A 5′ AMP‐Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma

Weng, Jing Ru; Dokla, Eman M.E.; Li, Bai; Chen, Ching Shih; Chiu, Shih Jiuan; Shieh, Tzong‐Ming

doi:10.1111/bcpt.12976

Cited by 8 publications

(6 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AMPK is reported as an energy sensor and regulator of metabolism, with the suppression of immune and inflammatory processes 46. The inhibition effects of AMPK on cytokine-activated JAK/STAT had been proved in human fibrosarcoma cells and adipocytes 47, 48.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression

Chang¹,

Sia²,

Chang³

et al. 2019

Int. J. Med. Sci.

View full text Add to dashboard Cite

The proliferation and adipogenesis of preadipocytes played important roles in the development of adipose tissue and contributed much to the processes of obesity. On the other hand, lipopolysaccharide (LPS), also known as endotoxin, is a key outer membrane component of gram-negative bacteria in the gut microbiota, and has a dominant role in linking inflammation to high-fat diet-induced metabolic syndrome. Studies suggested the potential roles of LPS in hepatic steatosis and in obese mice models. However, the molecular mechanisms underlying LPS-regulated obesity remained largely unknown. Here we reported that LPS stimulated expression of cyosolic phospholipase A2 (cPLA2), one of inflammation regulators of obesity, in the preadipocytes. Pretreatment the inhibitors of JAK2, STAT3, STAT5 or AMPK significantly reduced LPS-increased mRNA and protein expression of cPLA2 together with phosphorylation of JAK2, STAT3, STAT5 and AMPK, separately. Similarly, transfection of siRNA against JAK2 or AMPK abolished expression of cPLA2 and phosphorylation of JAK2 or AMPK together with downregulated expression of JAK2 and AMPK protein. LPS enhanced activation of STAT3 and STAT5 via JAK2-dependent manner in the preadipocytes. Transfection of JAK2 or AMPK siRNA further proofed the independence of JAK2 and AMPK in LPS-treated preadipocytes. In addition, LPS-increased DNA synthesis, cell numbers and cell viability of preadipocytes were attenuated by AACOCF3, AG490, BML-275, cPLA2 siRNA, JAK2 siRNA or AMPK siRNA. Attenuation JAK2/STAT or AMPK-dependent cPLA2 expression reduced LPS-mediated adipogenesis of preadipocytes. Stimulation of arachidonic acid or AMPK activator, A-769662, increased cell numbers and cell viability and promoted differentiation of preadipocytes. Collectively, these results indicated that LPS increased preadipocytes proliferation and adipogenesis via JAK/STAT and AMPK-dependent cPLA2 expression. The mechanisms of LPS-stimulated cPLA2 expression may be a link between bacteria and obesity and provides the molecular basis for preventing metabolic syndrome or hyperplasic obesity.

show abstract

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression

Chang¹,

Sia²,

Chang³

et al. 2019

Int. J. Med. Sci.

View full text Add to dashboard Cite

show abstract

“…OSCC is a highly prevalent cancer worldwide, especially in developing regions such as Southeast China [16]. Current research has been looking into potential biomarkers and new therapeutic agents for OSCC.…”

Section: Discussionmentioning

confidence: 99%

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1

Nan

Zhong

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Emerging evidence suggests that the propagation of oral squamous cell carcinoma (OSCC) is influenced by the abnormal expression of microRNAs (miRNAs). This study aimed to characterize the involvement of miR-182-5p in OSCC by targeting the calcium/ calmodulin-dependent protein kinase II inhibitor CAMK2N1. Methods: miR-182-5p expression was quantified in OSCC tissues and cell lines with reverse transcription polymerase chain reaction (RT-PCR). Cell colony formation, Cell Counting Kit-8 (CCK-8), Ki-67, and nude mouse xenograft assays were used to characterize the role of miR-182-5p in the proliferation of OSCC. A miR-182-5p target gene was identified with western blotting, RT-PCR, and luciferase activity assays. OSCC patient survival based on CAMK2N1 expression was also analyzed. Results: miR-182-5p was up-regulated in in vitro cell lines and in vivo clinical OSCC samples. CCK-8, colony formation, and Ki-67 assays revealed that miR-182-5p promoted the growth and proliferation of OSCC cells. miR-182-5p directly targeted CAMK2N1, as evidenced by luciferase assays and target prediction algorithms. CAMK2N1 operated as a tumor suppressor gene in patients with OSCC. Down-regulating miR-182-5p expression in the CAL-27 cell line restored CAMK2N1-mediated OSCC cell proliferation. miR-182-5p expression inhibited the activation of AKT, ERK1/2, and NF-κB. Mice injected with CAL-27 cells transfected with miR-182-5p-inhibitor demonstrated a significant increase in tumor size and weight and increased CAMK2N1 mRNA and protein expression compared with the miR-negative control group. Conclusion: The miR-182-5p-CAMK2N1 pathway can be potentially targeted to regulate the proliferation of OSCC cells.

show abstract

“…After the transfected with GFP‐LC3 plasmids, cells were plated on cover slips into per well/6‐well, 30 then incubated with DMSO or JBIR‐100 or rapamycin for 30 min. Then, these cells were treated with paraformaldehyde (Merck, 2%) for 30 min at room temperature, and incubated with Triton X‐100 (0.1%) for another 20 min.…”

Section: Methodsmentioning

confidence: 99%

“…MCF‐7 cells were treated with DMSO or JBIR‐100 for 24 h, and incubated with a fixing mixture 2% paraformaldehyde for 1 h 30 . Then, cells were incubated with a buffer (1% osmic acid) for 1 h, followed by dehydration with ethanol.…”

Section: Methodsmentioning

confidence: 99%

A macrolide from Streptomyces sp. modulates apoptosis and autophagy through Mcl‐1 downregulation in human breast cancer cells

Chiu

et al. 2021

Environmental Toxicology

View full text Add to dashboard Cite

Secondary metabolites in marine organisms exhibit various pharmacological activities against diseases, such as cancer. In this study, the anti‐proliferative effect of JBIR‐100, a macrolide isolated from Streptomyces sp., was investigated in breast cancer cells. Cell growth was inhibited in response to JBIR‐100 treatment concentration‐ and time‐dependently in both MCF‐7 and MDA‐MB‐231 breast cancer cells. JBIR‐100 caused apoptosis, as verified by caspase activation and the cleavage of PARP. Western blotting revealed that JBIR‐100 modulated the expression of Akt/NF‐κB signaling components and Bcl‐2 family members. Overexpression of Mcl‐1 partially rescued MCF‐7 cells from JBIR‐100‐induced cytotoxicity. In addition, transmission electron microscopy analyses, confocal analysis, and western blot assay indicated that JBIR‐100 inhibited autophagy in MCF‐7 cells. Exposure to the autophagy inhibitor did not synergize JBIR‐100‐induced apoptosis. In summary, our results suggested that JBIR‐100 may be potentially used for breast cancer therapy.

show abstract

A 5′ AMP‐Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma

Cited by 8 publications

References 35 publications

Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression

Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1

A macrolide from Streptomyces sp. modulates apoptosis and autophagy through Mcl‐1 downregulation in human breast cancer cells

Contact Info

Product

Resources

About