Hormetic effect of an Ethanolic Graviola Leaf Extract on HGF-1 cells survival.

Plant-extracted compounds have been used for centuries in traditional pharmacopeia. Some of them have proven to be excellent drug alternatives for cancer treatment as they target metabolic pathways that are key to cancer cells such as apoptosis, energy-producing catabolic pathways, and the response to oxidative stress. Since some anticancer drugs have been shown to produce dose dependent biologically opposite effects, it is crucial to determine the range of doses for which the compounds have maximum therapeutic benefits. Annona muricata or Graviola is a tropical tree that is common in the Puerto Rican landscape. Although a plethora of studies conducted in vitro and in vivo studies have indeed reported that extracts prepared from the Graviola root, fruit, bark, and leaves possess antiproliferative activities in a large variety of cancer cells, the efficiency of Graviola extracts to curb the progression of head and neck cancers has been overlooked. Furthermore, the bioactivity of Graviola extracts on sane/non-cancerous cells has largely been ignored. The present work reports the in vitro antiproliferative/anticancer behavior of an ethanolic Graviola leaf extract on squamous cell carcinoma cell lines 9 and 25 vs. a sane/non-cancerous human gingival fibroblast cell line-1. Our results show that the Graviola extract induces cell death in the squamous cell carcinoma cell lines at all concentrations tested and a dose-dependent biphasic concentration-dependent/hormetic effect on the fibroblastic cells. This suggests that, at low doses, the phytochemicals present in the prepared Graviola extract could offer potential therapeutic avenues for curbing the progression of head and neck cancers.

ANTIPROLIFERATIVE PROPERTIES OF ETHANOLIC AND AQUEOUS GRAVIOLA LEAF EXTRACTS ON TONGUE SQUAMOUS CELL CARCINOMA CELL LINE-25.

BACKGROUND: Annona muricata, commonly known as Graviola, soursop or guanabana, is an evergreen tree native to the tropics with a long history of use in ethnomedicine in indigenous communities in Africa and South America. Its active phytoconstituents have provided medicinal benefits against various ailments and diseases such as arthritis, parasitic infection, hypertension, fever, or diabetes. Studies conducted in vitro and in vivo have concluded that Graviola phytocomponents have anti-cancer and anti-tumor properties. One of the characteristics of cancer cells is their uncontrolled proliferation rate. In that sense, molecules that inhibit cell proliferation offer potential therapeutical benefits. METHODS: We prepared ethanolic and aqueous extracts from dried Graviola leaves and tested their respective antiproliferative activities on tongue Squamous Cell Carcinoma cell line-25. We treated the cells with increasing concentrations of the extracts for 24 h. The respective doses leading to a 50% inhibition of cells growth (GI50) were determined. RESULTS: Our results showed that the ethanolic extract was 4 times more active in inhibiting the growth of Squamous Cell Carcinoma cell line-25 than the aqueous extract (respective GI50 of 61.7 µg/mL, and 274.6 µg/mL). CONCLUSION: We hypothesize that some organic compounds involved in the antiproliferative/cytotoxicity of Graviola leaves were selectively extracted by Ethanol. Future plans include characterizing those bioactive compounds and assessing their activity on Squamous Cell Carcinoma cell line-25 vs. non-cancerous oral cells. Our hope is to discover natural molecules to be used as alternative treatments for oral Squamous Cell Carcinomas.

The XRCC1 codon 399 Gln allele is associated with adenine to guanine p53 mutations in non-small cell lung cancer.

The X-ray repair cross-complementing group 1 (XRCC1) gene plays a critical role in the repair of DNA single-strand breaks. A polymorphism at codon 399 of the XRCC1 gene (Arg to Gln) is associated with increased DNA adduct binding and an increase in sister chromatid exchanges after exposure to tobacco carcinogens and may be linked with an increased risk of lung cancer. To further define the interaction between tobacco carcinogens, XRCC1-mediated DNA repair and DNA damage, we examined the role of the XRCC1 codon 399 polymorphism in mutation of the p53 gene in non-small cell lung cancer (NSCLC). Tumor and non-neoplastic (lung or lymphocyte) samples were collected from 116 cigarette smokers with NSCLC. p53 mutations were detected by direct sequencing and/or the GeneChip p53 assay in 63 of 116 (54%) tumors. XRCC1 polymorphisms were identified by PCR/RFLP analysis. The distribution of XRCC1 codon 399 genotypes was (Arg/Arg [74 of 116, 64%], Arg/Gln [29 of 116, 25%], and Gln/Gln [13 of 116, 11%]). The prevalence of p53 mutations was similar among subjects with all three XRCC1 genotypes (Arg/Arg [39 of 74, 53%], Arg/Gln [18 of 29, 62%], and Gln/Gln [6 of 13, 46%]). However, the prevalence of specific p53 mutations varied among different XRCC1 genotypes. AT to GC transitions were significantly (P=0.01) more common among subjects with the Gln/Arg or Gln/Gln genotype (5 of 42, 12%) than in subjects with the Arg/Arg genotype (1 of 74, 1.4%). In summary, the XRCC1 Gln allele is associated with AT to GC mutations in p53 in NSCLC. The XRCC1 gene may play a role in the repair of cigarette smoking-induced DNA damage.