The number of proton therapy facilities and the clinical usage of high energy proton beams for cancer treatment has substantially increased over the last decade. This is mainly due to the superior dose distribution of proton beams resulting in a reduction of side effects and a lower integral dose compared to conventional X-ray radiotherapy. More recently, the usage of metallic nanoparticles as radiosensitizers to enhance radiotherapy is receiving growing attention. While this strategy was originally intended for X-ray radiotherapy, there is currently a small number of experimental studies indicating promising results for proton therapy. However, most of these studies used low proton energies, which are less applicable to clinical practice; and very small gold nanoparticles (AuNPs). Therefore, this proof of principle study evaluates the radiosensitization effect of larger AuNPs in combination with a 200 MeV proton beam. CHO-K1 cells were exposed to a concentration of 10 μg/ml of 50 nm AuNPs for 4 hours before irradiation with a clinical proton beam at NRF iThemba LABS. AuNP internalization was confirmed by inductively coupled mass spectrometry and transmission electron microscopy, showing a random distribution of AuNPs throughout the cytoplasm of the cells and even some close localization to the nuclear membrane. The combined exposure to AuNPs and protons resulted in an increase in cell killing, which was 27.1% at 2 Gy and 43.8% at 6 Gy, compared to proton irradiation alone, illustrating the radiosensitizing potential of AuNPs. Additionally, cells were irradiated at different positions along the proton depth-dose curve to investigate the LET-dependence of AuNP radiosensitization. An increase in cytogenetic damage was observed at all depths for the combined treatment compared to protons alone, but no incremental increase with LET could be determined. In conclusion, this study confirms the potential of 50 nm AuNPs to increase the therapeutic efficacy of proton therapy.
29 January 2019 in BMC Complementary and Alternative Medicine
Colorectal malignant neoplasms is one of the leading causes of death in both men and women in the developed world and the incidence has recently increased markedly in South Africa. Studies have highlighted the beneficial effects of Amygdalin, a cyanogenic compound found in both peach and apricot kernels, in its ability to suppress the development of colon cancer. The focus of this study was to investigate the potential anti-proliferative properties of various apricot and peach kernels extractions from South Africa and China and to monitor alterations in cell cycle kinetics in colon cancer cells. Studies were conducted on HT-29 colon cancer cells. The interactive role of three different kernel extractions on the modulation of cell proliferation, apoptosis and cell cycle progression was monitored over 24, 48 and 72 h periods. After 24 h, all extracts of the South African apricot kernels had a dose related bi-phasic proliferative effect on the HT-29 cells. It stimulated cell proliferation at the lowest and highest concentrations while at 500 μg/mL it inhibited cell proliferation. In contrast, after 72 h, the low concentration inhibited cell proliferation while the 500 μg/mL extracts stimulated cell proliferation. Morphological changes were observed in cells incubated with Chinese kernel extracts after 24 h and South African kernel treatment (1000 μg/mL) after 72 h. A possible intra-S-phase block after 24 and 48 h exposure to South African hydrophilic kernel extracts was observed. This transient block that is more concerned with tolerating and accommodating damage during replication rather than repairing it, could explain the initial anti-proliferative effects observed after 24 h exposure to the various Chinese kernel extract concentrations. Abrogation of the block by exhaustion of the cyanide production, most likely allowed the cells to resume the cell cycle and continue into mitosis, whereas low ATP levels caused by the presence of amygdalin in the kernels, can also cause the induction of pycnosis or necrosis. These results highlight the possible mechanisms of growth inhibition by amygdalin containing extracts and may contribute towards the development of dietary anti-cancer therapies.
The indiscriminate use of non-regulated skin lighteners among African populations has raised health concerns due to the negative effects associated with skin lightener toxicity. For this reason, there is a growing interest in the cosmetic development of plants and their metabolites as alternatives to available chemical-derived skin lightening formulations. Approximately 90% of Africa’s population depends on traditional medicine, and the continent’s biodiversity holds plant material with various biological activities, thus attracting considerable research interest. This study aimed to review existing evidence and document indigenous African plant species capable of inhibiting the enzyme tyrosinase and melanogenesis for potential incorporation into skin lightening products. Literature search on melanin biosynthesis, skin lightening, and tyrosinase inhibitors resulted in the identification of 35 plant species were distributed among 31 genera and 21 families across 15 African countries and 9 South African provinces. All plants identified in this study showed competent tyrosinase and melanogenesis inhibitory capabilities. These results indicate that African plants have the potential to serve as alternatives to current chemically-derived skin lighteners.
Differential anti-proliferative and pro-apoptotic effects of aqueous extracts of green rooibos (Rg;Aspalathus linearis) and green tea (GT;Camellia sinensis) and an aspalathin-enriched extract of green rooibos (GRE), were investigated in primary rat hepatocytes (PH) and human liver (HepG2) and colon (HT-29) cancer cells. Rooibos flavonoids, aspalathin and luteolin, and the green tea flavanol, epigallocatechin gallate (EGCG), were included to assess their contribution relative to their extract concentrations. GRE was the most effective in reducing cell growth parameters which was associated with a high total polyphenol content and high ferric reducing potential. Differential cell responses were noticed with HepG2 cells more sensitive than PH toward the induction of apoptosis by GRE. Luteolin induced apoptosis in PH and HepG2 cells while aspalathin lacked any effect. EGCG induced apoptosis in HepG2 cells while PH were resistant. HT-29 cells were resistant to apoptosis induction by the tea and pure flavonoids. Differences existed in the individual effects of the major rooibos and GT flavonoids against cell growth parameters compared to their equivalent concentrations in the extract mixtures. Diversity of the flavonoid constituents, physicochemical properties and cellular redox status governing cell survival are likely to explain the differential cell responses.
Following population declines of the African savanna elephant (Loxodonta africana) across the African continent, the establishment of primary cell lines of endangered wildlife species is paramount for the preservation of their genetic resources. In addition, it allows molecular and functional studies on the cancer suppression mechanisms of elephants, which have previously been linked to a redundancy of tumor suppressor gene TP53. This methodology describes the establishment of primary elephant dermal fibroblast (EDF) cell lines from skin punch biopsy samples (diameter: ±4 mm) of African savanna elephants (n = 4, 14–35 years). The applied tissue collection technique is minimally invasive and paves the way for future remote biopsy darting. On average, the first explant outgrowth was observed after 15.75 ± 6.30 days. The average doubling time (Td) was 93.02 ± 16.94 h and 52.39 ± 0.46 h at passage 1 and 4, respectively. Metaphase spreads confirmed the diploid number of 56 chromosomes. The successful establishment of EDF cell lines allows for future elephant cell characterization studies and for research on the cancer resistance mechanisms of elephants, which can be harnessed for human cancer prevention and treatment and contributes to the conservation of their genetic material.