Synergistic effect of novel aspirin analogues in a colorectal cancer cell line

Abstract

Studies show aspirin, a non-steroidal anti-inflammatory drug (NSAID) has potential to decrease incidence of, or mortality from a number of cancers including colorectal cancer (CRC). With emphasis on the treatment of CRC involving platinum compounds, oxaliplatin has been used in several combinations with other drugs. Unfortunately, these combinations do not improve overall survival and are accompanied with side effects that include gastrointestinal (GI), hematologic, neurologic toxicities, myopathy, and most recently interstitial lung disease, particularly fibrotic hypersensitivity pneumonitis, which has high mortality rates and long-term morbidity in survivors. The need of compounds that will reduce the doses of platinum compounds required for chemotherapy in order to reduce or alleviate these side effects is long overdue. This study investigates the synergistic effect if any, of novel aspirin analogues with platinum compounds cisplatin, oxaliplatin and carboplatin in order to lower doses needed of these platinum compounds and thus reduce or alleviate common debilitating side effects. MTT assay was used to assess cell viability and the CompuSyn software (Paramus, NJ, 2005) was used to calculate CI and DRI at ED₅₀, ED₇₅ and ED₉₀. Oxaliplatin was found to exhibit synergistic effects when combined with p-aspirin (PN549), diaspirin (PN508) and o-thioaspirin (PN590). Although further investigations such as in vivo experiments will be needed to draw any conclusions, this study is a stepping-stone for platinum compounds and aspirin drug combinations in order to decrease doses needed for treatment and thus lessen or alleviate debilitating side effects.

Keywords: Colorectal cancer; Aspirin; Aspirin analogues; Oxaliplatin; DMSO