Baicalin Induces Apoptosis in Leukemia HL-60/ADR Cells via Possible Down-regulation of the PI3K/Akt Signaling Pathway

Zheng, Jing; Hu, Jianda; Chen, Yingyu; Chen, Bu-Yuan; Huang, Yi; Zheng, Zhi Hong; Liu, Tingbo

doi:10.7314/apjcp.2012.13.4.1119

Cited by 29 publications

(19 citation statements)

References 20 publications

(18 reference statements)

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“…However, the appearance of the hypodiploid peak in the cell cycle distribution demonstrated that apoptosis also contributed to cell proliferation inhibition by baicalin. Furthermore, the cell morphological changes observed and Annexin V/PI staining results further confirmed this, and are concordant with preceding reports (3,4,6,8).…”

Section: Discussionsupporting

confidence: 81%

“…supplemented with 10% newborn calf serum (Gibco; Thermo Fisher Scientific, Inc.), 100 IU/ml penicillin and 100 IU/ml streptomycin in a 5% CO 2 atmosphere at 37˚C. Logarithmically growing HL-60 cells were seeded on a 96-well plate at a density of 1x10 4 cells/well in 50 µl of medium in triplicate, and then different concentrations of baicalin (5, 10, 20, 40 and 80 µg/ml) in 50 µl were added. Cells treated with 0.1% (v/v) DMSO were used as the control.…”

Section: The Downregulation Of C-myc and Its Target Gene Htert Is Assmentioning

confidence: 99%

“…1A), a Chinese traditional medicinal herb used as an anti-inflammatory (1), antibacterial, anxiolytic and hepatoprotective drug (2). Accumulating evidence has demonstrated that baicalin exhibits potent antitumor properties by suppressing cell growth, arresting the cell cycle and inducing differentiation or apoptosis in leukemia cell lines (3,4), without affecting primary, or normal cells (5), which raises the possibility of using baicalin to treat patients with leukemia. Baicalin has been documented to induce apoptosis of the Jurkat T-cell acute lymphoblastic leukemia (T-ALL) cell line via the mitochondrial pathway, which involves marginal generation of intracellular reactive oxygen species (ROS), an increase in the cytosolic fractions of cytochrome c and disruption of the mitochondrial transmembrane potential (∆Ψm) (6).…”

Section: Introductionmentioning

confidence: 99%

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The downregulation of c‑Myc and its target gene hTERT is associated with the antiproliferative effects of baicalin on HL‑60 cells

et al. 2017

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Abstract. Baicalin is a flavonoid compound isolated fromScutellaria baicalensis, a Chinese traditional medicinal herb, and is used as an anti-inflammatory, antibacterial, anxiolytic and hepatoprotective drug. Accumulating evidence has demonstrated that baicalin exhibits potent antitumor properties by suppressing cell growth, arresting cell cycle progression and inducing differentiation or apoptosis in leukemia cell lines. However, whether or not the extrinsic pathway is involved in baicalin-induced apoptosis of leukemia cells and the mechanisms underlying the antitumor activity of baicalin remain unclear. In the present study, the effect of baicalin on the expression of caspase-8, Fas cell surface death receptor (Fas) and Fas ligand in HL-60 cells was assessed, and it was demonstrated that the Fas-mediated extrinsic pathway was also involved in baicalin-triggered cell apoptosis, in addition to the intrinsic pathway. Furthermore, baicalin was able to inhibit the proliferation of HL-60 cells by arresting the cell cycle at the G 0 /G 1 phase, and by down-regulating Myc proto-oncogene protein (c-Myc) along with its target gene, human telomerase reverse transcriptase. In summary, the results of the present study demonstrated that baicalin was able to inhibit the growth of HL-60 cells through blockade of the G 0 /G 1 phase of the cell cycle, and significantly induce the apoptosis of cells by activating the intrinsic and extrinsic pathways. The inhibition of HL-60 cell growth was also demonstrated to be mediated by telomerase inhibition through suppression of c-Myc. The results of the present study highlight the possibility of baicalin as a promising regimen for the treatment of AML.

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Section: Discussionsupporting

confidence: 81%

Section: The Downregulation Of C-myc and Its Target Gene Htert Is Assmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The downregulation of c‑Myc and its target gene hTERT is associated with the antiproliferative effects of baicalin on HL‑60 cells

et al. 2017

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“…When exposed to certain stimuli, the T308 and S473 sites of Akt could be phosphorylated, which finally regulates cell apoptosis/survival. It has been reported that emodin could inhibit the activation of Akt and promote apoptosis of leukemia HL-60 cells (25). Olsen et al also showed that emodin can inhibit the activity of Akt in cervical cancer cells (26).…”

Section: Discussionmentioning

confidence: 99%

Antitumor and apoptosis-promoting properties of emodin, an anthraquinone derivative from Rheum officinale Baill, against pancreatic cancer in mice via inhibition of Akt activation

Wei

Chen²,

Ni³

et al. 2011

Int J Oncol

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Abstract. Pancreatic adenocarcinoma is one of the most common malignancies worldwide. Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. However, gemcitabine can induce activation of Akt and nuclear factor-κB (NF-κB), which is associated with its chemoresistance. It has been reported that gemcitabine combination therapies result in improved survival outcomes in pancreatic cancer. Therefore, agents that can either enhance the effects of gemcitabine or overcome chemoresistance to the drug are needed for the treatment of pancreatic cancer. Emodin is an active component of Chinese medicinal herbs and can inhibit the activation of Akt and NF-κB. In this study, we investigated whether emodin could enhance the anticancer effect of gemcitabine on pancreatic cancer in vivo. We demonstrated that treatment of gemcitabine combined with emodin efficiently suppressed tumor growth in mice inoculated with pancreatic tumor cells. This treatment paradigm promoted apoptotic cell death and mitochondrial fragmentation. Furthermore, it reduced phosphorylated-Akt (p-Akt) level, NF-κB activation and Bcl-2/Bax ratio, increased caspase-9 and -3 activation, Cytochrome C (CytC) release occurred in combination therapy. Collectively, emodin enhanced the activity of gemcitabine in tumor growth suppression via inhibition of Akt and NF-κB activation, thus promoting the mitochondrial-dependent apoptotic pathway. Therefore, our findings may provide new insights into understanding the pharmacological regulation of emodin on gemcitabine-mediated proapoptosis in pancreatic cancer and may aid in the design of new therapeutic strategies for the intervention of human pancreatic cancers.

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“…For example, ligation of surface GRP78 by α2-M* activates MAPK and Akt-dependent signaling and promotes cellular proliferation (Misra et al, 2006), while ligation of surface GRP78 with antibodies against the C-terminal domain of GRP78 result in suppression of cell growth and induction of apoptosis (Misra et al, 2009;Misra and Pizzo, 2010a;Misra and Pizzo, 2010b). Studies have actually shown that the PI3K/Akt signaling plays a significant role in the promotion of tumor cell proliferation and colon tumorigenesis (Zheng et al, 2012). Activation of Akt can stabilize β-catenin by inactivation of GSK-3β or directly induce β-catenin phosphorylation, implicated in cell cycle regulation (Pandurangan, 2013).…”

Section: Discussionmentioning

confidence: 99%

GRP78 Secreted by Colon Cancer Cells Facilitates Cell Proliferation via PI3K/Akt Signaling

Fu¹,

Yang²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Glucose regulated protein 78 (GRP78) is usually recognized as a chaperone in the endoplasmic reticulum. However, increasing evidence indicates that GRP78 can be translocated to the cell surface, acting as a signaling receptor for a variety of ligands. Since little is known about the secretion of GRP78 and its role in the progression of colon cancer we here focused on GRP78 from colon cancer cells, and purified GRP78 protein mimicking the secreted GRP78 was able to utilize cell surface GRP78 as its receptor, activating downstream PI3K/Akt and Wnt/β-catenin signaling and promote colon cancer cell proliferation. Our study revealed a new mode of action of autocrine GRP78 in cancer progression: secreted GRP78 binds to cell surface GRP78 as its receptor and activates intracellular proliferation signaling.

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Baicalin Induces Apoptosis in Leukemia HL-60/ADR Cells via Possible Down-regulation of the PI3K/Akt Signaling Pathway

Cited by 29 publications

References 20 publications

The downregulation of c‑Myc and its target gene hTERT is associated with the antiproliferative effects of baicalin on HL‑60 cells

The downregulation of c‑Myc and its target gene hTERT is associated with the antiproliferative effects of baicalin on HL‑60 cells

Antitumor and apoptosis-promoting properties of emodin, an anthraquinone derivative from Rheum officinale Baill, against pancreatic cancer in mice via inhibition of Akt activation

GRP78 Secreted by Colon Cancer Cells Facilitates Cell Proliferation via PI3K/Akt Signaling

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