Shikonin time-dependently induced necrosis or apoptosis in gastric cancer cells via generation of reactive oxygen species

Lee, Mu-Jang; Kao, Shao‐Hsuan; Hunag, Jing-En; Sheu, Gwo‐Tarng; Yeh, Chi-Wei; Hseu, You‐Cheng; Wang, Chau‐Jong; Hsu, Li‐Sung

doi:10.1016/j.cbi.2014.01.008

Cited by 49 publications

(48 citation statements)

References 32 publications

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“…Shikonin is also reported to influence apoptosis to some extent (Chang et al 2010;Liu et al 2014) and can regulate the AKT/ASK1/p38 pathway or reactive oxygen species levels to induce apoptosis (Ahn et al 2013;Duan et al 2014;Lee et al 2014). Our study revealed that a low concentration of shikonin has no apparent effect on apoptosis, but in the presence of TNF-␣, shikonin induces apoptosis in a concentrationdependent manner, promotes the activation of caspase-3 and (G, H) The expression levels of cyclin D1 and cyclin E were measured by Western blot after treatment with different concentrations of shikonin and TNF-␣.…”

Section: Discussionmentioning

confidence: 95%

Shikonin inhibits TNF-α-induced growth and invasion of rat aortic vascular smooth muscle cells

Zhang

et al. 2015

Can. J. Physiol. Pharmacol.

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Shikonin is a naphthoquinone compound extracted from the Chinese herb purple gromwell. Shikonin has broad antibacterial, anti-inflammatory, and antitumor activities. The tumor necrosis factor-α (TNF-α)-induced proliferation and invasion of vascular smooth muscle cells (VSMCs) is an important factor that contributes to atherosclerosis. The effects of shikonin on the proliferation and apoptosis of VSMCs have been reported; however, the function of shikonin on TNF-α-mediated growth and invasion of VSMCs during atherosclerosis remains unclear. In this study, we used Western blot, flow cytometry, real-time quantitative PCR, and enzyme-linked immunosorbent assay to investigate the effect of shikonin on the TNF-α-induced growth and invasion of VSMCs and to determine the underlying mechanism. Our results showed that shikonin inhibits the TNF-α-mediated growth and invasion. Further study revealed that shikonin regulates the activation of nuclear factor kappa B and phosphatidyl inositol 3-kinase signaling pathways; modulates the expression of cyclin D1, cyclin E, B-cell lymphoma 2, and Bax; activates caspase-3 and caspase-9; induces cell cycle arrest; and promotes the apoptosis of VSMCs. Together, our results indicate that shikonin may become a promising agent for the treatment of atherosclerosis and they also establish foundation for the development of anti-atherosclerosis drugs.

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Section: Discussionmentioning

confidence: 95%

Shikonin inhibits TNF-α-induced growth and invasion of rat aortic vascular smooth muscle cells

Zhang

et al. 2015

Can. J. Physiol. Pharmacol.

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“…For instance, shikonin induction of apoptosis in Bcr/Abl chronic myelogenous leukemia cells works through ROS-mediated JNK activation [44]. In the human gastric cancer cell line AGS, shikonin induces apoptosis through the inhibition of PI3K/Akt and ERK activities and the augmentation of p38 activity [45]. In the cervical cancer cell line HeLa, the colon cancer cell line Hct116, the lung cancer cell line A549, and the hepatocellular carcinoma cell lines Hep3B, BEL7402, and Huh7, shikonin increases ROS production, inactivates PI3K/Akt, and subsequently promotes apoptosis [46,47].…”

Section: Discussionmentioning

confidence: 99%

Shikonin inhibits oxidized LDL-induced monocyte adhesion by suppressing NFκB activation via up-regulation of PI3K/Akt/Nrf2-dependent antioxidation in EA.hy926 endothelial cells

Huang

Lin

Yang

et al. 2015

Biochemical Pharmacology

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“…Cells were washed another three times by PBS and then observed under a fluorescene microscope. ROS was also measured as previously described [19]. The cells were lysed using 1% SDS and sonicated.…”

Section: Methodsmentioning

confidence: 99%

Estrogen-Related Receptor Alpha Confers Methotrexate Resistance via Attenuation of Reactive Oxygen Species Production and P53 Mediated Apoptosis in Osteosarcoma Cells

Chen

Wang

Duan

et al. 2014

BioMed Research International

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Osteosarcoma (OS) is a malignant tumor mainly occurring in children and adolescents. Methotrexate (MTX), a chemotherapy agent, is widely used in treating OS. However, treatment failures are common due to acquired chemoresistance, for which the underlying molecular mechanisms are still unclear. In this study, we report that overexpression of estrogen-related receptor alpha (ERRα), an orphan nuclear receptor, promoted cell survival and blocked MTX-induced cell death in U2OS cells. We showed that MTX induced ROS production in MTX-sensitive U2OS cells while ERRα effectively blocked the ROS production and ROS associated cell apoptosis. Our further studies demonstrated that ERRα suppressed ROS induction of tumor suppressor P53 and its target genes NOXA and XAF1 which are mediators of P53-dependent apoptosis. In conclusion, this study demonstrated that ERRα plays an important role in the development of MTX resistance through blocking MTX-induced ROS production and attenuating the activation of p53 mediated apoptosis signaling pathway, and points to ERRα as a novel target for improving osteosarcoma therapy.

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Shikonin time-dependently induced necrosis or apoptosis in gastric cancer cells via generation of reactive oxygen species

Cited by 49 publications

References 32 publications

Shikonin inhibits TNF-α-induced growth and invasion of rat aortic vascular smooth muscle cells

Shikonin inhibits TNF-α-induced growth and invasion of rat aortic vascular smooth muscle cells

Shikonin inhibits oxidized LDL-induced monocyte adhesion by suppressing NFκB activation via up-regulation of PI3K/Akt/Nrf2-dependent antioxidation in EA.hy926 endothelial cells

Estrogen-Related Receptor Alpha Confers Methotrexate Resistance via Attenuation of Reactive Oxygen Species Production and P53 Mediated Apoptosis in Osteosarcoma Cells

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