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Curcumin analogue, A13, exhibits anti-leukemia effect via inhibiting STAT3
Qiaoyou Weng1,2, Luqing Ren1, Lu Guo1
1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Abstract:
Abnormal activation of signal transducer and activator of transcription 3 (STAT3) was reported in some leukemia, and inhibition of STAT3 can be the strategy for the leukemia treatment in clinic. In this study, we tested the anti-tumor effect of compound A13, a water-soluble analogue of curcumin, in vitro and in vivo. Herein, we show that A13 was able to reduce the viability of mastocytoma (P815 cells) and reticulum cell sarcoma (A20 cells) as measured by MTS assay. This effect was accompanied by a marked increase in the proportion of apoptotic cells as measured by flow cytometry. Furthermore, Western blot analysis suggested that the anti-leukemia effect of A13 was realized via STAT3 inhibition. In addition, systemic treatment with A13 in the A20-bearing mice for 60 days resulted in a significant improvement of survival rate and marked reduction of liver metastasis. In summary, our data show that the A13 treatment could effectively be applied to acute leukemia via inhibiting STAT3 signaling pathway.
Insights
Compound A13, a curcumin derivative, effectively combats leukemia by inhibiting the STAT3 pathway. This novel treatment reduces cancer cell viability and improves survival rates in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Abnormal Signal Transducer and Activator of Transcription 3 (STAT3) activation is implicated in various leukemias.
- STAT3 inhibition presents a potential therapeutic strategy for leukemia treatment.
Purpose of the Study:
- To evaluate the anti-tumor efficacy of compound A13, a water-soluble curcumin analogue.
- To investigate the mechanism of A13's anti-leukemic effect, focusing on STAT3 signaling.
Main Methods:
- In vitro studies using MTS assay and flow cytometry on mastocytoma (P815) and reticulum cell sarcoma (A20) cells.
- Western blot analysis to assess STAT3 inhibition.
- In vivo studies involving A20-bearing mice treated with A13.
Main Results:
- A13 significantly reduced the viability of P815 and A20 cells.
- A13 induced apoptosis in leukemia cells.
- A13 treatment led to decreased STAT3 activation.
- In vivo, A13 improved survival rates and reduced liver metastasis in A20-bearing mice.
Conclusions:
- Compound A13 demonstrates potent anti-leukemic effects.
- A13 exerts its anti-cancer activity through the inhibition of the STAT3 signaling pathway.
- A13 shows promise as a therapeutic agent for acute leukemia.
