EMT - the dreaded Epithelial-Mesenchymal Transition
{Wiki: "The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells".
"EMT has been shown to be induced by androgen deprivation therapy in metastatic prostate cancer.[14] Activation of EMT programs via inhibition of the androgen axis provides a mechanism by which tumor cells can adapt to promote disease recurrence and progression."}
"This study provides evidence that melatonin inhibits migration and invasion through blocking multiple ... EMT-associated pathways"
Do you think 20 mg may be a cutoff threshold, below which melatonin has literally no effect on PCa?
I’ve read that long term use of melatonin can make bones more brittle, leading to more fractures in the elderly. Good to know that didn’t happen to you.
You are on a roll today Patrick! This is very interesting in providing a mechanism for melatonin's possible roll in suppressing EMT transition. This is one of the 10 (or12) "Hallmarks of Cancer", the stages of the development and progression of cancer into invasiveness and metastasis. Note that is not directly about treating advanced cancer. Metastatic PC has already gone through EMT and the other hallmarks. So while melatonin might also be somewhat beneficial in metastatic cancer (unclear), it should be more important at earlier non-metastatic stages to impair progression. I take melatonin, but like many here, have no idea what dosage could be beneficial and in what ways.
The other interesting note was the mention that androgen axis suppression actually increased EMT transition, a paradoxical counter to the overall benefits of androgen signaling regimens we rely upon?
The paper below indicates that doxycycline (part of the COC) protocol appears to be affective against gram negative bacteria, which the melatonin paper indicates are important for PCa invasion. The abstract of the paper below only mentions "promising chemotherapy effects" of doxycycline. Could the antibacterial effect be another reason why doxycycline might be useful against PCa?
Optimized doxycycline-loaded niosomal formulation for treatment of infection-associated prostate cancer: An in-vitro investigation
Author links open overlay panelImanAkbarzadeha1MohammadTavakkoli Yarakibc1MahsaBourbourdHassanNoorbazarganeAsemanLajevardifSeyedeh MaryamSadat ShilsargFatemehHeidarihSeyede MaryamMousaviani
•The doxycycline-loaded niosomes were optimized using a multi-objective response surface methodology.
•The optimized sample showed great storage stability.
•The antibacterial and anticancer effects of doxycycline were enhanced by niosomal formulation.
•The in-vitro cytotoxicity of the niosomal formulation was investigated on normal HEK293 cells and prostate cancer PC3 cells.
•The enhanced apoptosis of PC3 cells is due to the regulation of different gene expressions.
Abstract
Developing drug delivery systems with both antibacterial and anti-cancer effects is of importance in the treatment process of infection-associated cancers, especially prostate cancer. In this study, Span 60, Tween 60, and cholesterol were used to formulate doxycycline-loaded niosomes as a promising drug carrier system as either antibacterial or anticancer formulation. The formulation process was optimized by multi-objective response surface methodology (RSM), and then characterized. The developed niosomal formulation showed great storage stability for up to 2 weeks. In addition, they showed remarkable drug release in acidic solution (pH = 3) compared with physiological pH (7.4). The in-vitro performances of the as-developed niosomal formulations were investigated for two different applications: antibacterial and anticancer. The antibacterial properties of doxycycline-loaded niosome were investigated using different Gram-negative, and Gram-positive bacteria, where considerable (50–75%) decreases in MIC values were observed. Moreover, the niosomal formulation also possessed promising chemotherapy effects against prostate cancer cells (PC3) but enhanced biocompatibility against normal HEK293 cells. The enhanced chemotherapy effect was correlated to the regulation of different genes as well as changes in cell cycle of PC3 cells after treatment with the niosomal formulation. These carriers could be served as a potential drug delivery system for the treatment of prostate cancer.
Can someone help me understand this? So adt assists emt? And emt helps metastasis? So adt helps metastasis? I thought adt fights metastasis? Hope someone can help, my father is on zoladex by the way and it helped normalize his psa, he was also given melatonin lately to help sleep
Like you harley, a bit confused. I read the article 3x, and my head was spinning a bit. I wish this was a simple disease. The “Conclusion” was where the rubber meets the road. Yes on Melatonin. How much? How important after metastisis has occured? Bacterial infection blockade may be key in prohibiting some of the metastisis process!!Conclusion: This study provides evidence that melatonin inhibits migration and invasion through blocking multiple TLR4 downstream EMT-associated pathways both in LPS-stimulated and -unstimulated PCa cells. Our results provide new insights into the role of bacterial infection in PCa metastasis and a potential therapeutic agent.
Thank you, still confused though, but bery glad my fathers psa is back to normal range three months undee zoladex, its been years since his psa was sky high
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Imipramine Inhibits Migration and Invasion in Metastatic_Castration-Resistant_Prostate_Cancer
