The Wnt non-canonical signaling modulates cabazitaxel sensitivity in prostate cancer cells

Sennoune, Souad R.; Nelius, Thomas; Jarvis, Courtney; Pruitt, Kevin; Kottapalli, Kameswara Rao; Filleur, Stéphanie

doi:10.1371/journal.pone.0234078

Cited by 4 publications

(1 citation statement)

References 83 publications

(105 reference statements)

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“… 15 Moreover, the changes in the levels of various kinases, including PKC, are among the mechanisms involved in Cab response and long-term Cab-resistance of mCRPC cells. 22 As consistent with the findings, p-Nrf2 levels significantly decreased in all Cab-treated PC cells. However, this effect was more prominent in LNCaP mPC compared to LNCaP-HPR and C4–2 mCRPC cells.…”

Section: Discussionsupporting

confidence: 89%

Association between the apoptotic effect of Cabazitaxel and its pro-oxidant efficacy on the redox adaptation mechanisms in prostate cancer cells with different resistance phenotypes

Eryilmaz,

Egeli,

Cecener

2024

Cancer Biology & Therapy

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Redox adaptation causes poor prognosis by adapting cancer cells to excessive oxidative stress. Previously, we introduced an oxidative stress-resistant metastatic prostate cancer (mPC) model (LNCaP-HPR) that redox adaptation reduced the effect of Cabazitaxel (Cab), the last taxane-derivative for metastatic castration-resistant PC (mCRPC). Whereas, we investigated for the first time whether there is an association between the altered apoptotic effect and pro-oxidant efficacy of Cab on the redox adaptation in PC cells with different phenotypes, including LNCaP mPC, LNCaP-HPR, C4–2 mCRPC, and RWPE-1 cells. Cab was shown pro-oxidant efficacy proportionally with the apoptotic effect, more prominent in the less aggressive LNCaP cells, by increasing the endogenous ROS, mitochondrial damage, and inhibiting nuclear ROS scavengers, p-Nrf2 and HIF-1α. However, the pro-oxidant and apoptotic effect was lower in the LNCaP-HPR and C4–2 cells, indicating that the drug sensitivity of the cells adapted to survive with more ROS was reduced via altered regulation of redox adaptation. Additionally, unlike LNCaP, Cab caused an increase in the p-NF-κB activation, suggesting that the p-NF-κB might accompany maintaining survival with the increased ROS in the aggressive PC cells. Moreover, the cytotoxic and apoptotic effects of Cab were less on RWPE-1 cells compared to LNCaP but were closer to those on the more aggressive LNCaP-HPR and C4–2 cells, except for the changing pro-oxidant effect of Cab. Consequently, this study indicates the variable pro-oxidant effects of Cab on redox-sensitive proteins, which could be a target for improving Cab’s apoptotic effect more in aggressive PC cells.

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Section: Discussionsupporting

confidence: 89%