Sustained use of antimutagenic bioactives having affinity with DNA minor groove could prevent in vitro neoplastic induction

Abstract

Introduction

Studies on the antimutagenic and anti-neoplastic effect of dietary ingredients can be useful in developing nutraceuticals for preventing neoplastic induction. In the current study the query whether food rich in antimutagenic potential equally suppress the neoplastic induction, was addressed, with potential mechanism of action.

Methods

The antimutagenic activity was evaluated using the TK6 gene mutation assay, assessing the reduction in ethyl methanesulfonate (EMS)-induced mutation in presence of vegetable extracts. The anti-⁠neoplastic activity was assessed using the C3H/⁠10T1/⁠2 cell transformation assay, quantifying the inhibition of anchorage-independent growth and type III foci formation. The prominent compounds in the vegetable extract were characterised using gas chromatography-⁠mass spectrometry (GC-⁠MS), and their interactions with DNA were predicted using molecular docking.

Results

Among the vegetable extracts, garlic exhibited the most potent antimutagenic and anti-neoplastic effects, followed by spinach and beans. Garlic extract exhibited significantly high antimutagenic potential (59 ± 3%), and anti-neoplastic activity in the terms of inhibition of anchorage independence (65 ± 3%) and inhibition of type III foci formation (90 ± 5%). GC-MS analysis of garlic extract identified abundant organosulphur compounds, terpenes, and terpenoids. Molecular docking studies suggested that these compounds bind to the DNA minor groove with binding energies ranging from −⁠4.3 to −⁠7.21 kcal mol^-⁠1.

Discussion

The antimutagenic and antineoplastic activities showed a positive correlation (r = 0.92–0.93), where garlic extract showed the highest potential. The DNA binding properties of the prominent compounds in garlic extract suggests a potential mechanism of action involving interference with carcinogen activity and subsequent prevention of gene dysregulation.