RESUMO
Whole body vibration (WBV) is an innovative exercise mimetic that utilizes a vibrating platform to transmit mechanical vibrations throughout the body. WBV has been a popular area of research in recent years due to its potential physiological and therapeutic benefits in both health and disease. The utility of WBV is rooted in the various parameters (i.e., frequency, amplitude, duration) that affect the overall dose of vibration delivered to the body. Each type of WBV, coupled with these aforementioned parameters, should be considered when evaluating the use of WBV in the clinical setting. Thus, the purpose of this review is to provide an overview of recent literature detailing the different types of WBV, the various parameters that contribute to WBV efficacy, and the evidence of WBV in metabolic disease. A systematic search was conducted using Medline, Embase, Cochrane, CINAHL, and PubMed. All types of study designs were considered, with exclusions made for animal studies, duplicates, and study protocols without data. Thirty-four studies were included. In conclusion, as a modern exercise mimetic with therapeutic potential for metabolic diseases, understanding the interplay between the types and dosing of WBV is critical for determining its utility and efficacy. Further studies are certainly needed to elucidate the full therapeutic potential of WBV in metabolic diseases.
RESUMO
BACKGROUND: Colorectal cancer is the third largest cause of cancer-related mortality worldwide. Although current treatments with chemotherapeutics have allowed for management of colorectal cancer, additional novel treatments are essential. Intervening with the metabolic reprogramming observed in cancers called "Warburg Effect," is one of the novel strategies considered to combat cancers. In the metabolic reprogramming pathway, pyruvate dehydrogenase kinase (PDK1) plays a pivotal role. Identification and characterization of a PDK1 inhibitor is of paramount importance. Further, for efficacious treatment of colorectal cancers, combinatorial regimens are essential. To this end, we opted to identify a PDK1 inhibitor using computational structure-based drug design FINDSITEcomb and perform combinatorial studies with 5-FU for efficacious treatment of colorectal cancers. METHODS: Using computational structure-based drug design FINDSITEcomb, stearic acid (SA) was identified as a possible PDK1 inhibitor. Elucidation of the mechanism of action of SA was performed using flow cytometry, clonogenic assays. RESULTS: When the growth inhibitory potential of SA was tested on colorectal adenocarcinoma (DLD-1) cells, a 50% inhibitory concentration (IC50) of 60 µM was recorded. Moreover, SA inhibited the proliferation potential of DLD-1 cells as shown by the clonogenic assay and there was a sustained response even after withdrawal of the compound. Elucidation of the mechanism of action revealed, that the inhibitory effect of SA was through the programmed cell death pathway. There was increase in the number of apoptotic and multicaspase positive cells. SA also impacted the levels of the cell survival protein Bcl-2. With the aim of achieving improved treatment for colorectal cancer, we opted to combine 5-fluorouracil (5-FU), the currently used drug in the clinic, with SA. Combining SA with 5-FU, revealed a synergistic effect in which the IC50 of 5-FU decreased from 25 to 6 µM upon combination with 60 µM SA. Further, SA did not inhibit non-tumorigenic NIH-3T3 proliferation. CONCLUSIONS: We envision that this significant decrease in the IC50 of 5-FU could translate into less side effects of 5-FU and increase the efficacy of the treatment due to the multifaceted action of SA. The data generated from the current studies on the inhibition of colorectal adenocarcinoma by SA discovered by the use of the computational program as well as synergistic action with 5-FU should open up novel therapeutic options for the management of colorectal adenocarcinomas.