Rhein Inhibits the Migration of Ovarian Cancer Cells through Down-Regulation of Matrix Metalloproteinases

Ren, Baoyin; Guo, Weijia; Tang, Yawei; Zhang, Jing; Xiao, Nan; Zhang, Lin; Li, Weiling

doi:10.1248/bpb.b18-00431

Cited by 23 publications

(17 citation statements)

References 23 publications

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“…Rhein was shown to reduce the activity of Rac1 and AP-1, thereby regulating its downstream ROS-dependent signaling axis p38/JNK MAPK in SKOV3-PM4 cells, and attenuating cellular proliferation, migration, and invasion [53]. Rhein also inhibited matrix metalloproteinases in A2780 and OV2008 cell lines [159].…”

Section: Ovarian Cancermentioning

confidence: 98%

Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties

et al. 2020

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According to the World Health Organization (WHO), cancer is the second-highest cause of mortality in the world, and it kills nearly 9.6 million people annually. Besides the fatality of the disease, poor prognosis, cost of conventional therapies, and associated side-effects add more burden to patients, post-diagnosis. Therefore, the search for alternatives for the treatment of cancer that are safe, multi-targeted, effective, and cost-effective has compelled us to go back to ancient systems of medicine. Natural herbs and plant formulations are laden with a variety of phytochemicals. One such compound is rhein, which is an anthraquinone derived from the roots of Rheum spp. and Polygonum multiflorum. In ethnomedicine, these plants are used for the treatment of inflammation, osteoarthritis, diabetes, and bacterial and helminthic infections. Increasing evidence suggests that this compound can suppress breast cancer, cervical cancer, colon cancer, lung cancer, ovarian cancer, etc. in both in vitro and in vivo settings. Recent studies have reported that this compound modulates different signaling cascades in cancer cells and can prevent angiogenesis and progression of different types of cancers. The present review highlights the cancer-preventing and therapeutic properties of rhein based on the available literature, which will help to extend further research to establish the chemoprotective and therapeutic roles of rhein compared to other conventional drugs. Future pharmacokinetic and toxicological studies could support this compound as an effective anticancer agent.

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Section: Ovarian Cancermentioning

confidence: 98%

Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties

et al. 2020

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“…Rhein is one of the effective components extracted from Polygonaceae plants [8]. A large number of literatures have reported that rhein plays an antitumor role by inducing tumor cell apoptosis, affecting tumor cell proliferation, and inhibiting tumor cell migration and invasion in breast cancer, colon cancer, and lung cancer cells [9][10][11][12][13][14][15][16]. However, the mechanism of its action on proliferation and metastasis and the signaling pathways involved are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Rhein Inhibits the Progression of Chemoresistant Lung Cancer Cell Lines via the Stat3/Snail/MMP2/MMP9 Pathway

Liu

Ding

Liu

et al. 2022

BioMed Research International

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Chemotherapy is a common drug for lung cancer. Nevertheless, the development of drug resistance greatly limits their clinical efficacy. Therefore, to reduce drug resistance, we need to constantly explore new treatments. This study is aimed at determining the role of rhein in the proliferation and metastasis of lung cancer cell. Our study found that rhein significantly inhibits the proliferation and migration of lung cancer cells. Additionally, the mRNA expression and protein levels of Snail, MMP2, and MMP9 are decreasing in lung cancer cells treated by rhein. Our results showed that rhein plays a vital role in proliferation and metastasis of chemosensitive and chemoresistant lung cancer cells, and the mechanism may be related to the Stat3/Snail/MMP2/MMP9 pathway.

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“…Previous studies have suggested that rhein inhibits non-small cell lung cancer cell growth in vitro and in vivo by suppressing the STAT3 signaling pathway [ 19 ] and inducing HepaRG cell death through S-phase cell cycle arrest and apoptosis [ 20 ]. In addition, anticancer activity of rhein has been observed in breast [ 21 ], ovarian [ 22 ], and colon [ 23 ] cancers, suggesting that it may be a novel agent for the prevention and treatment of CRC.…”

Section: Introductionmentioning

confidence: 99%

Rhein Suppresses Colorectal Cancer Cell Growth by Inhibiting the mTOR Pathway In Vitro and In Vivo

Zhang

Yi²,

Huang

et al. 2021

Cancers

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Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. Rhein has demonstrated therapeutic effects in various cancer models. However, its effects and underlying mechanisms of action in CRC remain poorly understood. We investigated the potential anticancer activity and underlying mechanisms of rhein in CRC in vitro and in vivo. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of rhein on CRC cells. Wound-healing and Transwell assays were conducted to assess cell migration and invasion capacity. Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. A tissue microarray was used to detect mTOR expression in CRC patient tissues. Gene overexpression and knockdown were done to analyze the function of mTOR in CRC. The anticancer effect of rhein in vivo was assessed in a CRC xenograft mouse model. The results show that rhein significantly inhibited CRC cell growth by inducing S-phase cell cycle arrest and apoptosis. Rhein inhibited CRC cell migration and invasion through the epithelial–mesenchymal transition (EMT) process. mTOR was highly expressed in CRC cancer tissues and cells. Overexpression of mTOR promoted cell growth, migration, and invasion, whereas mTOR knockdown diminished these phenomena in CRC cells in vitro. In addition, rhein directly targeted mTOR and inhibited the mTOR signaling pathway in CRC cells. Rhein promoted mTOR degradation through the ubiquitin-proteasome pathway. Intraperitoneal administration of rhein inhibited HCT116 xenograft tumor growth through the mTOR pathway. In conclusion, rhein exerts anticancer activity in vitro and in vivo by targeting mTOR and inhibiting the mTOR signaling pathway in CRC. Our results indicate that rhein is a potent anticancer agent that may be useful for the prevention and treatment of CRC.

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Rhein Inhibits the Migration of Ovarian Cancer Cells through Down-Regulation of Matrix Metalloproteinases

Cited by 23 publications

References 23 publications

Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties

Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties

Rhein Inhibits the Progression of Chemoresistant Lung Cancer Cell Lines via the Stat3/Snail/MMP2/MMP9 Pathway

Rhein Suppresses Colorectal Cancer Cell Growth by Inhibiting the mTOR Pathway In Vitro and In Vivo

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