Kaempferol, which is isolated from several natural plants, is a polyphenol belonging to the subgroup of flavonoids. Kaempferol exhibits various pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. In this study, kaempferol can significantly inhibit the invasion and migration of 786-O renal cell carcinoma (RCC) without cytotoxicity. We examined the potential mechanisms underlying its anti-invasive activities on 786-O RCC cells. Western blot was performed, and the results showed that kaempferol attenuates the manifestation of metalloproteinase-2 (MMP-2) protein and activity. The inhibitive effect of kaempferol on MMP-2 may be attributed to the downregulation of phosphorylation of Akt and focal adhesion kinase (FAK). By examining the SCID mice model, we found that kaempferol can safely inhibit the metastasis of the 786-O RCC cells into the lungs by about 87.4% as compared to vehicle treated control animals. In addition, the lung tumor masses of mice pretreated with 2-10 mg/kg kaempferol were reduced about twofold to fourfold. These data suggested that kaempferol can play a promising role in tumor prevention and cancer metastasis inhibition.

N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing.

The variation in the mortality-to-incidence ratio (MIR) between countries and genders reflects the complex etiology and intervention of bladder cancer. In this study, we investigated the MIR variation between genders and health care disparities among countries. Cancer incidence and mortality were obtained from the GLOBOCAN 2012 database. The ranking and the total expenditure on health of countries were obtained from the World Health Organization. Linear regression was used to estimate the significance between variables. We estimated the role of MIRs from 33 countries. Bladder cancer incidence and mortality rates were higher in more developed regions, Europe, and the Americas. The MIRs were higher in less developed regions. Analysis according to country revealed Germany to have the lowest MIR. High relative MIRs (female MIR/male MIR) for bladder cancer were noted in many developed countries. A correlation between MIR and health care disparities among countries was indicated by a significant association between the World Health Organization ranking and total expenditure on health/GDP with the MIR and relative MIR. Low bladder cancer MIR is prone to be more prevalent in countries with good health care system.

Fisetin, a natural flavonoid, is known to have anticarcinogenic effects against several cancers, but its role in mediating renal cell carcinoma (RCC) progression has not been delineated. Cell viability, cytotoxicity, and cell cycle distribution were measured using the 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and propidium iodide staining with flow cytometry. The in vitro migration and invasion assay was used to examine in vivo cell migration and invasion. Human protease antibody array analysis was conducted with cell migration/invasion-related proteins. Western blotting and quantitative reverse transcription polymerase chain reaction were used for assessing protein expression related to the cell cycle, cell invasion, and mitogen-activated protein kinase (MAPK) signaling pathway. We found that fisetin significantly inhibited cell viability through cell cycle arrest in the G2/M phase, in addition to downregulating cyclin D1 and upregulating p21/p27. Fisetin inhibited the migration and invasion of human RCC cells through the downregulation of CTSS and a disintegrin and metalloproteinase 9 (ADAM9). Fisetin also upregulated ERK phosphorylation in 786-O and Caki-1 cells. Furthermore, treatment with a MEK inhibitor (UO126) reduced the inhibitory effects of fisetin on the metastasis of RCC cells through the ERK/CTSS/ADAM9 pathway. Fisetin inhibits proliferation and metastasis of RCC cells by downregulating CTSS and ADAM9 through the MEK/ERK signaling pathway. These findings indicate that fisetin is a promising antitumor agent against RCC.

Background: Colorectal cancer (CRC) is the third commonly diagnosed cancer worldwide. Recurrence of CRC (Re) and onset of a second primary malignancy (SPM) are important indicators in treating CRC, but it is often difficult to predict the onset of a SPM. Therefore, we used mechanical learning to identify risk factors that affect Re and SPM.

Phytochemicals represent an important source of novel anticancer and chemotherapeutic agents. Thymoquinone (TQ) is the major bioactive phytochemical derived from the seeds of Nigella sativa and has shown potent anticancer activities. In this study, we aimed to investigate the anticancer activity of Thymoquinone on the human renal carcinoma cell 786-O-SI3 and the underlying mechanism. By using cell proliferation assay, wound healing, and invasion assay, we found that Thymoquinone did not affect the viability of 786-O-SI3 and human kidney-2, but clearly inhibited the migration and invasion of 786-O-SI3. Further zymography and immunoblotting analysis showed that Thymoquinone downregulated the activity and expression of matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA) and attenuated the adhesion of 786-O-SI3 to type I and type IV collagen. Kinase cascade assay indicated that Thymoquinone inhibited the phosphorylation of phosphatidylinositol 3-kinase, Akt, Src, and Paxillin. In addition, Thymoquinone also decreased the level of fibronectin, N-cadherin, and Rho A. In parallel, Thymoquinone dose-dependently suppressed the transforming growth factor (TGF)-β-promoted u-PA activity and expression, as well as the cell motility and invasion of 786-O-SI3. Furthermore, tumor xenograft model revealed that Thymoquinone in vivo inhibited the 786-O-SI3 metastasizing to the lung. Collectively, these findings indicate that Thymoquinone inhibits the metastatic ability of 786-O-SI3, suggesting that Thymoquinone might be beneficial to promote the chemotherapy for renal cell carcinoma.