12 induces apoptotic signaling and inhibits cell migration (8,70).…”

Section: C12 Induces Apoptosis By Inhibiting Phosphatidylinositide3-kmentioning

confidence: 99%

Section: C12 Induces Apoptosis By Inhibiting Phosphatidylinositide3-kmentioning

confidence: 99%

“…PON2 expression also prevents NHBE and hT/LT/Ras cells were grown in BEGM supplemented with SingleQuots (LONZA). HCT116 cells were grown as described previously (8).…”

Section: Paraoxonase 2 (Pon2)mentioning

confidence: 99%

“…Previous studies indicate that C12 requires the lactonase / arylesterase PON2 to exert its cytotoxicity (8,9). …”

Section: Chapter 1: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Modulation of cell death signaling and cell proliferation by the interaction of homoserine lactones and Paraoxonase 2.

Neely¹

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N-(3-oxo-acyl) homoserine lactone induced germ cell apoptosis and suppressed the over-activated RAS/MAPK tumorigenesis via mitochondrial-dependent ROS in C. elegans

et al. 2018

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As a quorum-sensing molecule for bacteria-bacteria communication, N-(3-oxododecanoyl)-homoserine lactone (C12) has been found to possess pro-apoptotic activities in various cell culture models. However, the detailed mechanism of how this important signaling molecule function in the cells of live animals still remains largely unclear. In this study, we systematically investigated the mechanism for C12-mediated apoptosis and studied its anti-tumor effect in Caenorhabditis elegans (C. elegans). Our data demonstrated that C12 increased C. elegans germ cell apoptosis, by triggering mitochondrial outer membrane permeabilization (MOMP) and elevating the reactive oxygen species (ROS) level. Importantly, C12-induced ROS increased the expression of genes critical for DNA damage response (hus-1, clk-2 and cep-1) and genes involved in p38 and JNK/MAPK signaling pathway (nsy-1, sek-1, pmk-1, mkk-4 and jnk-1). Furthermore, C12 failed to induce germ cell apoptosis in animals lacking the expression of each of those genes. Finally, in a C. elegans tumor-like symptom model, C12 significantly suppressed tumor growth through inhibiting the expression of RAS/MAPK pathway genes (let-23/EGFR, let-60/RAS, lin-45/RAF, mek-2/MEK and mpk-1/MAPK). Overall, our results indicate that DNA damage response and MAPK activation triggered by mitochondrial ROS play important roles in C12-induced apoptotic signaling in C. elegans, and RAS/MAPK suppression is involved in the tumor inhibition effect of C12. This study provides in vivo evidence that C12 is a potential candidate for cancer therapeutics by exerting its pro-apoptotic and anti-tumor effects via elevating mitochondria-dependent ROS production.

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Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl) homoserine lactone induces calcium signaling-dependent crosstalk between autophagy and apoptosis in human macrophages

Kushwaha

Verma

Agarwal

2022

Cellular Signalling

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N-(3-oxo-acyl) homoserine lactone inhibits tumor growth independent of Bcl-2 proteins

Cited by 17 publications

References 59 publications

Modulation of cell death signaling and cell proliferation by the interaction of homoserine lactones and Paraoxonase 2.

Modulation of cell death signaling and cell proliferation by the interaction of homoserine lactones and Paraoxonase 2.

N-(3-oxo-acyl) homoserine lactone induced germ cell apoptosis and suppressed the over-activated RAS/MAPK tumorigenesis via mitochondrial-dependent ROS in C. elegans

Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl) homoserine lactone induces calcium signaling-dependent crosstalk between autophagy and apoptosis in human macrophages

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