3-5-bis(2-fluorobenzylidene)piperidin-4-one and Colorectal-Neoplasms

3-5-bis(2-fluorobenzylidene)piperidin-4-one has been researched along with Colorectal-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for 3-5-bis(2-fluorobenzylidene)piperidin-4-one and Colorectal-Neoplasms

ArticleYear
Impressive Suppression of Colon Cancer Growth by Triple Combination SN38/EF24/Melatonin: "Oncogenic"
    Anticancer research, 2017, Volume: 37, Issue:10

    The study aimed to investigate the effect of multi-targeted combinations (SN38/EF24; SN38/EF24/melatonin) on the growth of colon cancer in experimental animals and their impact on the ratio "oncogenic"/"onco-suppressive" reactive oxygen species (ROS) - a crucial factor for triggering carcinogenesis, as well as for development of effective therapeutic strategies.. The experiments were conducted on colon cancer-grafted mice - non-treated, SN38/EF24-treated and SN38/EF24/melatonin-treated within 22 days. The balance between different types of ROS was measured in vivo by nitroxide-enhanced magnetic resonance imaging (MRI), as well as on isolated tissue specimens by conventional analytical tests.. Both combinations significantly suppressed the tumor growth. Impressive anticancer effect was observed in SN38/EF24/melatonin-treated mice - almost complete destruction of the tumor. Both types of ROS (superoxide and hydroperoxides) were elevated in cancer, but the MRI data suggest that the ratio between them tends towards superoxide. SN38/EF24 decreased the level of superoxide, but did not affect the level of hydroperoxides in the cancerous tissue, while SN38/EF24/melatonin decreased the level of superoxide below the control and increased significantly the level of hydroperoxides.. The most important observations are that: (i) colon cancer was characterized by a vicious cycle, that ensures a permanent domination of "oncogenic" ROS (as superoxide) over "onco-suppressive" ROS (as hydrogen peroxide); (ii) the anticancer effect of the triple combination EF24/SN38/melatonin was accompanied by decreasing "oncogenic" and increasing "onco-suppressive" ROS; (iii) the ratio between both types of ROS could be a new onco-target for combined therapy; and (iv) nitroxide-enhanced MRI is a valuable tool for analyzing of this ratio.

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzylidene Compounds; Camptothecin; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Hydrogen Peroxide; Irinotecan; Magnetic Resonance Imaging; Male; Melatonin; Mice, Inbred BALB C; Mice, Nude; Oncogenes; Oxidative Stress; Piperidones; Reactive Oxygen Species; Signal Transduction; Superoxides; Time Factors; Tumor Burden

2017
Curcumin analog EF24 induces apoptosis via ROS-dependent mitochondrial dysfunction in human colorectal cancer cells.
    Cancer chemotherapy and pharmacology, 2016, Volume: 78, Issue:6

    Colorectal cancer is the most commonly diagnosed malignancy with high mortality rates worldwide. Improved therapeutic strategies with minimal adverse side effects are urgently needed. In this study, the anti-tumor effects of EF24, a novel analog of the natural compound curcumin, were evaluated in colorectal cancer cells.. The anti-tumor activity of EF24 on human colon cancer lines (HCT-116, SW-620, and HT-29) was determined by measures of cell cycle arrest, apoptosis, and mitochondrial function. The contribution of ROS in the EF24-induced anti-tumor activity was evaluated by measures of H. The findings indicated that EF24 treatment dose-dependently inhibited cell viability and caused cell cycle arrest at G2/M phase in all the tested colon cancer cell lines. Furthermore, we demonstrated that EF24 treatment induced apoptosis effectively via enhancing intracellular accumulation of ROS in both HCT-116 and SW-620 cells, but with moderate effects in HT-29 cells. We found that EF24 treatment decreased the mitochondrial membrane potential in the colon cancer cells, leading to the release of mitochondrial cytochrome c. Also, EF24 induced activation of caspases 9 and 3, causing decreased Bcl-2 protein expression and Bcl-2/Bax ratio. Pretreatment with NAC, a ROS scavenger, abrogated the EF24-induced cell death, apoptosis, cell cycle arrest, and mitochondrial dysfunction, suggesting an upstream ROS generation which was responsible for the anticancer effects of EF24.. Our findings support an anticancer mechanism by which EF24 enhanced ROS accumulation in colon cancer cells, thereby resulting in mitochondrial membrane collapse and activated intrinsic apoptotic signaling. Thus, EF24 could be a potential candidate for therapeutic application of colon cancer.

    Topics: Antineoplastic Agents; Apoptosis; Benzylidene Compounds; Caspases; Cell Line, Tumor; Cell Survival; Colorectal Neoplasms; Curcumin; Cytochromes c; Humans; Membrane Potential, Mitochondrial; Mitochondria; Piperidones; Reactive Oxygen Species

2016