Abstract 3475: CYP3A5 inhibitor bergamottin present in grape fruit extract blocks prostate cancer cell growth
| Autor: | Ranjana Mitra, Opalina Vetrichelvan, Priyatham Gorjala, Oscar B. Goodman |
|---|---|
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Cancer Research. 80:3475-3475 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Background: Previous research has revealed that the androgen receptor (AR), which upon activation goes to the nucleus, is the driving force of prostate cancer growth. Once activated, AR promotes transcription of genes responsible for promoting cancer growth. Previous studies have shown that inhibition of CYP3A5 blocks the activation process of the AR. CYP3A5 is a liver enzyme and together with CYP3A4 processes 50% of all commonly prescribed drugs. CYP3A5 is the extrahepatic form expressed in both normal and malignant prostate. Bergamottin, a compound found in grapefruit juice, is a known CYP3A4/5 inhibitor. Based on CYP3A5's ability to regulate AR activation, we tested the effects of bergamottin on AR activation to see if the compound can be utilized as a dietary supplement to reduce prostate cancer growth. Methods: Western blotting, cell fractionation, and immunofluorescence were used to observe the effects of bergamottin on AR, amount of AR in nucleus/cytoplasm, and cellular localization of AR, respectively. MTT based cell growth measurement was used to see how prostate cancer cell growth was affected by bergamottin. Results: Cell growth assay revealed that bergamottin reduced prostate cancer cell growth. The IC50 for LNCaP cells was observed to be 2.4 μM. Growth of RWPE1 cells (non transformed prostate epithelium) was not effected at the same concentration of bergamottin. Western blot analysis showed that total AR protein expression was downregulated in the bergamottin treated LNCaP and MDAPCa2b cells. Cell fractionation assay revealed that bergamottin significantly reduced nuclear AR after DHT induction compared to non-treated cells. Immunofluorescence assay confirmed reduced nuclear AR in the bergamottin treated LNCaP and MDAPCa2b cells. Furthermore, bergamottin reduced PSA levels both inside the cells and in the growth media indicating that it inhibits AR downstream signaling. Conclusion: Our results concluded that bergamottin successfully blocked AR activation and downstream signaling, and consequently slowed down prostate cancer cell growth. The implication of this experiment is the potential use of bergamottin as a food supplement alongside other prostate cancer treatments in order to aid in blocking prostate cancer growth. Citation Format: Opalina Vetrichelvan, Priyatham Gorjala, Oscar Goodman Jr, Ranjana Mitra. CYP3A5 inhibitor bergamottin present in grape fruit extract blocks prostate cancer cell growth [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3475. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|