Aldehyde dehydrogenase activity in xenografted human brain tumor in nude mice. Preliminary results in human glioma biopsies

Abstract

ALDH activity measured fluorimetrically using a high concentration of aliphatic aldehyde as substrate was studied in human glioblastomas grafted in nude mice. Compared with normal brain, ALDH activity is significantly increased in malignant glioma tissue, especially in the cytosolic subcellular fraction. Correlatively, in comparison with normal brain tissue, MDA levels were significantly reduced in whole homogenates and in cytosolic fractions of xenografted glioblastoma tissue. Preliminary results concerning human malignant glioma biopsies are in good agreement with our experimental data. In view of previous works, these results suggest a relationship between alterations in ALDH iso-enzymes activities and cytosolic aldehyde concentrations with respect to normal or tumoral cell growth.

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

“…Disulfiram exerts significant anticancer activity in multiple contexts [ 112 - 118 ]. Particularly the stem cell sub-population of glioblastoma are ALDH positive [ 97 , 98 , 120 - 123 ], and susceptible to inhibition by disulfiram [ 97 , 98 , 100 , 120 - 124 ]. We have increasing pre-clinical evidence that disulfiram, an old and inexpensive drug in continuous use for 6 decades in alcohol aversion therapy exerts significant anticancer activity [ 104 , 112 - 118 ].…”

“…5. Both disulfiram [ 98 , 100 , 121 - 124 ] and nelfinavir and other HSP90 inhibitors [ 294 - 296 ] have shown specificity in inhibiting cancer stem cell function.…”

Aldehyde dehydrogenase and HSP90 co-localize in human glioblastoma biopsy cells

“…Already in 1990 both human glioblastoma growing in nude mice and human glioblastoma biopsy tissue were shown to have greatly increased ALDH activity [31]. Then in 2010 ALDH was shown to facilitate clonal sphere formation in established glioblastoma cell lines [16].…”

Stem Cells in Brain Tumour Development and Therapy- Two-Sides of the Same Coin

“…Subsequently, the identification of putative NSCs in the central nervous system was reported by Corti et al who showed that SSC lo ALDH br cells obtained from murine adult and embryonic neurospheres cells were capable of self-renewal and multi-potent differentiation in vitro and vivo 79 . The enhanced functional activity of ALDH was not only observed in the progenitor cells in the hematopoietic and central nervous system, [80][81][82] but also in human malignancies such as cancers of the lung 83,84 , breast 85 , colon 86 , liver 87 , brain 88,89 , and head and neck squamous cells. 90 It was also associated with disease progression 91 , metastasis [92][93][94] and poor clinical outcome 93,[95][96][97][98] .…”