New insights into lipid metabolism and prostate cancer (Review)

Zhang, Zhengliang; Wang, Weixi; Kong, Piaoping; Feng, Kangle; Liu, Chunhua; Sun, Tao; Sang, Yiwen; Duan, Xin; Tao, Zhihua; Liu, Weiwei

doi:10.3892/ijo.2023.5522

Cited by 6 publications

(1 citation statement)

References 165 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, several studies show that prostate cancer cells and PC-3 cells, in particular, show different lipid profiles [ 49 , 50 ]. Moreover, in a previous study, we showed that the membrane and cell viscosity of PC-3 were different from those of the non-tumor control [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Carrier–Tumor Cell Membrane Interactions for Optimized Delivery of a Promising Drug, 4(RS)-4-F4t-Neuroprostane

Abawi,

Thomann,

Lollo

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

Nanomedicines engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or a short half-life, are targeted towards their cellular destination either passively or through various elements of cell membranes. The differences in the physicochemical properties of the cell membrane between tumor and nontumor cells have been reported, but they are not systematically used for drug delivery purposes. Thus, in this study, a new approach based on a match between the liposome compositions, i.e., membrane fluidity, to selectively interact with the targeted cell membrane was used. Lipid-based carriers of two different fluidities were designed and used to deliver 4(RS)-4-F4t-Neuroprostane (F4t-NeuroP), a potential antitumor molecule derived from docosahexaenoic acid (DHA). Based on its hydrophobic character, F4t-NeuroP was added to the lipid mixture prior to liposome formation, a protocol that yielded over 80% encapsulation efficiency in both rigid and fluid liposomes. The presence of the active molecule did not modify the liposome size but increased the liposome negative charge and the liposome membrane fluidity, which suggested that the active molecule was accommodated in the lipid membrane. F4t-NeuroP integration in liposomes with a fluid character allowed for the selective targeting of the metastatic prostate cell line PC-3 vs. fibroblast controls. A significant decrease in viability (40%) was observed for the PC-3 cancer line in the presence of F4t-NeuroP fluid liposomes, whereas rigid F4t-NeuroP liposomes did not alter the PC-3 cell viability. These findings demonstrate that liposomes encapsulating F4t-NeuroP or other related molecules may be an interesting model of drug carriers based on membrane fluidity.

show abstract

Section: Discussionmentioning

confidence: 99%

Carrier–Tumor Cell Membrane Interactions for Optimized Delivery of a Promising Drug, 4(RS)-4-F4t-Neuroprostane

Abawi,

Thomann,

Lollo

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

show abstract

Dual targeting of the androgen receptor and PI3K/AKT/mTOR pathways in prostate cancer models improves antitumor efficacy and promotes cell apoptosis

Sugawara,

Nevedomskaya,

Heller

et al. 2024

Molecular Oncology

View full text Add to dashboard Cite

Prostate cancer is a frequent malignancy in older men and has a very high 5‐year survival rate if diagnosed early. The prognosis is much less promising if the tumor has already spread outside the prostate gland. Targeted treatments mainly aim at blocking androgen receptor (AR) signaling and initially show good efficacy. However, tumor progression due to AR‐dependent and AR‐independent mechanisms is often observed after some time, and novel treatment strategies are urgently needed. Dysregulation of the PI3K/AKT/mTOR pathway in advanced prostate cancer and its implication in treatment resistance has been reported. We compared the impact of PI3K/AKT/mTOR pathway inhibitors with different selectivity profiles on in vitro cell proliferation and on caspase 3/7 activation as a marker for apoptosis induction, and observed the strongest effects in the androgen‐sensitive prostate cancer cell lines VCaP and LNCaP. Combination treatment with the AR inhibitor darolutamide led to enhanced apoptosis in these cell lines, the effects being most pronounced upon cotreatment with the pan‐PI3K inhibitor copanlisib. A subsequent transcriptomic analysis performed in VCaP cells revealed that combining darolutamide with copanlisib impacted gene expression much more than individual treatment. A comprehensive reversal of the androgen response and the mTORC1 transcriptional programs as well as a marked induction of DNA damage was observed. Next, an in vivo efficacy study was performed using the androgen‐sensitive patient‐derived prostate cancer (PDX) model LuCaP 35 and a superior efficacy was observed after the combined treatment with copanlisib and darolutamide. Importantly, immunohistochemistry analysis of these treated tumors showed increased apoptosis, as revealed by elevated levels of cleaved caspase 3 and Bcl‐2‐binding component 3 (BBC3). In conclusion, these data demonstrate that concurrent blockade of the PI3K/AKT/mTOR and AR pathways has superior antitumor efficacy and induces apoptosis in androgen‐sensitive prostate cancer cell lines and PDX models.

show abstract