Abstract

Our
previous studies on three plants - Garcinia
kola (GK), Uvaria Chamae (UC) and
Olax subscorpioidea (OS) - provided
evidence for the chemopreventive and chemotherapeutic potential of their
extracts. Therefore, to elucidate the associated mechanisms, in this study, using
appropriate in vitro models we
investigated the effects of these plants on cell viability and on molecular pathways
linked to carcinogenesis or cancer progression, including inflammation and
oxidative stress. We investigated the toxicity of the extracts to the HeLa,
AREc32 (MCF-7), PC3 and A549 cell lines. We also explored their potential to
inhibit lipopolysaccharide (LPS)-induced Nitric Oxide (NO) production in RAW 264.7 cells (murine macrophages), their ability to
induce cellular reactive oxygen species (ROS) or modulate against hydrogen
peroxide-induced elevation of ROS in HeLa cells, and their effect on Nrf2/ARE
activation. We then attempted some phytochemical investigation of the
constituent principles in the extracts that might underlie the observed effects.
Effects of extracts on cytotoxicity were assessed using the absorbance-based
MTT assay and the fluorescence-based alamar blue (AB) assay. Nitric oxide
production was assessed using the Griess Reagent System, cellular ROS changes
were assessed using the DCFDA (2', 7'-dichlorofluorescein diacetate) Assay and effects
on the Nrf-2/ARE pathway were assessed through the luciferase reporter assay in
the stable human mammary MCF-7-derived reporter cell line (the AREc32 cell line).
Extracts of OS and GK elicited significant toxicity to HeLa (IC₅₀:
73.15 µg/ml, 49.95 µg/ml, respectively), AREc32 (IC₅₀ 39.71 µg/ml,
58.03 µg/ml, respectively) and A549 (IC₅₀: 26.33 µg/ml, 10.91 µg/ml,
respectively) cells. OS
and UC extracts were significant inhibitors of NO release following LPS stimulation
of murine macrophages, while the three extracts significantly inhibited NO
release following potentiation of the action of LPS with Interferon-γ (IFN-γ). The three extracts also significantly reduced
basal and peroxide-induced ROS in HeLa cells in the DCFDA assay. UC was a
potent activator of Nrf2/ARE in the luciferase reporter assay. Ion spectra data (m/z; MS) revealed the possible
presence of Chamanetin, Isochamanetin, Isouvaretin, Uvaricin I and some other
constituents in U. chamae root extract
and of the flavonoids Kolaviron, Garcinia Biflavones 1, 1a and 2 in G.
kola stem bark extract. With anti-inflammatory, antioxidant and
cytotoxic activities being closely linked with the potential for use in the chemoprevention
and chemotherapy of cancers, the roles of these plant extracts in traditional anticancer
remedies are hereby further highlighted, as well as the plants’ potential to be
sources of novel anti-cancer compounds