Dihydroartemisinin Induced Apoptosis and Synergized With Chemotherapy in Pleural Effusion Lymphoma Cells
Issued Date
2023-03-01
Resource Type
ISSN
02507005
eISSN
17917530
Scopus ID
2-s2.0-85149153602
Pubmed ID
36854534
Journal Title
Anticancer Research
Volume
43
Issue
3
Start Page
1139
End Page
1148
Rights Holder(s)
SCOPUS
Bibliographic Citation
Anticancer Research Vol.43 No.3 (2023) , 1139-1148
Suggested Citation
Phikulsod P., Kariya R., Panaampon J., Okada S. Dihydroartemisinin Induced Apoptosis and Synergized With Chemotherapy in Pleural Effusion Lymphoma Cells. Anticancer Research Vol.43 No.3 (2023) , 1139-1148. 1148. doi:10.21873/anticanres.16259 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/81642
Title
Dihydroartemisinin Induced Apoptosis and Synergized With Chemotherapy in Pleural Effusion Lymphoma Cells
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
Background/Aim: Primary effusion lymphoma (PEL) is a rare aggressive B-cell lymphoma associated with HHV-8. With a median survival of fewer than six months, the prognosis of the disease with current standard therapies is usually dismal. Dihydroartemisinin (DHA) is a derivative of artemisinin, originally designed as an antimalarial drug. Several studies have shown that this compound also demonstrates anti-cancer activity in various types of cancer, including hematologic malignancies. Materials and Methods: Anti-proliferation activity of DHA on 5 PEL cell lines was assessed by MTT assay. Cell cycle arrest was determined by propidium iodide staining and flow cytometry analysis. DHA-induced PEL apoptosis was shown by annexin V/PI staining and western blotting for cleaved caspases 3, 8, and 9. An inhibitory effect on PEL growth was evaluated in a PEL-xenograft mouse model. A synergistic effect of DHA and doxorubicin combination treatment was shown in vitro. Results: DHA showed anti-proliferative activity on PEL and induced caspase-dependent apoptosis in a time- and dose-dependent manner. DHA-induced cell death appeared to be triggered by increased levels of reactive oxygen species (ROS). N-acetylcysteine treatment inhibited DHA-induced ROS elevation and suppressed expression of cleaved caspases leading to significantly reduced PEL apoptosis. DHA treatment also demonstrated an inhibitory effect on PEL cell growth in an in-vivo xenograft model. Moreover, we found that a combination treatment of DHA and doxorubicin, the standard chemotherapy drug for PEL, demonstrated a synergistic effect on PEL cell lines. Conclusion: DHA is a potentially effective candidate drug for PEL treatment.