Effects of Hypoxia on Ascorbic Acid-Mediated Cytotoxicity in Prostate Cancer In Vitro
| dc.contributor.advisor | Bressler, Joseph | |
| dc.creator | Ramezani, Ida | |
| dc.date.accessioned | 2022-08-01T15:21:25Z | |
| dc.date.available | 2022-08-01T15:21:25Z | |
| dc.date.created | 2022-05 | |
| dc.date.issued | 2022-05-05 | |
| dc.date.submitted | May 2022 | |
| dc.date.updated | 2022-08-01T15:21:25Z | |
| dc.description.abstract | Prostate cancer has the highest incidence of cancer and second highest number of deaths from cancer in men in the United States. It is the most diagnosed cancer in men globally. Age is the primary risk factor for prostate cancer etiology. Prostate cancers are androgen receptor- dependent and are treated with androgen- deprivation therapies. Some patients develop androgen receptor- independent characteristics that allow for metastasis. Around 10-20% of this subset progress to castration resistant prostate cancer. These patients typically have a poorer prognosis and are treated with nonspecific chemotherapeutics. Ascorbic acid has been utilized in clinical trials as a natural chemotherapeutic and chemotherapeutic adjuvant to improve patient prognosis. Ascorbic acid decreases cell viability through the production of hydrogen peroxide via the Fenton reaction that requires iron and oxygen. Our goal was to investigate the effects of the tumor microenvironment on ascorbic acid- mediated cell viability. Specifically, our focus was on ascorbic acid- mediated response to hypoxia. Prostate cancer cell lines, PC-3 and DU-145, were utilized. Non-tumorigenic cell lines, RWP and 957-AR, were also utilized. Cell viability was measured using an MTT assay. To measure extracellular hydrogen peroxide, the AmplexTM Red Peroxidase assay was conducted. Results demonstrated that hypoxia attenuates ascorbic acid- mediated cell viability in cancer cells. The effect of hypoxia was not observed in non-tumorigenic cell lines. The effects of ascorbic acid were mediated through the production of hydrogen peroxide that required only the chemicals in the media. Cells appear to either degrade hydrogen peroxide through enzymes or inhibit formation of hydrogen peroxide at low doses of ascorbic acid. Further investigation on the mechanism of ascorbic acid and hydrogen peroxide in the cellular environment is needed. The nature of the tumor microenvironment is also pivotal in this understanding to improve natural adjuvants and treatments for prostate cancer. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | http://jhir.library.jhu.edu/handle/1774.2/67390 | |
| dc.language.iso | en_US | |
| dc.publisher | Johns Hopkins University | |
| dc.publisher.country | USA | |
| dc.subject | prostate cancer | |
| dc.subject | hypoxia | |
| dc.subject | ascorbic acid | |
| dc.subject | vitamin c | |
| dc.subject | ascorbate | |
| dc.subject | tumor microenvironment | |
| dc.subject | cell viability | |
| dc.subject | reactive oxygen species | |
| dc.title | Effects of Hypoxia on Ascorbic Acid-Mediated Cytotoxicity in Prostate Cancer In Vitro | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Environmental Health and Engineering | |
| thesis.degree.discipline | Environmental Health & Engineering | |
| thesis.degree.grantor | Johns Hopkins University | |
| thesis.degree.grantor | Bloomberg School of Public Health | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Sc.M. |