Antitumor activity of rhein lysinate against human glioma U87 cells in vitro and in vivo

Liu, Jin; Zhang, Ke; Zhen, Yong‐Su; Wei, Jie; Hu, Gang; Gao, Junling; Tian, Ye; Lin, Yajun

doi:10.3892/or.2015.4518

Cited by 10 publications

(8 citation statements)

References 37 publications

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“…EGR1 exhibits a dual role of a tumor suppressor or a tumor-promoting factor in various carcinomas, by regulating cell cycle progression, apoptosis and malignant transformations (19)(20)(21). EGR1 stimulates cells proliferation in prostate, stomach, and kidney cancer (22)(23)(24), whereas it shows a tumor-suppressive activity in breast cancer, melanoma, fibrosarcoma and B cell lymphoma (25)(26)(27)(28). Our results also indicate a tumor-suppressive activity of EGR1 in CTCL.…”

Section: Discussionsupporting

confidence: 63%

Targeting Phosphorylation of p21-activated Kinase 1 at Thr423 Induces Cell Cycle Arrest and Apoptosis in Cutaneous T-cell Lymphoma Cells

Wang¹,

Li²,

Zhang³

et al. 2019

Acta Derm Venerol

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SIGNIFICANCEIPA-3, a small molecular inhibitor of p21-activated kinase 1 (PAK1) phosphorylation, has anti-tumor activity in multiple cancers. However, its role in cutaneous T-cell lymphoma and the underlying molecular pathogenesis are still unclear. This study investigates the role of IPA-3 on cutaneous Tcell lymphoma cells. Pho-PAK1 overexpression is seen in patients with cutaneous T-cell lymphoma. IPA-3 treatment induces apoptosis and inhibits cell growth by inducing EGR1 expression and simultaneously down-regulating the levels of BCL-2 and pho-BAD. Therefore, pho-PAK1 may be a potential tumor marker and therapeutic target of cutaneous T-cell lymphoma.Cutaneous T-cell lymphoma (CTCL) represents a rare group of extranodal T-cell lymphoproliferative diseases. Due to poor clinical outcome of CTCL, there is an urgent need for new and improved therapies. A small molecule, IPA-3, which inhibits p21-activated kinase 1 (PAK1), has shown therapeutic potential in various types of malignancies. In the present study, the anti-tumor effect of IPA-3 and its underlying molecular mechanism was evaluated. High expression of phosphorylated-PAK1 (pho-PAK1) was seen in CTCL lesional skin compared to benign inflammatory dermatoses. IPA-3 could significantly inhibit the proliferation of 3 CTCL lines in a dose-and time-dependent manner. The percentage of apoptotic cells was higher in the treatment group. Further, IPA-3 treatment caused increased EGR1 protein levels and decreased apoptosis-related BCL-2 and pho-BAD protein levels. In summary, inhibition of pho-PAK1 has significant antitumor effects in CTCL cells and it can be explored as a future therapeutic option.

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Section: Discussionsupporting

confidence: 63%

Targeting Phosphorylation of p21-activated Kinase 1 at Thr423 Induces Cell Cycle Arrest and Apoptosis in Cutaneous T-cell Lymphoma Cells

Wang¹,

Li²,

Zhang³

et al. 2019

Acta Derm Venerol

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“…For instance, RHL was shown to reduce inflammation and adipose infiltration in KK/HlJ diabetic mice with non-alcoholic fatty liver disease (10). And RHL was suggested to suppress the progression of breast and ovarian cancer, hepatocellular carcinoma, cervical cancer and lung carcinoma mainly by downregulation of Bcl-2 and cyclin D expression and upregulation of BAX and Bim expression (18). In addition, RHL was demonstrated to protect the livers by reducing the expression of TNF-α and IL-6 and the phosphorylation of SREBP-1c and ERK1/2 in diabetic mice (19).…”

Section: Discussionmentioning

confidence: 99%

Improved heart failure by Rhein lysinate is associated with p38MAPK pathway

et al. 2018

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Abstract. The present study aimed to explore the role of Rhein lysinate (RHL) in neonatal rat ventricular myocytes (NRVMs) and congestive heart failure induced by co-arctation of the abdominal aorta. Male Sprague-Dawley rats were divided into 3 groups randomly: co-arctation of abdominal aorta group (A group, n=10), sham operation group (SH group, n=10) and RHL treatment rats (A+RHL group, n=10). To establish an in vitro oxidative stressed cardiomyocyte model, NRVMs were treated with 10 µM H 2 O 2 for 24 h. MTT assay indicated that H 2 O 2 treatment reduced primary cardiomyocyte viability in a time-and dose-dependent manner, whereas RHL abolished the detrimental effects of H 2 O 2 , indicating a protective role of RHL. Further study demonstrated that H 2 O 2 -induced reactive oxygen species (ROS) production was reversed by RHL. Then, TUNEL staining was carried out and the results revealed that H 2 O 2 markedly enhanced primary cardiomyocyte apoptosis. Conversely, RHL incubation decreased H 2 O 2 -induced cell apoptosis, indicating the protective role of RHL in primary cardiomyocytes. Furthermore, abnormal p38 activation was identified in the failed heart. Notably, treatment with RHL reduced p38 activation. In addition, RHL significantly enhanced the expression of anti-apoptotic protein, B cell lymphoma (Bcl)-2, however markedly reduced the protein level of Bcl-2 associated X, apoptosis regulator in primary cardiomyocytes, indicating its anti-apoptotic role in the cardiac setting. Overall, RHL protects heart failure primarily by reducing ROS production and cardiomyocyte apoptosis via suppressing p38 mitogen activated protein kinase activation.

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“…Studies have shown that RHL is characterized by anti‐inflammatory and antitumor features . In human glioma U87 cells, RHL is shown to induce cell apoptosis via suppressing Bcl‐2 and increasing Bax expression . In cervical cancer cells, RHL is found to suppress HeLa cell growth via p38 MAPK and JNK signaling pathway .…”

Section: Introductionmentioning

confidence: 99%

“…17,18 In human glioma U87 cells, RHL is shown to induce cell apoptosis via suppressing Bcl-2 and increasing Bax expression. 19 In cervical cancer cells, RHL is found to suppress HeLa cell growth via p38 MAPK and JNK signaling pathway. 20 However, whether RHL improves SCI and the underlying mechanism has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Rhein lysinate improves motor function in rats with spinal cord injury via inhibiting p38 MAPK pathway

Hao

Wang

Daiping

et al. 2019

The Kaohsiung J of Med Scie

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The current study aims to investigate the effect of rhein lysinate (RHL) on neuromotor function in rats with spinal cord injury (SCI) and to explore the underlying mechanism. A total of 63 adult male SD rats were randomly divided into the sham group, SCI group and RHL group (SCI‐RHL group), with 21 rats in each group. Basso Beattie Bresnahan (BBB) scoring and the inclined plate test were used to evaluate the changes in motor function after SCI. Then, superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and malondialdehyde (MDA) contents were quantified. Caspase‐3‐positive cells in spinal cord tissue were detected by immunohistochemical (IHC) staining, and protein expression was detected by Western blots. Here, our data showed that compared with the SCI group, the BBB score and inclined plate test score of the SCI‐RHL group were significantly higher than those of the SCI group 7 days after the RHL intervention. After 7 days of RHL treatment, the activities of SOD and GSH‐Px in the spinal cord increased significantly. At the same time, RHL reduced the MDA content in spinal cord tissue of SCI rats. Moreover, cleaved‐caspase‐3‐positive cells and apoptotic cells were significantly lower in the SCI‐RHL group than in the SCI group. More importantly, p38 mitogen‐activated protein kinase (p38 MAPK) was significantly decreased in the SCI‐RHL group compared with the SCI group. In summary, RHL can inhibit the activation of the p38 MAPK pathway after SCI, thereby reducing the apoptosis of spinal cord neurons and improving the neuromotor function of SCI rats.

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Antitumor activity of rhein lysinate against human glioma U87 cells in vitro and in vivo

Cited by 10 publications

References 37 publications

Targeting Phosphorylation of p21-activated Kinase 1 at Thr423 Induces Cell Cycle Arrest and Apoptosis in Cutaneous T-cell Lymphoma Cells

Targeting Phosphorylation of p21-activated Kinase 1 at Thr423 Induces Cell Cycle Arrest and Apoptosis in Cutaneous T-cell Lymphoma Cells

Improved heart failure by Rhein lysinate is associated with p38MAPK pathway

Rhein lysinate improves motor function in rats with spinal cord injury via inhibiting p38 MAPK pathway

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