title: Flavokawain B inhibits the growth of acute lymphoblastic leukemia cells via p53 and caspase-dependent mechanisms.
abstract: The development of novel chemotherapeutic drugs is needed for the treatment of patients with acute lymphoblastic leukemia (ALL). In this study, the anti-leukemic effect and the potential molecular mechanisms of action of flavokawain B on ALL were investigated. Flavokawain B was found to significantly inhibit the cellular proliferation of B-ALL and T-ALL cell lines in a dose-dependent manner. It also induced cellular apoptosis by increasing the expression of p53, Bax and Puma, and activating the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP). Furthermore, the enhancement of p53-dependent apoptosis by flavokawain B could be rescued by pifithrin-α, a pharmacological inhibitor of p53 transcriptional activity. Moreover, the proliferation of leukemia blast cells from 16 patients with ALL was inhibited by flavokawain B, and tumor growth in xenograft mice was also suppressed by this drug. In conclusion, our results demonstrate the therapeutic potential of flavokawain B for the treatment of ALL.
authors: a Department of Pediatrics , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors: Yan-Lai
authors: YL
authors: Tang
authors: a Department of Pediatrics , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors: Li-Bin
authors: LB
authors: Huang
authors: b Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine , Guangzhou , China.
authors: Yun
authors: Y
authors: Tian
authors: a Department of Pediatrics , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors: Li-Na
authors: LN
authors: Wang
authors: a Department of Pediatrics , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors: Xiao-Li
authors: XL
authors: Zhang
authors: a Department of Pediatrics , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors: Zhi-Yong
authors: ZY
authors: Ke
authors: b Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine , Guangzhou , China.
authors: Wu-Guo
authors: WG
authors: Deng
authors: a Department of Pediatrics , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors: Xue-Qun
authors: XQ
authors: Luo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D005419:Flavonoids; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C452039:flavokawain B; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D020169:Caspases
keywords: Flavokawain B; acute lymphoblastic leukemia (ALL); apoptosis; p53; proliferation