β‐Hydroxyisovalerylshikonin Is a Novel and Potent Inhibitor of Protein Tyrosine Kinases

Hashimoto, Sachiko; Xu, Ying; Masuda, Yutaka; Aiuchi, Toshihiro; Uehara, Yoshimasa; Shibuya, Masabumi; Yamori, Takao; Nakaya, Kazuyasu

doi:10.1111/j.1349-7006.2002.tb01341.x

Cited by 37 publications

(29 citation statements)

References 28 publications

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“…It has been reported that ␤-HIVS inhibits the activity of several tyrosine kinases, such as v-Src and a receptor for EGF in vitro (13), and that it exerts its apoptosis-inducing activity via the inhibition of tyrosine kinases (14). Thus, it is possible that tyrosine kinases might be direct targets of ␤-HIVS in the induction of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Most of the PTK inhibitors reported to date, including STI571, ZD1839, SU5416, and PD173074, have chemical structures that resemble the structure of ATP and compete with ATP for binding to the ATP binding site in the catalytic domain of the PTKs, with resultant inhibition of enzymatic activities. By contrast to these ATP-competitive inhibitors of PTK, the shikonin derivative ␤-hydroxyisovalerylshikonin (␤-HIVS), isolated from the plant Lithospermum radix, inhibits the activity of v-Src in an ATP-non-competitive manner (13). This feature of ␤-HIVS is very useful for the inhibition of PTK activity in vivo because ␤-HIVS does not need to compete with ATP in the intracellular environment.…”

Section: From the Laboratory Of Biological Chemistry School Of Pharmmentioning

confidence: 99%

“…Effect of Inhibitors of Tyrosine Kinase on the Expression of TRAP1-Our previous study showed that tyrosine kinases might be one of direct targets of ␤-HIVS in the induction of apoptosis (13). To study the mechanism of down-regulation of the expression of TRAP1 by ␤-HIVS, we investigated the effects of inhibition of tyrosine kinases on the expression of TRAP1.…”

Section: Expression Of Bcl-2 Inhibits Both the Release Of Cytochrome mentioning

confidence: 99%

“…In a previous study, we examined the effects of ␤-HIVS on the induction of cell death in 37 lines of cancer cells derived from human solid tumors, and we showed that ␤-HIVS induced cell death most efficiently in human lung cancer DMS114 cells (13). Fig.…”

Section: Suppression Of Expression Of the Gene For Trap1 In Humanmentioning

confidence: 99%

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Involvement of Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) in Apoptosis Induced by β-Hydroxyisovalerylshikonin

Masuda

Shima

Aiuchi

et al. 2004

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: From the Laboratory Of Biological Chemistry School Of Pharmmentioning

confidence: 99%

Section: Expression Of Bcl-2 Inhibits Both the Release Of Cytochrome mentioning

confidence: 99%

Section: Suppression Of Expression Of the Gene For Trap1 In Humanmentioning

confidence: 99%

See 2 more Smart Citations

Involvement of Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) in Apoptosis Induced by β-Hydroxyisovalerylshikonin

Masuda

Shima

Aiuchi

et al. 2004

Journal of Biological Chemistry

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135

104

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“…These results suggest that b-HIVS might inhibit Bcr-Abl or other tyrosine protein kinases. Indeed, b-HIVS inhibits the activity of several tyrosine kinases, such as v-Src and a receptor for EGF in vitro (Hashimoto et al, 2002). Thus, it is likely that tyrosine kinases are possible targets of b-HIVS.…”

Section: Discussionmentioning

confidence: 99%

β-Hydroxyisovalerylshikonin induces apoptosis in human leukemia cells by inhibiting the activity of a polo-like kinase 1 (PLK1)

et al. 2003

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b-Hydroxyisovalerylshikonin (b-HIVS), which was isolated from the plant, Lithospermum radix, induces apoptosis in various lines of human tumor cells. To identify genes involved in b-HIVS-induced apoptotic process, we performed cDNA array analysis and found that b-HIVS suppresses the expression of the gene for a polo-like kinase 1 (PLK1) that is involved in control of the cell cycle. When U937 and HL60 cells were treated with 10 À6 m b-HIVS for 0.5 h, both the amount of PLK1 itself and the kinase activity of this enzyme were decreased. By contrast, Bcr-Abl-positive K562 cells were resistant to the induction of apoptosis by b-HIVS and this compound did not suppress the kinase activity of PLK1 in these cells. However, simultaneous treatment of K562 cells with both b-HIVS and STI571, which selectively inhibits the protein tyrosine kinase (PTK) activity of Bcr-Abl, strongly induced apoptosis. Moreover, b-HIVS increased the inhibitory effect of STI571 on PTK activity. Treatment of K562 cells with antisense oligodeoxynucleotides (ODNs) specific for PLK1 sensitized these cells to the b-HIVS-induced fragmentation of DNA. These results suggest that suppression of the activity of PLK1 via inhibition of tyrosine kinase activity by b-HIVS might play a critical role in the induction of apoptosis.

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et al. 2010

Burger's Medicinal Chemistry and Drug Discovery

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β‐Hydroxyisovalerylshikonin Is a Novel and Potent Inhibitor of Protein Tyrosine Kinases

Cited by 37 publications

References 28 publications

Involvement of Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) in Apoptosis Induced by β-Hydroxyisovalerylshikonin

Involvement of Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) in Apoptosis Induced by β-Hydroxyisovalerylshikonin

β-Hydroxyisovalerylshikonin induces apoptosis in human leukemia cells by inhibiting the activity of a polo-like kinase 1 (PLK1)

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