Elucidation of Mechanism of Action of Novel Capsazepine Analog, CIDD-000099

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dc.contributor.advisorForsthuber, Thomas G.
dc.contributor.advisorSingh, Brij B.
dc.contributor.authorZboril, Emily Kate
dc.contributor.committeeMemberGonzales, Cara
dc.contributor.committeeMemberRenthal, Robert
dc.creator.orcidhttps://orcid.org/0000-0001-8315-5785
dc.date.accessioned2024-03-08T17:35:11Z
dc.date.available2022-05-27
dc.date.available2024-03-08T17:35:11Z
dc.date.issued2020
dc.descriptionThis item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.
dc.description.abstractOral cancer patients generally have a poor prognosis, with only about 60% of patients surviving 5-years after diagnosis. Treatments for oral cancer have many adverse side effects and further studies must be done to develop drugs that are more efficacious and result in fewer side effects. To achieve this, CIDD-000099 was developed by the laboratory of Dr. Cara Gonzales DDS, PhD at the UT Health Dental School along with the Center for Innovative Drug Discovery at The University of Texas at San Antonio based on the vanilloid molecule, capsazepine. CIDD-000099 has been shown to produce cytotoxic effects in multiple cancer cell lines, including oral squamous cell carcinoma (OSCC). The present study sought to evaluate the nature of that cytotoxicity and further elucidate its mechanism of action. The results show that CIDD-000099 is able to reduce cell viability in OSCC cell lines Cal27 and HSC-3 in both a dose- and time-dependent manner. Furthermore, investigation of Bcl-family proteins and the cleavage of PARP showed that cancer cells treated with this drug undergo apoptosis. We hypothesized that this could be due to either i) inhibition of mitochondrial function, or ii) induction of ER stress. We determined that in cells treated with CIDD-000099, both complex II of electron transport and ATP synthase (complex V), which is involved in oxidative phosphorylation and ATP generation, are inhibited. Moreover, the results also showed an increase in ER stress markers and an inability of treated cells to achieve calcium homeostasis following exhaustion of calcium stores. While we have established that both ER stress and mitochondrial dysfunction are part of the cellular response to CIDD-000099, further studies will need to be done to determine if one initiates or potentiates the other.
dc.description.departmentIntegrative Biology
dc.format.extent40 pages
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12588/6109
dc.languageen
dc.subjectCalcium Signaling
dc.subjectMytochondrial Dysfunction
dc.subjectNovel Drug
dc.subjectOral Cancer
dc.subjectOral Squamous Cell Carcinoma
dc.subject.classificationBiology
dc.titleElucidation of Mechanism of Action of Novel Capsazepine Analog, CIDD-000099
dc.typeThesis
dc.type.dcmiText
dcterms.accessRightspq_closed
thesis.degree.departmentIntegrative Biology
thesis.degree.grantorUniversity of Texas at San Antonio
thesis.degree.levelMasters
thesis.degree.nameMaster of Science

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