Castration-resistant prostate cancer (CRPC) frequently develops after initial standard radiation and androgen deprivation therapy, leaving patients with limited further treatment options. Androgen receptor (AR) is a transcription factor that plays a key role in the initiation and progression of prostate cancer. p53, a major tumor suppressor that is rarely mutated in early-stages of prostate cancer, is often deregulated during prostate cancer progression. Here, we report an unusual co-amplification of MDM2 and MDMX, two crucial negative regulators of p53, in CRPC datasets. We demonstrate that combinatorial inhibition of MDM2 and MDMX, with nutlin-3 and NSC207895 respectively, has a profound inhibitory effect on cell proliferation of androgen-responsive, wild-type TP53 gene carrying prostate cancer cells LNCaP and 22Rv1. We further show that the combinatorial inhibition of MDM2 and MDMX not only activates p53, but also decreases cellular levels of AR and represses its function. Additionally, co-expression of MDM2 and MDMX stabilizes AR. Together, our results indicate that combinatorial inhibition of MDM2 and MDMX may offer a novel compelling strategy for prostate cancer therapy.

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In recent years, amniotic fluids have gained attention in cancer research. They have an influential role in protecting embryos against several anomalies. Chick early amniotic fluid (ceAF)—amniotic fluid isolated from growing chicken—has been used in many other studies, including myocardial infarctions and skin regeneration. In this study, we employed ceAF’s promising therapeutic applications against tumorigenesis in both in vitro and in vivo studies. We selected three robust proliferating tumor cell lines: BCaP37, MCF7, and RKO. We found that selective dosage is required to obtain maximum impact to deter tumorigenesis. ceAF not only disrupted the uniform colonies of tumor cell lines via disturbing mitochondrial transmembrane potential, but also arrested many cells at growing G1 state via working agonistically with aphidicolin. The significant inhibition of tumor metastasis by ceAF was indicated by in vivo models. This leads to apoptosis analysis as verified by annexin-V staining stays and immunoblotting of critical proteins as cell cycle meditators and apoptosis regulators. Not only on the protein level, but we also tested ceAF’s therapeutic potentials on mRNA levels as indicated by quantitative real-time PCR summarizing the promising role of ceAF in deterring tumor progression. In conclusion, our study reveals the potent role of ceAF against tumorigenesis in breast cancer and colon carcinoma. Further studies will be required to determine the critical components present in ceAF and its purification to narrow down this study.