Targeting Cell Necroptosis and Apoptosis Induced by Shikonin via Receptor Interacting Protein Kinases in Estrogen Receptor Positive Breast Cancer Cell Line, MCF-7

Shahsavari, Zahra; Karami-Tehrani, Fatemeh; Salami, Siamak

doi:10.2174/1871520617666170919164055

Cited by 27 publications

(14 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As an anthraquinone compound derived from the roots of Lithospermum erythrorhizon , shikonin exhibits a broad spectrum of anti-tumor effects by inducing apoptosis in cancer of the gallbladder (18), pancreas (19), colon (20) and breast (21). The present study also demonstrated that shikonin inhibited glioma U251 cell proliferation in a dose- and time-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Shikonin inhibits proliferation and induces apoptosis in glioma cells via downregulation of CD147

et al. 2019

View full text Add to dashboard Cite

Shikonin, a traditional Chinese medicine, has been identified as being capable of inducing apoptosis in various tumors, including glioma, and is thus considered to be a promising therapeutic agent for tumor therapy. However, little is known about the molecular mechanism of shikonin in glioma. The present study investigated the influence of shikonin on the proliferation and apoptosis of glioma cells U251 and U87MG and explored the potential molecular mechanisms. It was identified that shikonin was able to induce apoptosis in human glioma cells in a time- and dose-dependent manner, and a decreased expression level of cluster of differentiation (CD)147 was observed in shikonin-treated U251 and U87MG cells. Knockdown of CD147 inhibited U251 and U87MG cell growth, whereas CD147 overexpression enhanced cell growth and decreased shikonin-induced apoptosis. Additionally, an increased expression level of CD147 suppressed the elevated production of reactive oxygen species and mitochondrial membrane potential levels induced by shikonin. The data indicated that shikonin-induced apoptosis in glioma cells was associated with the downregulation of CD147 and the upregulation of oxidative stress. CD147 may be an optional target of shikonin-induced cell apoptosis in glioma cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Shikonin inhibits proliferation and induces apoptosis in glioma cells via downregulation of CD147

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Shikonin is a naturally occurring naphthoquinone isolated from the root of the plant Lithospermum erythrorhizon, which has been widely used in the treatment of various disease [8]. In the recent years, studies have shown that shikonin and its derivatives have antitumor effects in wide range of cancer types including breast [9], lung [10], ovarian [11], liver [12], prostate [13], gastric [14] and pancreatic cancer [15]. However, the effects of shikonin in colorectal cancer cells have not been yet fully investigated yet.…”

Section: Introductionmentioning

confidence: 99%

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Qi¹,

Zhang²,

Liu³

et al. 2022

J. Cancer

View full text Add to dashboard Cite

Shikonin is a naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon, which has displayed potent anti-tumor properties. However, the effects of shikonin in colorectal cancer cells have not been yet fully investigated. In this study, we demonstrated that shikonin significantly inhibited the activity of colorectal cancer cells in a time-and dose-dependent manner. The flow cytometry and western blot results indicated that shikonin induced cell apoptosis by down-regulating BCL-2 and activating caspase-3/9 and the cleavage of PARP. The expression of BiP and the PERK/elF2α/ATF4/CHOP and IRE1α /JNK signaling pathways were upregulated after shikonin treatment. The pre-treatment with N-acetyl cysteine significantly reduced the cytotoxicity of shikonin. Taken together, shikonin could inhibit proliferation of the colorectal cancer cell through the activation of ROS mediated-ER stress. The in vivo results showed that shikonin effectively inhibited tumor growth in the HCT-116 and HCT-15 xenograft models. In conclusion, shikonin inhibited the proliferation of colorectal cancer cells in vitro and in vivo and warrants future investigation.

show abstract

“…Necroptosis is a form of regulated necrosis that depends on receptor-interacting protein kinase 1 (RIPK1) and can be specifically inhibited by necrostatin-1 (Nec-1) 6. Accumulating evidence has demonstrated that activated RIPK1 interacts with RIPK3 to facilitate RIPK1/RIPK3 necrosome formation 7,8. The necrosome recruits its downstream substrate, mixed lineage kinase domain-like protein (MLKL), which forms an oligomer, resulting in cellular membrane leakage and cell death 9.…”

Section: Introductionmentioning

confidence: 99%

<p>Shikonin-induced necroptosis in nasopharyngeal carcinoma cells via ROS overproduction and upregulation of RIPK1/RIPK3/MLKL expression</p>

Liu

Sun

Cao

2019

OTT

View full text Add to dashboard Cite

Objective: Shikonin has inhibitory effects against nasopharyngeal carcinoma that are mediated through the apoptotic pathway. However, necroptosis signaling pathways may enable the elimination of apoptosis-resistant cancers when induced with targeted therapeutic agents. Thus, there is a need to clarify whether shikonin can cause necroptosis in nasopharyngeal carcinoma and to elucidate the underlying mechanisms. Methods: In this study, we used the nasopharyngeal carcinoma cell line 5-8F and a 5-8F xenograft mouse model to evaluate the anticancer effects of shikonin. The viability and morphology of cells treated with shikonin were evaluated using CCK-8 assay and transmission electron microscopy, respectively. In addition, the expression levels of RIPK1, RIPK3, and MLKL were analyzed by western blotting, and the activities of caspase-3 and caspase-8 and levels of reactive oxygen species (ROS) were assessed. Results: Shikonin exhibited a strong inhibitory effect on 5-8F cells in vitro and in vivo. The shikonin-treated 5-8F cells presented an electron-lucent cytoplasm, loss of plasma membrane integrity, and an intact nuclear membrane, indicating that shikonin induced necroptosis. Shikonin-induced cell death was inhibited by necrostatin-1. Moreover, RIPK1, RIPK3, and MLKL were upregulated by shikonin in a dose-dependent manner. Furthermore, shikonin significantly inhibited tumor growth in the 5-8F xenograft mouse model. Conclusion: Shikonin induced 5-8F cell death via increased ROS production and the upregulation of RIPK1/RIPK3/MLKL expression, resulting in necroptosis. Thus, shikonin may represent a novel agent to treat nasopharyngeal carcinoma.

show abstract

Targeting Cell Necroptosis and Apoptosis Induced by Shikonin via Receptor Interacting Protein Kinases in Estrogen Receptor Positive Breast Cancer Cell Line, MCF-7

Abstract: On the basis of present findings, Shikonin has been suggested as a good candidate for the induction of cell death in ER+ breast cancer, although further investigations, experimental and clinical, are required.

Cited by 27 publications

References 0 publications

Shikonin inhibits proliferation and induces apoptosis in glioma cells via downregulation of CD147

Shikonin inhibits proliferation and induces apoptosis in glioma cells via downregulation of CD147

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

<p>Shikonin-induced necroptosis in nasopharyngeal carcinoma cells via ROS overproduction and upregulation of RIPK1/RIPK3/MLKL expression</p>

Contact Info

Product

Resources

About