AI Article Synopsis
- Combination therapies using curcumin with cisplatin/carboplatin and gemcitabine can enhance cancer cell death in bladder cancer by inducing apoptosis and autophagy through suppression of Aurora A and activation of MEK/ERK.
- Animal studies showed that this combination therapy reduced tumor growth in mice, linked to specific changes in protein expression within tumors.
- Interestingly, while reduced Aurora A levels may not significantly impact drug sensitivity, high Aurora A expression in early-stage bladder cancer suggests that targeting it alongside promoting autophagy could improve treatment outcomes.
Article Abstract
Combination therapies to induce mixed-type cell death and synthetic lethality have the potential to overcome drug resistance in cancer. In this study, we demonstrated that the curcumin-enhanced cytotoxicity of cisplatin/carboplatin in combination with gemcitabine was associated with Aurora A suppression-mediated G2/M arrest, and thus apoptosis, as well as MEK/ERK-mediated autophagy in human bladder cancer cells. Animal study data confirmed that curcumin combined with cisplatin/gemcitabine reduced tumorigenesis of xenograft in mice and this phenomenon was associated with elevated expressions of p-ERK and reduced p-Aurora A in tumors. Gene analyses using data repositories further revealed that reduced Aurora A expression alone did not significantly elevate the sensitivity of human bladder carcinoma cells to these anticancer drugs. Unlike other major cancer types, human bladder urothelial carcinoma tissue coexpressed higher AURKA and lower MAP1LC3B than normal tissue, and reduced Aurora A and induction of autophagy have been clinically associated with a better prognosis in patients with early but not advanced stage bladder cancer. Therefore, our results suggest that treatment strategies can utilize the synthetic lethal pair to concurrently suppress oncogenic Aurora A and induce autophagy by coadministrating curcumin with anticancer drugs for early-stage bladder cancer with high expression of Aurora A.
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| http://dx.doi.org/10.1016/j.jnutbio.2023.109438 | DOI Listing |
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