Abstract
BackgroundCancer as a multistage process can be reversed or blocked by using chemopreventive agents. Colon cancer chemoprevention has been widely investigated using cyclooxygenase inhibitors and many other chemicals of synthetic or natural origin. This particular study was carried out to assess the colon cancer chemopreventive effect of hydro-methanol extract of Rumex abyssinicus rhizome on rats.MethodColon cancer chemopreventive potential of hydro-methanol extract of Rumex abyssinicus rhizome was determined based on the number and multiplicity of aberrant crypt foci (ACF). Fifteen DMH (1, 2-dimethylhydrazine) treated and five untreated Wistar female rats were used. DMH was administered subcutaneously 30 mg/kg, after its pH was adjusted to 6.5–7. Treatment groups started receiving extract after six weeks of weekly DMH injections. The rats were divided in to four groups: Group 1 received only oral normal saline, Group 2 received DMH and normal saline, Group 3 and 4 received DMH plus 250 mg/kg and 500 mg/kg extract, respectively. Specific phytoconstituents of the plant, which were reviewed from original articles, were virtually evaluated for cyclooxygenase-2 (COX-2) inhibition. The binding energies and interactions of the phytochemicals from Rumex abyssinicus against COX-2 were determined by Autodock4.2.ResultsThere was a statistically significant reduction (p-value < 0.05) in the number of aberrant crypt (AC) and aberrant crypt foci (ACF) at both administered doses. However, significant association (p-value > 0.05) was not observed in reducing crypt multiplicity. The docking process resulted in estimated binding energies [−6.83 kcal/mol to −7.9 kcal/mol] which are closer to the positive controls or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) [−4.55 kcal/mol to −10.84 kcal/mol]. The phytochemical-COX-2 interaction indicated the involvement of key amino acid residues in inhibition of cyclooxygenase like ARG120, TYR355, TYR385, SER530 and GLY526.ConclusionsRumex abyssinicus had demonstrated a chemopreventive potential at post-initiation stage. As the virtual screening data suggested, COX-2 inhibition by the anthraquinones in the extract could be one mechanism for the observed chemopreventive effect.
Highlights
Cancer as a multistage process can be reversed or blocked by using chemopreventive agents
The docking process resulted in estimated binding energies [−6.83 kcal/mol to −7.9 kcal/mol] which are closer to the positive controls or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) [−4.55 kcal/mol to −10.84 kcal/mol]
The phytochemical-COX-2 interaction indicated the involvement of key amino acid residues in inhibition of cyclooxygenase like ARG120, TYR355, TYR385, SER530 and GLY526
Summary
Cancer as a multistage process can be reversed or blocked by using chemopreventive agents. Colon cancer chemoprevention has been widely investigated using cyclooxygenase inhibitors and many other chemicals of synthetic or natural origin. Curative and palliative therapies of colon cancer have commonly relied on surgery, chemotherapy and radiotherapy [2] Apart from these major strategies, a relatively recent fourth method, which is called chemoprevention, is being pursued. It is the use of natural or synthetic compounds to block, reverse, or prevent the development of invasive cancers [3]. NonSteroidal Anti-Inflammatory Drugs (NSAIDs) has been widely studied for chemoprevention of colon cancer Despite their effectiveness, gastrointestinal perforation due to non-selective inhibition of cyclooxygenase enzymes has limited their use [4]. In eight weeks post-initiation animal study, red ginseng significantly reduced the incidence of ACF, which indicates potential for colon cancer chemoprevention [6]
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