A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid

Kasibhatla, Shailaja; Jessen, Katayoun A.; Maliartchouk, Sergei; Wang, Jean Yu; English, Nicole M.; Drewe, John; Qiu, Ling; Archer, Shannon P.; Ponce, Anthony E.; Sirisoma, Nilantha; Jiang, Songchun; Zhang, Hanzhong; Gehlsen, Kurt R.; Cai, Sui Xiong; Green, Douglas R.; Tseng, Ben

doi:10.1073/pnas.0406731102

Cited by 200 publications

(173 citation statements)

References 26 publications

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“…This result suggests the presence of other targets aside from p53. In addition, a recent study from Kasibhatla et al (25) and Pandey et al (34) showed that transferrin receptor (CD71), an iron-transport protein that was highly expressed in tumor cell membrane, was the ligand of GA, leading to mitochondria-dependent and mitochondriaindependent apoptosis pathway activation by GA. Therefore, we examine the involvement of CD71 using siRNA to knock down CD71.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, GA induced cancer cell G 2 -M phase arrest and repressed telomerase reverse transcriptase (23,24). Recently, Kasibhatla et al showed that transferrin receptor (TfR or CD71) is the target protein of GA (25). All studies reported to date show that GA is a potent anticancer agent with diverse molecular targets through different mechanisms (26).…”

Section: Introductionmentioning

confidence: 99%

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Gambogic acid mediates apoptosis as a p53 inducer through down-regulation of mdm2 in wild-type p53-expressing cancer cells

Wang

Rao

et al. 2008

Molecular Cancer Therapeutics

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gambogic acid mediates apoptosis as a p53 inducer through down-regulation of mdm2 in wild-type p53-expressing cancer cells

Wang

Rao

et al. 2008

Molecular Cancer Therapeutics

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“…The resin has been used in traditional Chinese medicine for the treatment of cancers (15). It has potent anticancer activity because of its activation of the apoptotic pathways in cancerous cells (16)(17)(18)(19). Recently, it has been reported that GA triggers apoptosis upon binding to the transferrin receptor (20).…”

mentioning

confidence: 99%

Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death

Jang¹,

Okada²,

Sayeed³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

131

106

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Nerve growth factor (NGF) binds to TrkA receptor and triggers activation of numerous signaling cascades, which play critical roles in neuronal plasticity, survival, and neurite outgrowth. To mimic NGF functions pharmacologically, we developed a high-throughput screening assay to identify small-molecule agonists for TrkA receptor. The most potent compound, gambogic amide, selectively binds to TrkA, but not TrkB or TrkC, and robustly induces its tyrosine phosphorylation and downstream signaling activation, including Akt and MAPKs. Further, it strongly prevents glutamate-induced neuronal cell death and provokes prominent neurite outgrowth in PC12 cells. Gambogic amide specifically interacts with the cytoplasmic juxtamembrane domain of TrkA receptor and triggers its dimerization. Administration of this molecule in mice substantially diminishes kainic acid-triggered neuronal cell death and decreases infarct volume in the transient middle cerebral artery occlusion model of stroke. Thus, gambogic amide might not only establish a powerful platform for dissection of the physiological roles of NGF and TrkA receptor but also provide effective treatments for neurodegenerative diseases and stroke.neurotrophic effect ͉ nerve growth factor ͉ ligand ͉ receptor dimerization

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“…It is known that caspase-8 and caspase-9 are activated by the death receptor signaling pathway and the mitochondrial signaling pathway during apoptosis in order, whereas caspase-3 is a common effector of both signaling pathways. 33,34 Therefore, we speculate that the LCL-HHT-H-PEG might induce MM CSC apoptosis via mitochondrial apoptotic pathway. This was because the LCL-HHT-H-PEG formulation enhanced the expression of the initiator caspase-9 and the executioner caspase-3, which led to MM cell apoptosis.…”

Section: Lcl-hht-h-peg Induces the Apoptosis Of MM Cells In Vivo And mentioning

confidence: 99%

PEGylated long-circulating liposomes deliver homoharringtonine to suppress multiple myeloma cancer stem cells

Shi

Xiong

et al. 2017

Exp Biol Med (Maywood)

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Multiple myeloma (MM) remains largely incurable until now. One of the main reasons is that there are cancer stem cells (CSCs) in MM, which are responsible for MM's drug resistance and relapse. In this study, we wanted to extend our previous investigation 22 that whether we developed the LCL-HHT-H-PEG formulation have an inhibitory effect on MM CD138 AbstractThe goal of this investigation was to evaluate the inhibiting effect of high proportion polyethyleneglycol of long-circulating homoharringtonine liposomes on RPMI8226 multiple myeloma cancer stem cells. The CD138 À CD34À multiple myeloma cancer stem cells isolated from RPMI8226 cell line using magnetic activated cell sorting system were, respectively, incubated with the optimized formulation of polyethyleneglycol of long-circulating homoharringtonine liposomes and the homoharringtonine in vitro, and the multiple myeloma cancer stem cell proliferation, colony formation, and cell cycle were analyzed. The inhibition of the multiple myeloma CD138 À CD34 À cancer stem cell growth was investigated in non--obese-diabetic/severe-combined-immunodeficiency mice that were implanted with multiple myeloma RPMI 8226 cancer stem cells and treated with the LCL-HHT-H-PEG. The results showed that the polyethyleneglycol of long-circulating homoharringtonine liposomes significantly inhibited MM cancer stem cell proliferation, colony formation, and induced cancer stem cell apoptosis in vitro as well as MM cancer stem cell growth in non-obesediabetic/severe-combined-immunodeficiency mice compared with the homoharringtonine. In addition, the mouse bone mineral density and the red blood cell count were significantly increased in polyethyleneglycol of long-circulating homoharringtonine liposomes group. In conclusion, the data demonstrated that the developed polyethyleneglycol of long-circulating homoharringtonine liposomes formulation may serve as an efficient therapeutic drug for suppressing CD138 À CD34À multiple myeloma cancer stem cell growth by inducing cancer stem cell apoptosis in non-obese-diabetic/severe-combined-immunodeficiency mouse model.

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A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid

Cited by 200 publications

References 26 publications

Gambogic acid mediates apoptosis as a p53 inducer through down-regulation of mdm2 in wild-type p53-expressing cancer cells

Gambogic acid mediates apoptosis as a p53 inducer through down-regulation of mdm2 in wild-type p53-expressing cancer cells

Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death

PEGylated long-circulating liposomes deliver homoharringtonine to suppress multiple myeloma cancer stem cells

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