Celastrol and an EGCG pro-drug exhibit potent chemosensitizing activity in human leukemia cells.
Chemotherapy remains the staple of treatment for many types of leukemia. Despite the positive impact on extending overall survival in patients with hematological malignancies, new treatment strategies are needed to reduce the nonspecific toxicity and improve the efficacy of treatment. Celastrol, derived from the 'Thunder God Vine' and Pro-EGCG, a pre-drug version of green tea polyphenol EGCG have shown potent biological activity in vitro and in vivo. Whether these natural products augment the efficacy of conventional chemotherapy in the treatment of leukemia cells has yet to be demonstrated. Here we demonstrate that these natural products could sensitize the effect of chemotherapy in both K-562 and Jurkat T human leukemia cells. Accordingly, this potent biological activity was associated with increased levels of leukemia cell killing, caspase 3 activation, and poly(ADP-ribose) polymerase cleavage. Furthermore, the higher levels of apoptotic indices were associated with decreased levels of Bcr-Abl oncoprotein in K-562 cells. Taken together, our findings present a compelling rationale for the development of combination strategies using natural products in the treatment of hematological malignancies.
Davenport
Andrew
A
The Prevention Program, Barbara Ann Karmanos Cancer Institute, Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA.
Frezza
Michael
M
Shen
Min
M
Ge
Yubin
Y
Huo
Congde
C
Chan
Tak Hang
TH
Dou
Q Ping
QP
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects*; D003561:Cytarabine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D003630:Daunorubicin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D011355:Prodrugs; D014315:Triterpenes; D003561:Cytarabine; D002392:Catechin; C045651:epigallocatechin gallate; D016044:Fusion Proteins, bcr-abl; C050414:celastrol; D003630:Daunorubicin