Cabazitaxel inhibits proliferation and potentiates the radiation response of U87MG glioblastoma cells

Abstract

Cabazitaxel is a second-generation semisynthetic taxane. The recognized anti-neoplastic effect of Cabazitaxel is cell cycle perturbation by inducing arrest at G2/M. Since glioblastoma tumors have a relatively high expression of P-gp, it is encouraging to find a treatment that is effective against these tumors. This study was conducted to examine the radiosensitizing potential of Cabazitaxel against U87MG cells. In order to evaluate the effect of Cabazitaxel, cells were treated with different concentrations of the drug at different time intervals and then cytotoxicity and cell cycle were assessed using MTT and flow cytometry assays, respectively. Annexin/PI and real-time polymerase chain reaction (PCR) assays were used to evaluate the extent of apoptosis. Cabazitaxel exerted a consistent G2/M arrest and resulted in a concentration- and time-dependent toxicity. Cabazitaxel enhanced the cytotoxicity response of U87MG cells to radiation. Apoptosis increased following Cabazitaxel-IR administration. At the same time, these results were further supported by apoptotic genes regulation. This study provides the first preclinical evidence supporting that Cabazitaxel can render U87MG cells more susceptible to the cytotoxicity of radiation and could potentially be administered in combination modalities as a promising cell cycle-specific radiosensitizer for the future steps of in vivo evaluation.

Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway

“…2B ). This observation is consistent with previous studies reporting that CBT causes G2/M cell cycle arrest in cancer cells [ 21 , 22 ]…”

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

“…: (a) The re-challenge with Cab chemotherapy was shown as working in CRPCa patients treated with > 10 cycles of Doc, with an acceptable risk of adverse effects burden [10][11][12]; (b) Cab at a higher initial dose demonstrated longer survival duration after treatment than a lower initial dose for Doc-resistant mCRPCa patients [13]; (c) Cab/prednisone administered weekly to unfit mCRPCa patients appeared to be as effective as classical standard 3-week scheme (TROPIC study) but with significantly lower toxicities and better tolerance [14]; and (d) the combination of Cab and abiraterone was found to have a manageable safety profile and showed antitumor activity in patients previously treated with Doc and abiraterone [15]. Furthermore, the promising therapeutic findings on Cab benefits (as mono-or combined therapies) in other types of cancers such as cisplatin-resistant germ cell tumor cells [16], breast cancer [17,18], sorafenib-resistant hepatocellular carcinomas [19], mCRPCa [20,21], cytarabine-resistant leukemia [22], glioblastoma [23] or gliomas [24] impel for more studies to understand Cab modes of action. Furthermore, the current growing interest in developing Cab-carrying nanovehicles (liposomes, micelles, and nanoparticles) to reduce Cab's side effects and increase its delivery and efficacy [17,18,[25][26][27][28][29][30][31][32][33][34] urges again for more investigations on Cab.…”