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Inhibition of 5-lipoxygenase downregulates stemness

pjoshea13 profile image
4 Replies

New study below.

Very important, if true. & we have a remedy:

5-LOXIN from Boswellia (frankincense).

(Nalakrats has mentioned its importance.}

5-loxin.com

swansonvitamins.com/swanson...

"The CD44 (+), CD133 (+) cell subpopulations were isolated from human prostate tumors which exhibit stem-like properties showing therapeutic-resistance, capacity of self-renewal, and exact recapitulation of the original tumor in vivo."

"... inhibition of 5-lipoxygenase (5-Lox) by shRNA or MK591 dramatically kills PCSC by inducing apoptosis, suggesting that 5-Lox plays an essential role in the survival of" prostate cancer stem cells.

-Patrick

ncbi.nlm.nih.gov/pubmed/278...

Oncotarget. 2016 Nov 17. doi: 10.18632/oncotarget.13422. [Epub ahead of print]

Inhibition of 5-lipoxygenase downregulates stemness and kills prostate cancer stem cells by triggering apoptosis via activation of c-Jun N-terminal kinase.

Sarveswaran S1, Varma N1, Morisetty S1, Ghosh J1.

Author information

1Vattikuti Urology Institute and Josephine Ford Cancer Center, Henry Ford Health System, Detroit, MI 48202, USA.

Abstract

The cancer stem cell (CSC) concept suggests that neoplastic clones are maintained exclusively by a rare group of cells possessed with stem cell properties. CSCs are characterized by features that include self-renewal, pluripotency and tumorigenicity, and are thought to be solely responsible for tumor recurrence and metastasis. A hierarchically organized CSC model is becoming increasingly evident for various types of cancer, including prostate cancer. The CD44 (+), CD133 (+) cell subpopulations were isolated from human prostate tumors which exhibit stem-like properties showing therapeutic-resistance, capacity of self-renewal, and exact recapitulation of the original tumor in vivo. Thus, an important challenge is to find measures to eliminate these cancer stem cells, which will stop tumor growth and prevent disease-recurrence. However, knowledge about molecular features critical for the survival of prostate cancer stem cells (PCSC) is meager. Here we report that inhibition of 5-lipoxygenase (5-Lox) by shRNA or MK591 dramatically kills PCSC by inducing apoptosis, suggesting that 5-Lox plays an essential role in the survival of PCSC. Interestingly, MK591 treatment decreases protein levels and inhibits transcriptional activities of Nanog and c-Myc. Since Nanog and c-Myc play important roles as stemness factors, our findings indicate that the 5-Lox activity plays a causal role in maintaining prostate cancer stemness via regulation of Nanog and c-Myc, and suggest that further exploration of 5-Lox-mediated signaling in PCSC may lead to development of novel, target-based, durable strategies to effectively block development and growth of prostate tumors, and prevent prostate cancer recurrence.

KEYWORDS:

5-lipoxygenase; MK591; apoptosis; c-Myc; prostate cancer stem cells

PMID: 27880719 DOI: 10.18632/oncotarget.13422

[PubMed - as supplied by publisher]

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4 Replies
Daddyishealing profile image
Daddyishealing

Does this mean the supplement 5 loxin should not be taken because 5 lox "plays a crucial role in pcsc? "I apologize for my confusion

pjoshea13 profile image
pjoshea13 in reply toDaddyishealing

5-LOXIN inhibits 5-LOX, so it is a very good thing.

-Patrick

Daddyishealing profile image
Daddyishealing in reply topjoshea13

Ty I originally thought that but got confused, the medical diction can be confusing . I could not find a dosage equivalent to the study. if anyone knows let me know. very promising study thanks for sharing Patrick

Frank_M profile image
Frank_M

Hi Patrick.

Many thanks for sharing. An important observation! There is evidence I've been investigating that Protease Inhibitors, esp Lopinavir, also attack stem cells. Unless you can kill stem cells the tumour will relapse (IMHO).

~ Frank

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