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Long non-coding RNAs (lncRNAs) are well known for their oncogenic or anti-oncogenic roles in cancer development. AGAP2-AS1, a new lncRNA, has been extensively demonstrated as an oncogenic lncRNA in various cancers. Abundant experimental results have proved the aberrantly high level of AGAP2-AS1 in a great number of malignancies, such as glioma, colorectal, lung, ovarian, prostate, breast, cholangiocarcinoma, bladder, colon and pancreatic cancers. Importantly, the biological functions of AGAP2-AS1 have been extensively demonstrated. It could promote the proliferation, migration and invasion of cancer cells. Simultaneously, the clinical significances of AGAP2-AS1 were also illustrated. AGAP2-AS1 was exceptionally overexpressed in various cancer tissues. Clinical studies disclosed that the abnormal overexpression of AGAP2-AS1 was tightly connected with overall survival (OS), lymph nodes metastasis (LNM), clinical stage, tumor infiltration, high histological grade (HG), serous subtype and PFI times. However, to date, the biological actions and clinical significances of AGAP2-AS1 have not been systematically reviewed in human cancers. In the present review, the authors overviewed the biological actions, potential mechanisms and clinical features of AGAP2-AS1 according to the previous studies. In summary, AGAP2-AS1, as a vital oncogenic gene, is a promising biomarker and potential target for carcinoma prognosis and therapy.

Natural products are a precious source of promising leads for the development of novel cancer therapeutics. Recently, triterpenoids in Alismatis rhizoma has been widely demonstrated for their anti-cancer activities in cancer cells. In this study, we examined the inhibitory effects of alisol A in human breast cancer cells. We demonstrated that alisol A exhibited significant anti-proliferative effects in MDA-MB-231 cells and this response was related to autophagy induction. Alisol A-induced autophagy was supported by the triggered autophagosome formation and increased LC3-II levels. Interestingly, autophagy inhibitor 3-MA significantly reversed the cytotoxic effects induced by alisol A. Meanwhile, alisol A-induced autophagy was significantly inhibited by 3-MA in MDA-MB-231 cells. Cell cycle analysis revealed that alisol A arrested the cell cycle at G0/G1 phase. The expression level of cell cycle regulatory proteins cyclin D1 was significantly down regulated. In addition, the suppression of NF-κB and PI3K/Akt/mTOR pathways in MDA-MB-231 cells was observed. Furthermore, alisol A significantly suppressed the migration and invasion of MDA-MB-231 cells by inhibiting the expression levels of MMP-2 and MMP-9. Taken together, our results demonstrated that alisol A could inhibit the proliferation and metastasis of MDA-MB-231 cells. It could be a promising agent for breast cancer therapy.

Eupatorium lindleyanum DC. (EL) has a long history of traditional use in China to cure coughs, chronic bronchitis, lobar pneumonia, and hypertension. Because of this extensive use of EL in traditional medicine, this present review gives a systematic overview of the conventional applications, phytochemistry, and pharmacological effects of the herb. Literature was systematically searched using the scientific databases ScienceDirect, SciFinder, CNKI, Wiley, Baidu Scholar, SpringerLink, PubMed, Web of Science, and other professional websites. Information was also gathered from books on traditional Chinese herbal medicine, the Chinese Pharmacopoeia and Chinese Materia Medica. To date, many preparations of EL have been widely used clinically to treat various diseases of the respiratory system. More than 100 compounds have been isolated from the herb, including triterpenes, sesquiterpenes, sesquiterpene lactones, flavonoids, acyclic diterpenoids, sterols, and so on. Among them, terpenoids are considered to be the most important bioactive substances in EL. The pharmacological functions of EL, including anti-asthmatic, anti-tussive, anti-inflammatory, anti-hyperlipidemic, anti-hypertensive, anti-virus, and anti-tumor activities, have been widely investigated. However, most of the studies are preclinical research. Further studies are required to examine the underlying mechanisms of action. Traditionally, EL is used for treating many diseases, especially respiratory diseases. Unfortunately, up to now, modern studies have not yet well elucidated the conventional usage of EL. Most importantly, its biological activities and the corresponding constituents are still unclear. Moreover, studies on the pharmacokinetics and toxicity of EL are few, so data on the clinical safety of EL are lacking. Taken together, research work on EL is quite preliminary. More in-depth studies of phytochemistry, pharmacological activities, pharmacokinetics, and toxicity of the herb are needed. This review aims to provide valuable information on EL to guide future investigations and applications.

Persistent activation of STAT3 plays an important role in the development of triple-negative breast cancer (TNBC), and suppression of STAT3 is considered as a novel approach for cancer therapy. In this project, we aimed to examine the anticancer activity and molecular mechanism of eupalinolide J (EJ) in TNBC cells. The presented results demonstrated that the growth of human TNBC cells (MDA-MB-231 and MDA-MB-468 cells) was obviously inhibited by EJ. The IC values were 3.74 ± 0.58 and 4.30 ± 0.39 μM, respectively. Further study demonstrated that EJ suppressed the proliferation of TNBC cells mainly through cell apoptosis induction, mitochondrial membrane potential (MMP) disruption, and cell cycle arrest. Meanwhile, the STAT3 and p-STAT3 in EJ-treated TNBC cells were remarkably suppressed. Importantly, silencing of STAT3 by STAT3-shRNA significantly blunted the anticancer activities of EJ in TNBC cells, suggesting that EJ suppressed cancer cell proliferation targeting the STAT3 pathway. Notably, further study demonstrated that EJ significantly promoted the degradation of STAT3 in TNBC cells. Finally, EJ exhibited an effective antitumor activity against MDA-MB-231 cells . In conclusion, we identified that EJ suppressed the growth of TNBC cells targeting the STAT3 signaling pathway. These results strongly support that EJ is a promising therapeutic agent for TNBC.

The present authors have recently demonstrated that hirsutine, one of the major alkaloids in Uncaria species, promotes cell apoptosis by inducing DNA damage and suppresses metastasis of breast cancer cells. Despite its potent anti-cancer activity, certain types of human breast cancer cells exhibit resistance to hirsutine. To maximize the clinical utility of hirsutine therapy against breast cancer, it is critical to explore the underlying mechanism that protects hirsutine-resistant breast cancer cell lines. To identify potential targets for overcoming hirsutine-resistance, the present study investigated a library of kinase inhibitors in combination with hirsutine treatment in the hirsutine-resistant human breast carcinoma MCF-7 cell line. Amongst the 96 compounds tested, inhibitors of the ataxia telangiectasia mutated (ATM) pathway sensitized MCF-7 cells to hirsutine-induced cell death along with a sustained DNA damage response. This sensitization of MCF-7 cells to the hirsutine-induced DNA damage response by interfering with the ATM pathway did not require p53. Instead, radical oxygen species generation was significantly increased in hirsute and ATM inhibitor-treated MCF-7 cells. In conclusion, the present findings suggest the importance of the ATM pathway for optimizing the anti-cancer effect of hirsutine in breast cancer cells.

Arctigenin is a bioactive lignan isolated from the seeds of Arctium lappa L. which has been widely used as a diuretic and a diaphoretic in Traditional Chinese Medicine. In the present study, the authors investigated the effects of arctigenin on tumor migration and invasion in aggressive human breast cancer cells. The MTT assay results showed that arctigenin did not show a significant cytotoxic effect on the cell viability of MDA-MB-231 cells. However, wound healing migration and Boyden chamber invasion assays demonstrated that arctigenin significantly inhibited in vitro migration and invasion of the MDA-MB-231 cells. Furthermore, gelatin zymography results showed that arctigenin reduced the activity of MMP-2 and MMP-9. Western blot analysis results demonstrated that the expression of MMP-2, MMP-9 and heparanase proteins was significantly downregulated following the treatment of arctigenin. Finally, the antiangiogenic activity of arctigenin was also examined by the chick embryo chorioallantoic membrane (CAM) assay. Arctigenin treatment significantly inhibited angiogenesis in the CAM. In conclusion, the results revealed that arctigenin significantly inhibited the migration and invasion of MDA-MB-231 cells by downregulating MMP-2, MMP-9 and heparanase expression. However, further studies are still necessary to investigate the exact mechanisms involved and to explore signal transduction pathways to better understand the biological mechanisms.

Nuclear factor-κB (NF-κB) activation has been implicated not only in carcinogenesis but also in cancer cell invasion and metastatic process; therefore, targeting the NF-κB pathway is an attractive strategy for controlling metastasis. Amongst 56 chemically defined compounds derived from natural products, we have identified a new phytochemical compound Hirsutine, which strongly suppresses NF-κB activity in murine 4T1 breast cancer cells. In accordance with the NF-κB inhibition, Hirsutine reduced the metastatic potential of 4T1 cells, as seen in the inhibition of the migration and invasion capacity of 4T1 cells. Hirsutine further inhibited the constitutive expression of MMP-2 and MMP-9 in 4T1 cells, and reduced the in vivo lung metastatic potential of 4T1 cells in the experimental model. Given that the migration of human breast cancer cells was also inhibited, our present study implies that Hirsutine is an attractive phytochemical compound for reducing metastasis potential of cancer cells by regulating tumor-promoting NF-κB activity.

Sesquiterpene lactones have been confirmed to have potential antitumor activity. Here, we demonstrated that Eupalinolide O (EO), a novel sesquiterpene lactone isolated from Eupatorium lindleyanum DC., showed significant anticancer activity against human MDA-MB-468 breast cancer cells. The cytotoxicity induced by EO was mediated by induction of apoptosis. Flow cytometric analysis demonstrated that EO treatment resulted in loss of the mitochondrial membrane potential in cancer cells which is regarded as a hallmark of apoptosis. Further study demonstrated that EO induced apoptotic cell death in the MDA-MB-468 cells through the activation of caspases. The effect of EO on the induction of apoptosis was significantly prevented by the treatment of pan-caspase inhibitor Z-VAD-FMK. We also found that EO treatment resulted in cell cycle arrest in the G2/M phase. The expression of cell cycle-related proteins (cyclin B1 and cdc2) was significantly decreased. Furthermore, the suppression of the Akt pathway in the MDA-MB-468 cells was observed. Collectively, EO suppressed the growth of the MDA-MB-468 cells possibly by cell cycle arrest in the G2/M phase and the induction of caspase-dependent apoptosis. These results suggest that EO is a promising natural compound for breast cancer therapy.

Hirsutine is one of the major alkaloids isolated from plants of the Uncaria genus and is known for its cardioprotective, anti-hypertensive and anti-arrhythmic activities. We recently reported that hirsutine is an anti-metastatic phytochemical by targeting NF-κB activation in a murine breast cancer model. In the present study, we further examined the clinical utility of hirsutine against human breast cancer. Among six distinct human breast cancer cell lines, hirsutine showed strong cytotoxicity against HER2-positive/ p53-mutated MDA-MB-453 and BT474 cell lines. Conversely, HER2-negative/p53 wild-type MCF-7 and ZR-75-1 cell lines showed resistance against hirsutine-induced cytotoxicity. Hirsutine induced apoptotic cell death in the MDA-MB-453 cells, but not in the MCF-7 cells, through activation of caspases. Furthermore, hirsutine induced the DNA damage response in the MDA-MB-453 cells, but not in the MCF-7 cells, as highlighted by the upregulation of γH2AX expression. Along with the induction of the DNA damage response, the suppression of HER2, NF-κB and Akt pathways and the activation of the p38 MAPK pathway in the MDA-MB-453 cells were observed. Considering that there was no difference between MDA-MB-453 and MCF-7 cells in regards to irinotecan-induced DNA damage response, our present results indicate the selective anticancer activity of hirsutine in HER2-positive breast cancer by inducing a DNA damage response.

High power continuous wave (CW) CO2 laser cladding was performed on H13 steel, pre-coated by superfine WC. After laser cladding, the materials were tempered for 6 hours. Scanning electronic microscopy (SEM) was used to observe the morphologies of the cladding layer. X-ray diffraction (XRD) was employed to analyze the microstructure of the cladding layer. The changes of microhardness, temper resistance and wear resistance were tested. The microhardness of cladding layer before tempering was 1.4 times of that of base metal and 1.9 times after tempering at 500°C. The wear resistance and tempering resistance were improved.