Lonidamine is a selective inhibitor that inhibits aerobic glycolysis in murine tumor cells. Lonidamine at a concentration of 0.32mM reduced the respiration of germ cells and submaxillary gland cells by 58%. Treatment of Serotoli’s cells and hepatocytes with lonidamine led to 16% and 6% inhibition of oxygen consumption, respectively. Lonidamine at the same concentration inhibited oxygen consumption of Ehrlich ascites tumor cells and sarcoma 180 cells by 58 and 63%, respectively, but enhanced aerobic glycolysis in normal cells, such as germ cells (57%) and submaxillary gland cells (35%). Lonidamine at a concentration of 20mM reduced the amount of glucose 6-phosphate formed by the mitochondria of Ehrlich ascites tumor cells by >50%.[2] Lonidamine inhibited glioma cell proliferation with an IC50 value of 200μM. Treatment of SNb-19 cells with 100 or 200μM lonidamine resulted in a slight decrease in the S-phase component of the cell cycle (3% and 9%, respectively). The administration of nude mice with lonidamine (160 mg/kg body weight/day) and diazepam (1 mg/kg body weight/day) via intraperitoneal injection for 10 days inhibited the growth of TG-8-OZ glioma xenograft (78% inhibition) 7 days after the treatment.[1]
作用机制
Lonidamine is a derivative of indazole-3-carboxylic acid that affects energy metabolism in tumor cells by inhibiting mitochondria-bound hexokinase and the electron transport chain.[1]
Lonidamine/氯尼达明 细胞实验
Cell Line
Concentration
Treated Time
Description
References
4T1 cells
0.1 mg/mL
12 hours
Evaluate the photothermal therapeutic effect of BTN@LND NPs on 4T1 cells, results showed that BTN@LND + L group caused over 95% cell death after 1064 nm laser irradiation
J Nanobiotechnology. 2024 Apr 10;22(1):163.
LM3 cells
15 µg/mL
12 hours
To evaluate the inhibitory effect of LND on glycolysis, the results showed that LND significantly reduced extracellular lactate levels, indicating that LND effectively inhibited glycolysis.
J Nanobiotechnology. 2023 Dec 15;21(1):482.
MDA-MB-231 cells
40 μg/mL
24 hours
To evaluate the apoptosis-inducing effect of LND-PLGA/TPS/DSSR NPs on MDA-MB-231 cells, the results showed that LND-PLGA/TPS/DSSR NPs significantly increased the proportion of early and late apoptotic cells.
Int J Nanomedicine. 2023 Jul 24;18:4023-4042.
LM3 cells
15 µg/mL
24 hours
To evaluate the inhibitory effect of LND on HK activity, the results showed that LND significantly reduced intracellular HK levels, indicating a significant inhibitory effect of LND on HK activity.
J Nanobiotechnology. 2023 Dec 15;21(1):482.
Bone marrow-derived macrophages (BMDMs)
200 µM
30 minutes
LND inhibited NLRP3 inflammasome activation, reducing caspase-1 and IL-1β secretion.
J Neuroinflammation. 2022 Dec 28;19(1):315.
J774A.1 cells
200 µM
30 minutes
LND inhibited NLRP3 inflammasome activation, reducing caspase-1 and IL-1β secretion.
J Neuroinflammation. 2022 Dec 28;19(1):315.
LM3 cells
15 µg/mL
4 hours
To evaluate the effect of LND on intracellular GSH levels, the results showed that LND significantly reduced intracellular GSH levels.
J Nanobiotechnology. 2023 Dec 15;21(1):482.
HCT 116
50 µM
48 hours
Lonidamine potentiated the oncolytic effect and increased the infection rate of M1 virus.
Cancer Cell Int. 2020 Nov 2;20(1):532.
HCT-8
50 µM
48 hours
Lonidamine potentiated the oncolytic effect and increased the infection rate of M1 virus.
Cancer Cell Int. 2020 Nov 2;20(1):532.
Lonidamine/氯尼达明 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c-nu/nu mice
HCT 116 tumor xenograft model
Intraperitoneal injection
10 mg/kg
Once daily for 5 days
Lonidamine in combination with M1 virus significantly inhibited tumor growth without affecting mouse body weight.
Cancer Cell Int. 2020 Nov 2;20(1):532.
BALB/c Nude mice
LM3 subcutaneous xenograft tumor models
Tail vein injection
15 µg/mL
Injected at days 1, 3 and 5, lasted for 18 days
To evaluate the effect of LND on tumor hypoxia, the results showed that LND significantly relieved tumor hypoxia. In addition, LND significantly reduced HSP90 expression in tumor tissues, enhancing the efficacy of photothermal therapy.
J Nanobiotechnology. 2023 Dec 15;21(1):482.
BALB/c mice
4T1 subcutaneous tumor model
Intravenous injection
2.0 mg/mL
Single injection, laser irradiation after 24 hours
Evaluate the anti-tumor effect of BTN@LND NPs in the 4T1 subcutaneous tumor model, results showed that BTN@LND + L group significantly inhibited tumor growth with only a 1.9-fold increase in tumor volume after 1064 nm laser irradiation
J Nanobiotechnology. 2024 Apr 10;22(1):163.
BALB/c Nude mice
TNBC MDA-MB-231 xenograft model
Intravenous injection
4 mg/kg
Every other day for 18 days
To evaluate the anti-tumor activity of LND-PLGA/TPS/DSSR NPs in the TNBC MDA-MB-231 xenograft model, the results showed that LND-PLGA/TPS/DSSR NPs significantly inhibited tumor growth and reduced the toxicity of LND.
Int J Nanomedicine. 2023 Jul 24;18:4023-4042.
C57BL/6 mice
LPS-induced sepsis model
Intraperitoneal injection
40 mg/kg and 60 mg/kg
Single injection
LND significantly alleviated the inflammatory response in the LPS-induced sepsis model, reducing serum levels of IL-1β and IL-18.
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