Assessment of Griseofulvin as an Antioxidative Agent and as a Cytotoxic Agent Against Non-Small Cell Lung Adenocarcinoma (A549)

Abstract

Griseofulvin is an antifungal drug used to treat skin infections such as jock itch, athlete's foot, and ringworm. Studies showed that griseofulvin inhibits the proliferation of human cervical carcinoma (Hela) cancer cell by suppressing the spindle microtubule dynamics similar to that of other powerful anti-mitotic drug like taxene (Panda et al., 2005). Since lung cancer is the leading cancer type in the Philippines (Ngelangel and Wang, 2001), this study aimed to assess the chemopreventive properties of griseofulvin and its chemotherapeutic effects against the nonsmall cell lung adenocarcinoma (A549). Using l,l-diphenyl-2-hydrazyl (DPPH) assay to detect free radical scavenging in the compound, griseofulvin had shown no significant antioxidative properties compared to gallic acid, a known antioxidative agent. The methyl thiol tetrazolium (MTT) assay was used to determine the cytotoxicity of the obtained crude griseofulvin preparation. MTT assay revealed that griseofulvin was cytotoxic at an IC50 of 23 pg/ml. This indicated the absence of functional mitochondria which is the initial step to cell death. Morphological studies of the griseofulvin treated cells including presence of membrane blebs, nuclear condensation, and apoptotic bodies, provided insights on the symptoms of a possible apoptotic mode of cell death. At six hours post-treatment, the cell death index of A549 treated with 23 pg/ml griseofulvin increased significantly by 12.3%. Based on the findings of this study, griseofulvin is an effective chemotherapeutic agent but is not chemopreventive. Lastly, being an antifungal agent, griseofulvin lacks significant toxicity to humans (IARC, 1976); in addition, as presented by other anticancer studies, griseofulvin shown no harm in normal cells under specific experimental conditions. These data and supporting information present the potential of griseofulvin in the development of cheaper cancer medicine, and possibly, as an adjuvant to more powerful anticancer drugs.