Mechanism of Action of Flavonoids in Prevention of Inflammation- Associated Skin Cancer.

Skin cancer in humans represents about 30% of all new cancers and is by far the most common malignancy in the Caucasian population. Exposure to radiations especially ultraviolet-B (UV-B) radiation is the major cause for development of skin cancers along with other chemical or biological factors. The growing incidence rates of skin cancer around the world, demand the need for new treatment options. Understanding the etiology and pathogenesis of skin cancer is therefore crucial for developing an effective drug against this prevailing disease. Medicinal plants are rich with numerous secondary metabolites such as flavonoids, which are now known to treat various chronic diseases, including inflammations and cancers. Flavonoids are sub-classified in to flavones, flavonols, iosflavones, flavanones, flavanols and anthocyanidins. They act on different targets including scavenging reactive oxygen species (ROS), regulation of the cell cycle, and initiation of DNA repair mechanisms, apoptotic induction and inhibition of metastasis. Innumerable evidence suggested that an increased consumption of flavonoid-rich fruits and vegetables rendered DNA protection to normal skin exposed to carcinogens such as UV-B radiation. Flavonoids also showed the potential to induce cell death mechanisms in melanoma, the most dreadful form of skin cancer. This comprehensive review presents flavonoids and their mechanism of action in relation to inflammation and skin cancer management.

Class II Analphoid Chromosome in a Child with Aberrant Chromosome 7: A Rare Cytogenetic Association.

A neocentromere is a functional centromere that has arisen within a region not known to have a centromere. We present a case with a very rarely reported class II neocentromere formation in an aberrant chromosome 7. A 22-month-old male was referred because of dysmorphic features. Banding cytogenetics was performed, and a ring 7 and a supernumerary marker chromosome along with a normal chromosome 7 were found. In situ hybridization using a centromeric probe revealed 46 signals, of which 2 signals for chromosome 7 were observed, one on the normal and one on the ring chromosome. Further analysis using FISH revealed that the linear acentric fragment was part of the 7q region, which suggests that there could be a possible McClintock mechanism.

In Vitro Protective Potentials of Annona muricata Leaf Extracts Against Sodium Arsenite-induced Toxicity.

Sodium arsenite (NaAsO2) is a metalloid which is present widely in the environment and its chronic exposure can contribute to the induction of oxidative stress, resulting in disturbances in various metabolic functions including liver cell death. Hence, there is a need to develop drugs from natural sources, which can reduce arsenic toxicity. While there have been reports regarding the antioxidant and protective potentials of Annona muricataleaf extracts, our study is the first ofits kind to extend these findings by specifically evaluating its ability to render protection against sodium arsenite (NaAsO2) induced toxicity (10 µM) in WRL-68 (human hepatic cells) and human erythrocytes by employing XTT and haemolysis inhibition assays respectively. The methanolic extract exhibited higher activity than the aqueous extract in both assays. The results showed a dose-dependent decrease in arsenic toxicity in both WRL-68 cells and erythrocytes, suggesting the protective nature of Annona muricatato mitigate arsenic toxicity. Hence the bioactive extracts can further be scrutinized for the identification and characterization of their principal contributors.

Cancer-specific chemoprevention and anti-metastatic potentials of Rheum emodi rhizome ethyl acetate extracts and identification of active principles through HPLC and GC-MS analysis.

Rheum emodi Wall. ex Meissn. (Polygonaceae) is a Himalayan perennial herb which has been cultivated over 5000 years for its medicinal properties by rural and tribal people of Kashmir, and has great significance for its traditional use in Ayurvedic, Unani and folk systems of medicine for cancer treatments. However, there is lack of reports pertaining to specific-chemopreventive properties of R. emodi rhizome. The present study investigates R. emodi rhizome hot and cold ethyl acetate extracts (EHR and ECR) for specific-chemopreventive properties. The extracts were found to be effective antioxidant sources, and showed significant (P<0.05) cancer-specific cytotoxicity towards MDA-MB-231 cells (when compared to WRL-68 [non-tumoral cells]) with IC(50) values of 56.59±1.29 µg/ml (EHR) and 152.38±1.45 µg/ml (ECR) respectively, and induced apoptosis significantly (P<0.05) high in MDA-MB-231 cells (estrogen receptor-(ER)-negative) when compared to MCF-7 cells (ER-positive). Extracts also demonstrated evident anti-metastatic activity. Further, the extracts were chemically characterized through HPLC analysis which revealed major polyphenolics and the GC-MS analysis of the effective extract EHR unveiled (Methyl 6,7-dideoxy-6-C-methyl-2,3-di-O-methyl-à-D-gluco-oct-6-eno-1,5-pyranosid)urono-8,4-lactone,Chrysophanol, derivatives of cyclopropanes and a quinazoline derivative. Overall, EHR exhibited significantly better results on par with ECR, and thus could be considered for their use in designing cancer-specific chemopreventive agents against ER-negative breast cancer.

Comparative studies to evaluate relative in vitro potency of luteolin in inducing cell cycle arrest and apoptosis in HaCaT and A375 cells.

Luteolin is a naturally occurring flavonoid present in many plants with diverse applications in pharmacology. Despite several studies elucidating its significant anti-cancer activity against various cancer cells, the mechanism of action in skin cancer is not well addressed. Hence, we investigated the effects of luteolin in HaCaT (human immortalized keratinocytes) and A375 (human melanoma) cells. The radical scavenging abilities of luteolin were determined spectrophotometrically, prior to a cytotoxic study (XTT assay). Inhibitory effects were assessed by colony formation assay. Further, the capability of luteolin to induce cell cycle arrest and apoptosis were demonstrated by flow cytometry and cellular DNA fragmentation ELISA, respectively. The results revealed that luteolin possesses considerable cytotoxicity against both HaCaT and A375 cells with IC50 values of 37.1 µM and 115.1 µM, respectively. Luteolin also inhibited colony formation and induced apoptosis in a dose and time-dependent manner by disturbing cellular integrity as evident from morphological evaluation by Wright- Giemsa staining. Accumulation of cells in G2/M (0.83-8.14%) phase for HaCaT cells and G0/G1 (60.4-72.6%) phase for A375 cells after 24 h treatment indicated cell cycle arresting potential of this flavonoid. These data suggest that luteolin inhibits cell proliferation and promotes cell cycle arrest and apoptosis in skin cancer cells with possible involvement of programmed cell death, providing a substantial basis for it to be developed into a potent chemopreventive template for skin cancer.