KEY TAKEAWAYS
- The study aimed to investigate the impact of DHA on Mcl-1 expression and its role in sensitizing T-ALL cells to ABT-737.
- Researchers observed that DHA exhibits anti-tumor effects in human ALL cells by impeding cell survival and growth.
Up-regulation of anti-apoptotic proteins, particularly Mcl-1, plays a pivotal role in the development of primary and secondary resistance of tumor cells to ABT-737, a Bcl-2 inhibitor. Combining Bcl-2 inhibitors with Mcl-1 inhibitors has emerged as a promising therapeutic strategy to address this challenge. Roya Nazmabadi and her team aimed to investigate the impact of dihydroartemisinin (DHA) on Mcl-1 expression and its potential in sensitizing T-cell Acute Lymphoblastic Leukemia (T-ALL) cells to ABT-737.
They performed an inclusive analysis, employing cell proliferation and MTT assays to evaluate cell growth and survival. The mRNA levels of key regulatory genes, including Bcl-2, Mcl-1, Bax, and P21, were examined using qRT-PCR. Apoptosis was assessed through Hoechst 33342 staining and caspase-3 activity assay.
The study showed that the combination treatment of DHA and ABT-737 resulted in a significant reduction in the IC50 value, demonstrating a synergistic effect in decreasing cell survival compared to the individual treatments with DHA or ABT-737 alone. Specifically, ABT-737 was found to enhance Mcl-1 mRNA expression. DHA exhibited down-regulation of both Bcl-2 and Mcl-1 expression while concurrently enhancing the expression of P21 and Bax.
DHA demonstrated an augmentation of apoptosis induced by ABT-737 in MOLT-4 and MOLT-17 cell lines. These findings collectively highlight the effectiveness of the combined treatment in overcoming drug resistance and promoting apoptotic mechanisms in T-ALL cells.
The study concluded that DHA exhibits significant anti-tumor activities in human ALL cells by inhibiting cell survival and growth. Furthermore, DHA enhanced the apoptotic effect of ABT-737 through the inhibition of Mcl-1 expression.
Source: https://pubmed.ncbi.nlm.nih.gov/38285800/
Nazmabadi R, Pooladi M, Amri J, et al.” Dihydroartemisinin Enhances the Therapeutic Efficacy of BH3 Mimetic Inhibitor in Acute Lymphoblastic Leukemia Cells via Inhibition of Mcl-1. Asian Pac J Cancer Prev. 2024 Jan 1;25(1):325-332. doi: 10.31557/APJCP.2024.25.1.325. PMID: 38285800.
