Title:L-Tetrahydropalmatine Induces Apoptosis in EU-4 Leukemia Cells by Down-Regulating X-Linked Inhibitor of Apoptosis Protein and Increases the Sensitivity Towards Doxorubicin
Volume: 17
Issue: 3
Author(s): S. Li, D. Chen, R. Pei *, Y. Lu*, P. Zhang, J. Ma, X. Liu, X. Du, K. Sha, L. Chen, J. Cao, X. Zhuang, J. Wu, L. Lin, Z. Fan, P. Ye, S. Tang, B. Zhang, X. Shi and K. Li
Affiliation:
- Department of Hematology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040,China
- Department of Hematology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040,China
Keywords:
L-Tetrahydropalmatine, isoquinoline alkaloid, leukemia, EU-4 cells, XIAP, MDM2.
Abstract: Background: L-Tetrahydropalmatine (L-THP) is a tetra-hydro protoberberine
isoquinoline alkaloid. The phyto-compounds bearing isoquinoline alkaloids have been
reported to show a potential effect against a number of human cancers cell lines
including leukemia. We hypothesized that L-THP, being an isoquinoline alkaloid, could
be a potential molecule against acute lymphoblastic leukemia (ALL), in this study, we
evaluate L-THP against p53 deficient leukemia EU-4 cell lines in vitro.
Methods: For the study, p53 null leukemia EU-4 cells were used and treated with LTHP.
The extent of apoptosis and viability of cells were determined. Expression of
apoptosis related proteins such as XIAP and MDM2 was done by western blot and PCR
studies. The expression of MDM2 and XIAP was knocked down by small interfering RNA
(siRNA).
Results: Outcomes of the study suggested that L-THP caused p53-indipendent
apoptosis mediated by XIAP in EU-4 cells. The treatment of L-THP caused a decrease in
the levels of XIAP protein with increasing dose and time. L-THP caused down-regulation
of XIAP protein via inhibiting the expression of MDM2 and involving proteasomedependent
pathway. Also, the outcomes of experiments suggested increased sensitivity
of leukemia cells towards doxorubicin due to the inhibition of XIAP by L-THP or by
siRNA.
Conclusion: Findings of the study confirm that L-THP resulted in p53 independent
apoptosis via down-regulating XIAP protein by inhibiting MDM2 associated with
proteasome-dependent pathway and increased sensitivity of EU-4 cells against
doxorubicin. L-THP caused activation of caspase and resulted in apoptosis, L-THP may
be a novel molecule for inducing apoptosis specifically in p53 null leukemia EU-4 cells.
