Cisplatin is an anti-cancer drug effective against several cancers which can produce the serious side-effect of hearing loss. Curcumin, a natural plant compound, can increase the activity of cisplatin against cancer and counteract cisplatin’s effect against hearing. Because curcumin exhibits poor bioavailability, there is considerable interest in developing synthetic curcumin analogs (curcuminoids) that are more soluble and which retain anti-cancer activity and otoprotective function. This study investigated whether two curcuminoids, EF-24 and CLEFMA, increase the cytotoxic and ototoxic effects of cisplatin against the lung cancer cell line, A549, and the colorectal cancer cell line, Caco2. Cytotoxicity was measured by using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Ototoxicity was quantified by measuring hearing thresholds acquired by the auditory evoked potential technique in a zebrafish (Danio rerio) model. The results of this study indicate that a combination of cisplatin with either CLEFMA or EF-24, produces a dose-dependent effect against the cancer cell-lines which is not synergistic or additive. The hearing tests showed that both curcuminoids could prevent hearing loss caused by cisplatin treatment. However, the curcuminoid vehicle, DMSO, could also play a role in the effect on hearing. These results suggest that curcuminoid treatment may increase the effect of cisplatin against these cancers and might also reduce hearing damage produced by cisplatin treatment. Future research is needed to investigate the signaling pathways that regulate the function of cisplatin, CLEFMA, EF-24 and DMSO in cancer and auditory physiology.
Advisor(s) or Committee Chair
Dr. Michael Smith
Biochemistry | Cancer Biology | Neuroscience and Neurobiology | Oncology
Hodzic, Denis, "Investigating the Synergistic Effects of Cisplatin and Two Curcuminoid Compounds on Cancer" (2017). Honors College Capstone Experience/Thesis Projects. Paper 687.