Sanmiao wan alleviates inflammation and exhibits hypouricemic effect in an acute gouty arthritis rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanmiao wan (SMW), a classical traditional Chinese medicine (TCM) formula, has been employed to treat gouty diseases in clinic as early as Yuan dynasty. It shows remarkably therapeutic effects in acute gouty arthritis (GA). However, the potential mechanisms of SMW are still not fully revealed. AIM OF THE STUDY: The objective of this project is to evaluate the pharmacological effects and possible mechanisms of SMW in a rat model of acute GA. MATERIALS AND METHODS: Monosodium urate (MSU) suspension was injected into the ankle joint of rats to establish acute GA model. The inflammation was evaluated by measuring the posterior ankle diameter. The pathological status of synovial tissue was assessed by hematoxylin eosin (HE), Masson, and picrosirius red staining. The level of IL-6 was measured using ELISA kit. The levels of blood urea nitrogen (BUN), creatinine (CR), UA (uric acid), and xanthine oxidase (XOD) in the serum were measured using standard diagnostic kits. The percentage of Th17 cells in blood samples was performed using flow cytometry. Moreover, RT-qPCR was performed to examine the mRNA level of RANK, RORγt, RANKL, and STAT3 in the synovial tissue. Furthermore, immunofluorescence was carried out to assess the expression of STAT3 in the synovial tissue. RESULTS: SMW effectively alleviated the inflammation and improved the pathological status of the ankle joint in rats with acute GA. It significantly suppressed the release of proinflammatory cytokine (IL-6). Meanwhile, the levels of UA, BUN, and CR were markedly reduced after SMW treatment. A remarkable reduction of XOD activity was observed in the study. Importantly, SMW treatment significantly reduced the frequency of Th17 cells, decreased the mRNA levels of RANK, RORγt, RANKL, and STAT3 in the synovial tissue. Furthermore, the suppression of STAT3 was also demonstrated using immunofluorescence in SMW-treated group. CONCLUSION: SMW showed significant anti-inflammatory and hypouricemic effects in a rat model of GA. It is an effective TCM formula for GA therapy.

Long non-coding RNA MAFG-AS1: A promising therapeutic target for human cancers.

Long non-coding RNAs (lncRNAs) are commonly known for their important characters in cancer progression. LncRNA MAFG-antisense 1 (AS1) (MAFG-AS1) has been discovered as a novel oncogenic lncRNA for several years. Accumulating data have demonstrated abnormal overexpression of MAFG-AS1 in various human cancers, including breast, bladder, liver, gastric, and lung. Importantly, through regulating various microRNAs and cell signaling pathways, MAFG-AS1 has been demonstrated to exhibit various biological effects, including proliferation, metastasis, and epithelial-mesenchymal transition (EMT). Meanwhile, abnormal overexpression of MAFG-AS1 is closely linked with histological grade, TNM stage, extensive depth of invasion, poor OS, and lymph node metastasis (LNM). In the present review, the authors summarized the previous studies on the biological properties, molecular mechanisms, and clinicopathological characters of MAFG-AS1 in human cancers. In summary, MAFG-AS1 is a promising prognostic biological marker and potential therapeutic target for cancer treatment.

Synergistic therapeutic potential of alpelisib in cancers (excluding breast cancer): Preclinical and clinical evidences.

The phosphoinositide 3-kinase (PI3K) signaling pathway is well-known for its important role in cancer growth, proliferation and migration. The activation of PI3K pathway is always connected with endocrine resistance and poor prognosis in cancers. Alpelisib, a selective inhibitor of PI3K, has been demonstrated to be effective in combination with endocrine therapy in HR+ PIK3CA-mutated advanced breast cancer in preclinical and clinical trials. Recently, the synergistic effects of alpelisib combined with targeted agents have been widely reported in PIK3CA-mutated cancer cells, such as breast, head and neck squamous cell carcinoma (HNSCC), cervical, liver, pancreatic and lung cancer. However, previous reviews mainly focused on the pharmacological activities of alpelisib in breast cancer. The synergistic therapeutic potential of alpelisib in other cancers has not yet been well reviewed. In this review, an extensive study of related literatures (published until December 20, 2022) regarding the anti-cancer functions and synergistic effects of alpelisib was carried out through the databases. Useful information was extracted. We summarized the preclinical and clinical studies of alpelisib in combination with targeted anti-cancer agents in cancer treatment (excluding breast cancer). The combinations of alpelisib and other targeted agents significantly improved the therapeutic efficacy both in preclinical and clinical studies. Unfortunately, synergistic therapies still could not effectively avoid the possible toxicities and adverse events during treatment. Finally, some prospects for the combination studies in cancer treatment were provided in the paper. Taken together, this review provided valuable information for alpelisib in preclinical and clinical applications.

The beneficial pharmacological effects and potential mechanisms of picroside II: Evidence of its benefits from in vitro and in vivo.

Picrorhiza kurroa, the dried rhizome of Picrorhiza kurroa Royle ex Benth, is a famous Chinese herb that has been traditionally used in China. Picroside II (PII), a glycoside derivative, is the main bioactive constituent of Picrorhiza kurroa. In the past several decades, bioactive components from Picrorhiza kurroa have attracted the attention of researchers due to their promising therapeutic effects. A large number of studies have demonstrated the therapeutic potential of PII for the prevention and treatment of some diseases, such as organic ischemia/reperfusion (I/R) injury, liver damage, inflammation, cancer metastasis and angiogenesis. In the present paper, we aimed to provide an overview of the pharmacology of PII, focusing on its anti-oxidant, anti-inflammatory and anti-apoptotic activities. Meanwhile, the plant tissue distribution and pharmacokinetic properties were also described. Due to its beneficial pharmacological effects in I/R injury, PII may serve as a promising therapeutic agent for organic I/R injury prevention.

Eupalinolide J induces apoptosis, cell cycle arrest, mitochondrial membrane potential disruption and DNA damage in human prostate cancer cells.

Eupalinolide J (EJ) is a new sesquiterpene lactone isolated from Eupatorium lindleyanum DC. In the present study, we investigated the anti-cancer activity of EJ on cell proliferation in human prostate cancer cells. The MTT results indicated that EJ showed marked anti-proliferative activity in PC-3 and DU-145 cells in a dose- and time-dependent manner. DAPI staining analysis demonstrated that this effect was mediated by induction of cell apoptosis. Flow cytometric analysis indicated a significant increase in apoptotic cells, cell cycle arrest at G0/G1 phase and disruption of mitochondrial membrane potential (MMP) after EJ treatment. Meanwhile, the activation of caspase-3 and caspase-9 was visibly observed. Furthermore, our results demonstrated that the expression levels of γH2AX, p-Chk1 and p-Chk2 were significantly up-regulated, suggesting the induction of DNA damage responses in EJ-treated prostate cancer cells. The above results indicated that EJ exhibited effective anti-cancer activity in vitro. It could be a promising candidate agent for the clinical treatment of prostate cancer.

Traditional Applications, Phytochemistry, and Pharmacological Activities of Eupatorium lindleyanum DC.: A Comprehensive Review.

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.

Alisol A Suppresses Proliferation, Migration, and Invasion in Human Breast Cancer MDA-MB-231 Cells.

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.

Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway.

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 IC50 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 via 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 vivo. In conclusion, we identified that EJ suppressed the growth of TNBC cells via targeting the STAT3 signaling pathway. These results strongly support that EJ is a promising therapeutic agent for TNBC.

Picroside II, an iridoid glycoside from Picrorhiza kurroa, suppresses tumor migration, invasion, and angiogenesis in vitro and in vivo.

Cancer is one of the leading causes of death worldwide. The development of novel anti-cancer agents from natural products is a promising approach to reduce cancer mortality. In this study, we investigated the anti-metastatic and anti-angiogenic activities of picroside II (PII) in human breast cancer cells both in vitro and in vivo. Our results demonstrated that PII significantly inhibited the migration and invasion of MDA-MB-231 cancer cells. With the treatment of PII, the activity of matrix metalloproteinase 9 (MMP-9) in MDA-MB-231 cancer cells was significantly inhibited both in vitro and in vivo. Meanwhile, PII showed effective anti-metastatic activity in an experimental lung metastasis model. Interestingly, cluster of differentiation 31 (CD31), a marker of angiogenesis, was significantly downregulated in the PII-treated tumor samples, indicating the anti-angiogenic activity of PII. Furthermore, we demonstrated that PII significantly inhibited the migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). The inhibition of MMP-9 activity in PII-treated HUVECs was also demonstrated. Finally, the suppression of angiogenesis by PII in the chick embryo chorioallantoic membrane (CAM) was observed. In conclusion, our results demonstrated that PII effectively inhibited the metastasis and angiogenesis of cancer cells both in vitro and in vivo, and thus, might be a novel candidate for cancer therapy.

Stephanthraniline A suppresses proliferation of HCT116 human colon cancer cells through induction of caspase-dependent apoptosis, dysregulation of mitochondrial function, cell cycle arrest and regulation of Akt/p38 signaling pathways.

Stephanthraniline A (STA) is a C21 steroidal aglycone isolated from the stem of Stephanotis mucronata (Blanco) Merr. that exerts growth inhibition in human colon cancer cells. However, the intracellular molecular mechanisms whereby this occurs have not been well characterized. In this study, we found that STA significantly inhibits the growth of HCT116 colon cancer cells in a time- and concentration-dependent manner. The inhibitory effect of STA on cell growth was related to the induction of apoptosis. Activated caspase-3, caspase-8 and caspase-9, along with a decreased Bcl-2/Bcl-x ratio and loss of mitochondrial membrane potential (Δψm), were observed in response to STA treatment. Furthermore, treatment of HCT116 cells with STA resulted in G0/G1 phase cell cycle arrest accompanied by decreased mRNA levels of cyclin-dependent kinase 4 (CDK4), p21 and c-myc. Additionally, the inhibition of Akt signaling and activation of p38 signaling were observed after treatment with STA in HCT116 cells. These findings indicate that STA inhibits HCT116 cell growth by promoting apoptosis, the dysregulation of mitochondrial function, and cell cycle arrest.

Polysaccharide from Phellinus Igniarius activates TLR4-mediated signaling pathways in macrophages and shows immune adjuvant activity in mice.

Polysaccharide from Phellinus igniarius (PPI) is known for its immune-regulating effect with low toxicity. Toll like receptor 4 (TLR4) is important in both innate and adaptive immune responses and considered to be a promising target for new immune adjuvants. In this study, PPI was investigated for its effect on activating TLR4 in RAW264.7 and peritoneal macrophages. The adjuvant potential of PPI was evaluated in OVA-immunized mice. The results showed PPI treatment significantly increased the secretion and the mRNA expression of both MyD88 dependent and TRIF dependent cytokines. IRAK-1, a key molecule on the downstream of MyD88, was polyubiquitinated while IRF-3, another key molecule on the downstream of TRIF, was phosphorylated obviously after the treatment of PPI. The phosphorylation of molecules involved in both NF-κB pathway and MAPK pathway were significantly up-regulated after PPI treatment. In addition, the effects of PPI on the macrophages almost completely disappeared after treating the cells with the TLR4 antagonist TAK-242. Further in vivo results showed PPI significantly increased the serum OVA-specific antibody and the OVA-specific spleen cell proliferation. Taken together, PPI can specifically stimulate TLR4 and activate both MyD88 and TRIF pathways. PPI has immune adjuvant activity and may become a new potential immune adjuvant.

F1012-2 inhibits the growth of triple negative breast cancer through induction of cell cycle arrest, apoptosis, and autophagy.

Sesquiterpene lactones (SLs) are plant-derived constituents that have been proved to have potential antitumour activity. However, the intracellular molecular targets of SLs and the underlying molecular mechanisms have not been well elucidated. Here, we report that F1012-2, a novel SL active fraction, isolated from Eupatorium lindleyanum DC., can significantly inhibit the growth of triple-negative breast cancer (TNBC) cells (MDA-MB-231 and MDA-MB-468) but has no obvious inhibitory effect on the growth of human mammary epithelial cells (MCF-10A). The related mechanisms on cell growth inhibition of F1012-2 were demonstrated by inducing apoptosis in a caspase-dependent manner through the intrinsic pathway and extrinsic pathway. F1012-2 could also activate autophagy in TNBC cells. Simultaneously, we found that F1012-2-induced apoptosis was enhanced by inhibition of autophagy. Furthermore, F1012-2 could induce cell cycle arrest at G2/M phase with decreasing expression of cyclin B1, cdc2, and upregulating p21, p-cdc2. Also, F1012-2 activated Akt and p38 signalling pathways. In vivo, F1012-2 exhibited a potential antitumour effect in MDA-MB-231 xenografts without apparent toxicity. Taken together, our results identified that F1012-2 inhibited cell growth via multiple signalling pathways in vitro and in vivo. These data suggest that F1012-2 may be a potential natural active fraction for the treatment of TNBC.

ZFP403, a novel tumor suppressor, inhibits the proliferation and metastasis in ovarian cancer.

OBJECTIVE: Zinc finger protein 403 (ZFP403) is located on human chromosome 17q12-21, the most common loss of heterozygosity regions for some oncogenes. However, the biological function of ZFP403 on tumor is controversial and its role in ovarian cancer remains unknown. This study aimed to investigate its biological function in ovarian cancer. METHODS: qRT-PCR and western blotting were first performed to detect the expression level of ZFP403 in ovarian cancer tissues and cells, respectively. The effect of ZFP403 on cell proliferation was determined by colony formation assays. Its effects on cell cycle were analyzed by flow cytometry and western blotting. Wound healing, Boyden chamber, western blotting and gelatin zymography assays were utilized to assess migration and invasion abilities of cells overexpressed with ZFP403. The xenograft model in nude mice was used to elucidate the role of ZFP403 on tumorigenesis in vivo. RESULTS: Compared with normal ovarian tissues and cells, significantly lower expression levels of ZFP403 were observed in ovarian cancer tissues and cells. Ectopic overexpression of ZFP403 in ovarian cancer cells dramatically suppressed cell proliferation by inducing cell cycle arrest at G2/M phase. Moreover, overexpression of ZFP403 in SK-OV3 cells inhibited cell migration and invasion. Xenograft study also demonstrated that overexpression of ZFP403 suppressed the tumor growth in vivo. CONCLUSION: The effects of ZFP403 on cell proliferation and metastasis suggest that it may serve as a tumor suppressor in ovarian cancer.

Arctigenin, a lignan from Arctium lappa L., inhibits metastasis of human breast cancer cells through the downregulation of MMP-2/-9 and heparanase in MDA-MB-231 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.

Eupalinolide O, a novel sesquiterpene lactone from Eupatorium lindleyanum DC., induces cell cycle arrest and apoptosis in human MDA-MB-468 breast cancer cells.

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-MB­468 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.

Targeting the ataxia telangiectasia mutated pathway for effective therapy against hirsutine-resistant breast cancer cells.

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.

Selective anticancer activity of hirsutine against HER2­positive breast cancer cells by inducing DNA damage.

Hirsutine is one of the major alkaloids isolated from plants of the Uncaria genus and is known for its cardioprotective, anti­hypertensive 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-MB­453 and BT474 cell lines. Conversely, HER2-negative/p53 wild­type 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 irinotecan­induced DNA damage response, our present results indicate the selective anticancer activity of hirsutine in HER2-positive breast cancer by inducing a DNA damage response.

Identification of Hirsutine as an anti-metastatic phytochemical by targeting NF-κB activation.

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 meta-stasis. 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.

Anticancer properties of 10-hydroxycamptothecin in a murine melanoma pulmonary metastasis model in vitro and in vivo.

Lung cancer, including lung metastatic cancer, remains one of the most difficult types of cancer to treat. Therefore, the search for new agents for its treatment is very important. 10-Hydroxycamptothecin (HCPT) was proved to have ideal anticancer activity in curing series cancer cells. In this study, the anticancer effect of HCPT on melanoma lung metastasis cancer was investigated by several administration routes, and whether the effect may be attributed to the induction of tumor cells apoptosis was determined. MTT assay results showed that HCPT exhibited selective cytotoxic activity against B16-F10 cells in a concentration- and time-dependent manner. Hoechst 33258 staining and transmission electron microscopy showed typical apoptotic morphology such as condensed chromatin, irregular nuclei, and apoptotic body formation. Flow cytometry analysis indicated a growth on apoptotic cells and a cell-cycle arrest in S phase after treatment with HCPT. In vivo melanoma pulmonary metastases were inhibited by treatment with HCPT. A more significant inhibition was observed if HCPT was administered by aerosol inhalation than that given by i.v. or i.p. administration. Thus, HCPT exhibited potential anticancer activity against B16-F10 cells in vitro and in vivo. However, the possible mechanisms involved still need to be investigated to explain this behavior.

Investigation on the morphological protective effect of 5-hydroxymethylfurfural extracted from wine-processed Fructus corni on human L02 hepatocytes.

AIM: To determine the mode of action of 5-hydroxymethylfurfural (5-HMF) extracted from wine-processed Fructus corni on hepatoprotective activities, the effects of 5-HMF on H(2)O(2)-induced human L02 hepatocytes injury was examined. MTHODS: Hepatocytes L02 injured by H(2)O(2) was treated by 5-HMF. The morphological changes of the cells were observed under inverted phase-contrast, fluorescence, and transmission electron microscopy and the activities of caspase-9 and caspase-3 were tested by enzyme-linked immunosorbent detector. RESULTS: It revealed that 5-HMF improved the morphology of H(2)O(2)-treated human L02 hepatocytes, and also inhibited the level of caspase-9 and caspase-3 of them. CONCLUSIONS: These results suggested a morphological hepatocyte protective effect and the anti-apoptosis mechanism by 5-HMF.