Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling

Chen, Shurui; Liu, Wei; Wang, Ke; Fan, Yanli; Chen, Jiaqi; Ma, Jianbin; Wang, Xinyang; He, Dalin; Zeng, Jin; Li, Lei

doi:10.1371/journal.pone.0173725

Cited by 30 publications

(24 citation statements)

References 30 publications

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“…[40][41][42] In this study, RNA interference experiment was carried out to clarify whether MMP-2 and MMP-9 was associated with the cell metastasis in Hep3B cells. We have observed that knockdown of MMP-2 and MMP-9 could inhibit the cell migration and invasion ability in Hep3B cells.…”

Section: Discussionmentioning

confidence: 99%

Chelerythrine Inhibits Human Hepatocellular Carcinoma Metastasis <i>in Vitro</i>

Zhu

Pan

Zhang

et al. 2018

Biological & Pharmaceutical Bulletin

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Chelerythrine (CHE) is a type of benzophenanthridine alkaloid found in many herbs and is also the main alkaloid constituent of Toddalia asiatica (L.) LAM. It has been proven to have various activities including antitumor, antifungal, anti-inflammatory and anti-parasitic effects. We have previously demonstrated that CHE can inhibit proliferation and promote apoptosis in human hepatocellular carcinoma (HCC) cells. However, the effect of CHE on the metastasis of HCC and its related molecular mechanisms have yet to be validated. In this study, we investigated the effects of CHE on the migration and invasion of the HCC cell line Hep3B. Key words Chelerythrine; hepatocellular carcinoma; metastasis Despite the groundbreaking progress in the diagnosis and treatment of malignant tumors, cancer remains the greatest health concern in the world due to high morbidity and mortality.1) Hepatocellular carcinoma (HCC) is one of the most common types of cancer and the second leading cause of cancer-related death with the 5th highest morbidity rate according to recent studies.2,3) Currently, there are a few treatment options of HCC, including surgical resection and liver transplantation. However, most of the patients who undergo the treatments mentioned above experience new tumors in the residual liver, and their five-year survival rate is no more than 10%.4-6) Metastasis and recurrence are the two main reasons for poor prognosis in patients with HCC. 7) Therefore, key efforts should be focused on blocking invasion and migration of cancer cells.Natural products have been used to treat cancer for over 40 years. Approximately 60% of the clinically used anti-cancer drugs are natural products or derivatives.8) The traditional Chinese medicinal herb Toddalia asiatica LAM. is a kind of traditional folk medicine commonly used in southwest China. It can disperse pathogenic wind and relieve pain, remove blood stasis to stop bleeding, clear away toxic materials and alleviate edema, as stated in the Chinese theory of medicine. We extracted total alkaloids from Toddalia asiatica LAM. and observed obvious anti-inflammatory, analgesic and anti-tumor effects. 10,11) CHE has a wide range of biological activities including antimicrobial, antifungal, anti-inflammatory, anti-parasitic and anti-tumor effects. [11][12][13][14] Regarding cancer therapy, we have reported that CHE can inhibit proliferation and promote apoptosis in HepG2 cells.15) However, the effect of CHE on the metastasis of HCC and its related molecular mechanisms are still undefined.Studies have shown that tumor metastasis involves a serious of complex processes. The primary tumor cells proliferate, invade the basement membrane (BM) and enter the blood and lymphatic circulation. Finally, metastases are formed at distal sites, resulting in secondary tumors. 16,17) In the process described above, the degradation of the extracellular matrix (ECM) is key to tumor migration and invasion. Many protein kinases play important roles in the degradation of the ECM, including matrix metalloprote...

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Section: Discussionmentioning

confidence: 99%

Chelerythrine Inhibits Human Hepatocellular Carcinoma Metastasis <i>in Vitro</i>

Zhu

Pan

Zhang

et al. 2018

Biological & Pharmaceutical Bulletin

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“…NF‐κB is a complex family, thus, further investigations are needed in the future. The epithelial‐mesenchymal transition (EMT) had been shown to get cells to obtain strong capability of motility for leading cells to metastasis to the distant regions . During EMT, epithelial phenotype transforms into mesenchymal phenotype .…”

Section: Discussionmentioning

confidence: 99%

“…TET inhibits Wnt/β‐catenin pathway and decreases metastatic tumor antigen 1 (MTA1) expression to modulate hepatocellular carcinoma cell metastasis . TET inhibited migration and invasion of renal cell carcinoma partially by regulating Akt/NF‐κB/MMP‐9 signaling pathway and suppresses metastatic phenotype of prostate cancer cells by regulating Akt/mTOR/MMP‐9 signaling pathway . However, there is no available information to show TET affect cell migration and invasion on human brain Glioblastoma multiforme 8401 cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Tetrandrine inhibits human brain glioblastoma multiforme GBM 8401 cancer cell migration and invasion in vitro

Jiang

Cheng

Kuo

et al. 2018

Environmental Toxicology

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Tetrandrine (TET) has been reported to induce anti-cancer activity in many human cancer cells and also to inhibit cancer cell migration and invasion. However, there are no reports to show TET inhibits cell migration and invasion in human brain glioblastoma multiforme GBM 8401 cells. In this study, we investigated the anti-metastasis effects of TET on GBM 8401 cells in vitro. Under sub-lethal concentrations (from 1, 5 up to 10 μM), TET significantly inhibited cell mobility, migration and invasion of GBM 8401 cells that were assayed by wound healing and Transwell assays. Gelatin zymography assay showed that TET inhibited MMP-2 activity in GBM 8401 cells. Western blotting results indicated that TET inhibited several key metastasis-related proteins, such as p-EGFR (Tyr1068) , SOS-1, GRB2, Ras, p-AKT (Ser473) and p-AKT (Thr308) , NF-κB-p65, Snail, E-cadherin, N-cadherin, NF-κB, MMP-2 and MMP-9 that were significant reduction at 24 and 48 hours treatment by TET. TET reduced MAPK signaling associated proteins such as p-JNK1/2 and p-c-Jun in GBM 8401 cells. The electrophoretic mobility shift (EMSA) assay was used to investigate NF-κB and DNA binding was reduced by TET in a dose-dependently. Based on these findings, we suggested that TET could be used in anti-metastasis of human brain glioblastoma multiforme GBM 8401 cells in the future. K E Y W O R D S GBM 8401 cells, migration and invasion, MMP-2, NF-κB, Tetrandrine (TET) 1 | INTRODUCTION Malignant glioblastoma multiforme (GBM) are the most common and aggressive malignant primary brain tumor in humans and can be a fatal tumor because of difficulties in treating the related metastasis due to the high proliferation rate and invasiveness. 1-5 Currently, the treatment of GBM is the local irradiation, and conventional chemotherapy with temozolomide (TMZ) or surgical resection in combination with radiotherapy and chemotherapy but the median survival rate is only 8-15 months. 4-6 About 20% of patients after treated with TMZ have shown the clinical toxicity. 7 Due to the side effects of TMZ chemotherapy that leading to the limited efficiency. Thus, bases on the Yun-Lian Lin and Jing-Gung Chung contributed equally to this study.

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“…Tetrandrine has broad-spectrum antitumor effects (Bhagya and Chandrashekar 2018;Liu 2017;Liu et al 2016) in many types of cancer cells, including human liver cancer (Zhang et al 2018a;Yu and Ho 2013), osteosarcoma Lu et al 2017), oral cancer (Lien et al 2017;Huang et al 2013), colon carcinoma (Meng et al 2004;Li et al 2019), gastric cancer (Bai et al 2018;Qin et al 2013), brain glioblastoma multiforme GBM 8401 cancer (Jiang et al 2019) and lung carcinoma (Chow et al 2018;Cho et al 2009). It also exhibits antineoplastic activity against gallbladder carcinoma (Zhu et al 2014), thyroid carcinoma B-CPAP cells ), prostatic carcinoma PC3 cells (Lan et al 2018), esophageal cancer , breast cancer (Guo and Pei 2019), pancreatic cancer (Singh et al 2018), nasopharyngeal carcinoma (Lin et al 2016(Lin et al , 2017b, acute megakaryoblastic leukemia (Liu et al 2017c), cervical cancer (Zhang et al 2018b) and renal carcinoma (Chen et al 2014(Chen et al , 2017a cells. Although tetrandrine exhibited broad anti-tumor effects, a number of these studies lacked positive controls or anti-tumor evaluation of tetrandrine in vivo.…”

Section: Anti-inflammatory Effectsmentioning

confidence: 99%

“…Reversal of multidrug resistance is an additional important mechanism of the anticancer effects of tetrandine (9) and fangchinoline (10). These two compounds are effective in overcoming multidrug resistance in a variety of tumor cells in a synergistic manner via modulation of P-glycoprotein (Choi et al 1998;Sun and Wink 2014;Lu et al 2017), multidrug resistance-associated protein 1 , multidrug efflux transporters (Yao et al 2017), Akt/NF-jB/matrix metalloprotein (MMP)-9 (Chen et al 2017a) and b-catenin expression (Zhang et al 2017b). Tetrandine has also been shown to enhance radiation sensitization for human nasopharyngeal carcinoma cells by modulating phosphorylated histone H2AX (c-H2AX), phosphorylated CDC25C, phosphorylated cyclin-dependent kinase 1 (p-CDK1) and CDK1 (Ding et al 2008;Wang et al 2017c).…”

Section: Anti-inflammatory Effectsmentioning

confidence: 99%

A critical review: traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji)

2020

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Stephania tetrandra S. Moore (S. tetrandra) is distributed widely in tropical and subtropical regions of Asia and Africa. The root of this plant is known in Chinese as ''Fen Fang Ji''. It is commonly used in traditional Chinese medicine to treat arthralgia caused by rheumatism, wet beriberi, dysuria, eczema and inflamed sores. Although promising reports have been published on the various chemical constituents and activities of S. tetrandra, no review comprehensively summarizes its traditional uses, phytochemistry, pharmacology and toxicology. Therefore, the review aims to provide a critical and comprehensive evaluation of the traditional use, phytochemistry, pharmacological properties, pharmacokinetics and toxicology of S. tetrandra in China, and meaningful guidelines for future investigations.

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Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling

Cited by 30 publications

References 30 publications

Chelerythrine Inhibits Human Hepatocellular Carcinoma Metastasis <i>in Vitro</i>

Chelerythrine Inhibits Human Hepatocellular Carcinoma Metastasis <i>in Vitro</i>

Tetrandrine inhibits human brain glioblastoma multiforme GBM 8401 cancer cell migration and invasion in vitro

A critical review: traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji)

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