Hypericum alpestre extract exhibits in vitro and in vivo anticancer
properties by regulating the cellular antioxidant system and metabolic
pathway of L-arginine
Abstract
Conventional treatment methods are not effective enough to fight the
rapid increase in cancer cases. The interest is increasing in the
investigation of herbal sources for the development of new anticancer
therapeutics. Particularly, much attention is given to finding combined
phytochemical/chemotherapeutic treatment models to overcome drug
resistance and decrease side effects. The aim was to investigate the
antitumor capacity of Hypericum alpestre herb extract in
vitro and in vivo, either alone or combined with the inhibitors
of the L-arginine/polyamine/nitric oxide pathway and characterize its
active phytochemicals using advanced chromatographic techniques. The
antioxidant capacity of H. alpestre extract was assessed through
chemical spectrophotometric tests (DPPH and ABTS) and in biological
systems using Cellular Antioxidant Activity assay. The inhibitory effect
of H. alpestre extract on the growth of human colorectal (HT29)
and breast cancer (MCF-7) cell cultures was explored by the MTT test.
The genotoxicity of the tested extract was studied using a comet assay.
In vivo, the antitumor properties of H. alpestre and its
combinations were explored in a rat mammary gland carcinogenesis model
induced by subcutaneous injection of 7,12-dimethylbenz[a]anthracene.
The polyphenolic substances present in H. alpestre extract have
been characterized using the LC-Q-Orbitrap HRMS system. The H.
alpestre extract expressed promising antiproliferative effects on MCF-7
and HT29 cells. The extract did not exhibit genotoxic activity nor
possessed antigenotoxic properties. The in vivo rat mammary
carcinogenesis model data showed that the H. alpestre extract
stimulated the activity of antioxidant enzymes in the liver, brain, and
tumors of rats in the experimental groups, demonstrating its antioxidant
protective effects. The herb alone and in combination with N
ω-OH-nor-L-arginine and N
ω-nitro-L-arginine methyl ester exhibited
pro-/antioxidant, antiproliferative, anti-angiogenic, and cytotoxic
effects.