Bufalin as a potent inducer of differentiation of human myeloid leukemia cells

Zhang, Lisha; Nakaya, Kazuyasu; Yoshida, Takemi; Kuroiwa, Yukio

doi:10.1016/0006-291x(91)90162-z

Cited by 66 publications

(44 citation statements)

References 16 publications

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“…Treatment of K562 cells with other cardiotonic steroids, such as cinobufagin, ouabain and digitoxigenin, at the concentration of 10 nM for four days resulted in weak or no effect on the cells. These findings suggest that bufalin might have potentiality as a new agent in the differentiation therapy for human myelogenous leukemia (Zhang et al, 1991;Masuda et al, 1995;Watabe et al, 1998;Kawazoe et al, 1999).…”

Section: Leukemiamentioning

confidence: 80%

Bufalin, a Traditional Oriental Medicine, Induces Apoptosis in Human Cancer Cells

Takai

Kira²,

Ishii³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Leukemiamentioning

confidence: 80%

Bufalin, a Traditional Oriental Medicine, Induces Apoptosis in Human Cancer Cells

Takai

Kira²,

Ishii³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…The Na + ,K + -ATPase seems likely to be an early target of bufalin because the plasma membrane is impermeable to bufalin (Numazawa et al, 1994), and the activity of the Na + ,K + -ATPase in various lines of tumor cells is strongly inhibited by bufalin (Zhang et al, 1991). Although the detailed mechanism is unknown, a signal might be transmitted from Na + ,K + -ATPase to Ras.…”

Section: Of Results From Three Independent Experimentsmentioning

confidence: 99%

“…Chemotherapeutic agents, such as cisplatin (Kaufmann, 1989;Barry et al, 1990) and taxol (Bhalla et al, 1993), and inhibitors of topoisomerases I and II, such as camptothecin and etoposide (Kaufmann, 1989;Walker et al, 1991;Onishi et al, 1993), induce apoptosis. We have shown that bufalin, a component of the traditional Chinese medicine chan'su, acts as a potent di erentiation-and apoptosis-inducing agent in various lines of tumor cells (Zhang et al, 1991;Jing et al, 1994;Masuda et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Tiam1 is involved in the regulation of bufalin-induced apoptosis in human leukemia cells

et al. 1999

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Bufalin, a component of the Chinese medicine chan'su, induces apoptosis in various lines of human tumor cells, such as leukemia HL60 and U937 cells, by altering the expression of apoptosis-related genes, for example, bcl-2 and c-myc. In this study, we characterized a gene that is involved in bufalin-induced apoptosis by the di erential display (DD) technique. The partial nucleotide sequence of one of the di erentially expressed clones obtained after treatment with bufalin was identical to that of the human gene for Tiam1. When U937 cells were treated with 10 77 M bufalin, expression of both Tiam1 mRNA and the protein was induced 1 h after the start of the treatment. The increase of Tiam1 mRNA was transient but the level of Tiam1 protein continued to increase at least for 6 h. In addition, the activities of Rac1 and p21-activated kinase (PAK) were also stimulated by bufalin treatment. To evaluate the role of Tiam1 in the apoptotic process, we examined the e ects of the expression of sense and antisense RNA for Tiam1 in U937 cells. Apoptosis was strongly induced by bufalin in cells that expressed sense RNA for Tiam1 as compared to apoptosis in control cells treated with bufalin only. Cells expressing antisense RNA for Tiam1 were signi®cantly more resistant than the control bufalin-treated cells to induction of DNA fragmentation in response to bufalin. Moreover, sense transformants had elevated activities of PAK and c-Jun NH 2 -terminal kinase (JNK). These results suggest that Tiam1 might play a critical role in bufalin-induced apoptosis through the activation of Rac1, PAK, and JNK pathway.

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“…Bufalin is a biologically active component of the Traditional Chinese Medicine Chan'Su, which has the potential to induce differentiation and apoptosis in a wide spectrum of tumor cells (26,27). Numerous studies have investigated the potential molecular mechanism of the anti-tumor activity of bufalin, indicating that the mitochondria-mediated signaling pathway has a pivotal role in the process of apoptosis induced by bufalin.…”

Section: Discussionmentioning

confidence: 99%

Bufalin induces apoptosis in the U-2OS human osteosarcoma cell line via triggering the mitochondrial pathway

Chen¹,

Li²,

Li³

et al. 2015

Molecular Medicine Reports

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Abstract. Bufalin has been shown to induce apoptosis in osteosarcoma cells; however, the underlying mechanism has not been elucidated. The purpose of the present study was to investigate whether mitochondria-mediated signaling pathways trigger the process of apoptosis in the U-2OS osteosarcoma cell line. Bufalin inhibited the proliferation and induced apoptosis in U-2OS cells in a time-and dose-dependent manner. Bufalin-induced apoptosis was accompanied with a significant reduction of the mitochondrial membrane potential, release of mitochondrial cytochrome c into the cytosol, activation of caspase-3, caspase-9 and poly(adenosine diphosphate ribose) polymerase, as well as downregulation of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein. Cyclosporin A, a specific inhibitor of the mitochondrial permeability transition pore, attenuated bufalin-induced apoptosis. In conclusion, the present study revealed that bufalin induced apoptosis in the U-2OS human osteosarcoma cell line via triggering of the mitochondrial pathway.

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Bufalin as a potent inducer of differentiation of human myeloid leukemia cells

Cited by 66 publications

References 16 publications

Bufalin, a Traditional Oriental Medicine, Induces Apoptosis in Human Cancer Cells

Bufalin, a Traditional Oriental Medicine, Induces Apoptosis in Human Cancer Cells

Tiam1 is involved in the regulation of bufalin-induced apoptosis in human leukemia cells

Bufalin induces apoptosis in the U-2OS human osteosarcoma cell line via triggering the mitochondrial pathway

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