Stage-Specific Effect of Inositol Hexaphosphate on Cancer Stem Cell Pool during Growth and Progression of Prostate Tumorigenesis in TRAMP Model

Herein, we assessed the stage-specific efficacy of inositol hexaphosphate (IP6, phytic acid), a bioactive food component, on prostate cancer (PCa) growth and progression in a transgenic mouse model of prostate cancer (TRAMP). Starting at 4, 12, 20, and 30 weeks of age, male TRAMP mice were fed eithe...

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Published inCancers Vol. 14; no. 17; p. 4204
Main Authors Raina, Komal, Kandhari, Kushal, Jain, Anil K, Ravichandran, Kameswaran, Maroni, Paul, Agarwal, Chapla, Agarwal, Rajesh
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 30.08.2022
MDPI
Subjects
Adenocarcinoma
Animals
Antibodies
Cancer cells
cancer stem cells
Care and treatment
Cell culture
Cell self-renewal
chemoprevention
Drinking water
Health aspects
Inositol
inositol hexaphosphate
Malignancy
Medical research
Metastasis
Phytic acid
Prostate cancer
Prostatic intraepithelial neoplasia
Software
Stem cell transplantation
Stem cells
TRAMP
Transgenic mice
Tumorigenesis
United States
St Louis Missouri
United States > US
prostate cancer
TRAMP
chemoprevention
cancer stem cells
inositol hexaphosphate
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Summary:Herein, we assessed the stage-specific efficacy of inositol hexaphosphate (IP6, phytic acid), a bioactive food component, on prostate cancer (PCa) growth and progression in a transgenic mouse model of prostate cancer (TRAMP). Starting at 4, 12, 20, and 30 weeks of age, male TRAMP mice were fed either regular drinking water or 2% IP6 in water for ~8-15 weeks. Pathological assessments at study endpoint indicated that tumor grade is arrested at earlier stages by IP6 treatment; IP6 also prevented progression to more advanced forms of the disease (~55-70% decrease in moderately and poorly differentiated adenocarcinoma incidence was observed in advanced stage TRAMP cohorts). Next, we determined whether the protective effects of IP6 are mediated via its effect on the expansion of the cancer stem cells (CSCs) pool; results indicated that the anti-PCa effects of IP6 are associated with its potential to eradicate the PCa CSC pool in TRAMP prostate tumors. Furthermore, in vitro assays corroborated the above findings as IP6 decreased the % of floating PC-3 prostaspheres (self-renewal of CSCs) by ~90%. Together, these findings suggest the multifaceted chemopreventive-translational potential of IP6 intervention in suppressing the growth and progression of PCa and controlling this malignancy at an early stage.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14174204