Telocinobufagin (Telobufotoxin; Telocinobufogenin) is an orally active bufadienolide with potential anti-tumor effects. Telocinobufagin exerts its anti-cancer effects on non-small cell carcinoma, osteosarcoma, thyroid cancer, breast cancer and head and neck squamous cell carcinoma by inhibiting the STAT3, JAK2/STAT3, LARP1-mTOR, PI3K/Akt/Snail and PLK1 pathways, and can also induce tumor cell apoptosis. Telocinobufagin enhances the Th1 immune response and protects against Salmonella typhimuriuminfection. Telocinobufagin has a strong cardiac-stimulating effect by inhibiting the activity of Na+/K+-ATPase, and it can promote renal fibrosis. Telocinobufagin demonstrates non-opioid analgesic effects in various acute pain models[1][2][3][4][5][6][7][8][9].
Inhibited cell viability in a concentration-dependent manner, and the corresponding half-maximal inhibitory concentrations (IC50) were 124.4, 618.5, and 106.6 nM, respectively.
Strongly upregulated cleaved PARP1 protein, but down-regulated anti-apoptotic BCL2 protein.
Inhibited STAT3 phosphorylation at tyrosine 705 (Y705) and its downstream targets.
Inhibited STAT3 nuclear translocation in a concentration-dependent manner.
Exhibited a dose-dependent significant inhibition of STAT3 phosphorylation and STAT3 phosphorylation induced by IL-6.
Down-regulated Cyclin D1, Bcl-2, Mcl-1 and Survivin.
Selectively inhibited the phosphorylation of JAK2, and had no significant effect on JAK1 and JAK3.
Down-regulated Snail and vimentin, and up-regulated E-cadherin.
Caused a dose-dependent increase in the expression of collagen 1 and collagen 3 mRNA in HK2 cells.
Significantly increased the expression of collagen 1 in NHMCs.
Increased collagen 1, collagen 3, TGFβ, CTGF mRNA.
Did not cause significant changes in the above indicators in the SYF cells.
Increased the expression of the epithelial marker E-cadherin and reduced the expression of interstitial markers vimentin and fibronectin.
Significantly reduced the level of Snail protein and had no significant effect on other EMT transcription factors (Slug, Twist1, Zeb1, Zeb2).
Reduced the protein levels of p-Akt, p-mTOR and p-ERK and did not affect the expression of total Akt, mTOR and ERK proteins.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
A549 xenograft tumor model established in female nude mice (BALB/c nude, 4-5-week-old)[1]
Dosage:
1 and 2 mg/kg
Administration:
Intraperitoneal injection (i.p.), every 2 days for a total of 18 days
Result:
Significantly reduced tumor size.
Showed no weight loss and had no noticeable toxicity on the heart, liver, lungs, or kidneys at this concentration.
Reduced the expression of PSTAT3Y705, MCL1, and BCL2 and increased the levels of cleaved PARP1.
Animal Model:
143B cells xenograft tumor model established in male nude mice (BALB/c nude, 6-8-week-old)[2]
Dosage:
5 mg/kg and 10 mg/kg
Administration:
Intraperitoneal injection (i.p.), every 2 days for a total of 20 days
Result:
Significantly reduced tumor weights.
Reduced the numbers of metastatic nodules.
Reduced the levels of phospho-STAT3 and phospho-JAK2.
Increased the proportion of cleaved caspase-3-positive tumor cells.
Animal Model:
S. typhimurium infection model established in female ICR mice (five weeks old, Grade II)[3]
Dosage:
10, 20, and 40 μg dissolved in saline
Administration:
Subcutaneous injection (s.c.), two doses on day 1 and day 15
Result:
Increased the survival rate of mice and reduced bacterial load.
Increased the levels of specific IgG2a (Th1-related antibodies) in OVA and FIST, while the level of IgG1 (Th2-related antibody) did not change significantly.
Promoted the secretion of IFN-γ (a key cytokine for Th1 cells) by spleen cells, but inhibited IL-4 (a marker for Th2 cells) and IL-17A (a marker for Th17 cells).
Upregulated the mRNA expression of the transcription factor T-bet (a key regulatory factor for Th1 cells), while having no significant effect on GATA-3 (Th2) and RORγt (Th17).
Animal Model:
Acetic acid-induced writhing test, formalin test, tail-flick test, hot-plate test, open-field test, rotarod test established in male Swiss Webster mice (25-30 g)[4]
Dosage:
0.062, 0.125, 0.25, 0.5, and 1 mg/kg (i.p.) and 0.625, 1.125, 2.5, 5, and 10mg/kg (p.o.)
Administration:
Intraperitoneal injection (i.p.) and oral administration (p.o.), single dose
Result:
Significantly inhibited the number of contortions in mice in a dose-dependent manner.
Significantly inhibited the licking time during the first 5 minutes after intraplantar injection of formalin.
Significantly increased the reaction time (the withdrawal by a brief vigorous movement) in a dose-dependent manner.
Significantly increased the reaction time (the withdrawal by a brief vigorous movement) in a dose-dependent manner.
Presented significant reaction latencies for 3 hours after administration (1 mg/kg, i.p; 10 mg/kg, p.o).
Did not affect locomotion in mice in open-field test and rotarod test.
Exhibited the potency about 4 times higher than that of morphine.
Animal Model:
Measurement of renal fibrosis model established in wild-type male SvJ/Black Swiss mice (25-30 g) (WT), as well as SvJ/Black Swiss mice heterozygous for the Na+/K+-ATPase-α-1 (referred to as NKA α-1+/−)[5]
Dosage:
0.1 mg/kg
Administration:
Intraperitoneal injection (i.p.), once daily for 4 weeks
Result:
Caused a significant increase in systolic blood pressure in both wild-type mice and NKAα-1+/− mice, but at 4 weeks, the amount of urinary protein excreted by NKAα-1+/− mice was significantly less than that of the wild-type control group.
Resulted in mild to moderate periglomerular and peritubular fibrosis of the renal cortex and the degree of renal fibrosis in NKAα-1+/− mice was lower than that in the wild-type control group at 4 weeks.
Animal Model:
4T1 cells xenograft tumor model established in six week old female BALB/c nude mice (18 22 g)[7][8]
Dosage:
10 or 20 µg/mouse
Administration:
Intraperitoneal injection (i.p.), three times a week for two consecutive weeks.
Result:
Significantly reduced the tumor volume and weight.
Reduced the number of lung metastatic lesions
Observed EMT markers and signaling pathway proteins in tumor tissues consistent with those in the in vitro experiments.
Animal Model:
Cal-27 cells xenograft tumor model and normal or PLK1 over-expressed HNSCC cells induced lung metastasis model established in BALB/c nude mice[9]
Dosage:
4, 8, and 16 mg/kg (xenograft tumor model) and 8 mg/kg (lung metastasis model)
Administration:
Intraperitoneal injection (i.p.), once daily for 30 days
Result:
Significantly inhibited the growth of transplanted tumors and lung metastasis.
Downregulated the expressions of PLK1, CDC25c and Ki67 in tumor tissues and overexpression of PLK1 can completely reverse the anti-tumor effect of TBG.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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