Identification of Biomarkers Associated with Cancer Using Integrated Bioinformatic Analysis

Among the leading cause of death cancer ranked in top position. Early diagnosis of cancer holds promise for reduced mortality rate and speedy recovery. The cancer associated molecules being altered in terms of under/over expression when compared to normal cells and thus could act as biomarkers for therapeutic designing and drug repurposing. The information about the known cancer associated biomarkers can be exploited for targeting of cancer specifically in terms of selective personalized medicine designing. This chapter deals with various types of biomarkers associated with different types of cancer and their identification using integrated bioinformatic analysis. Besides, a brief insight on integrated bioinformatics analysis tools and databases have also been discussed

Conjugation of chlorin p<SUB>6</SUB> to histamine enhances its cellular uptake and phototoxicity in oral cancer cells

Purpose Our previous studies in hamster cheek pouch model have shown that chlorin p<SUB>6</SUB> (Cp<SUB>6</SUB>), a chlorophyll derivative is a suitable photosensitizer for photodynamic treatment (PDT) of small tumors (&lt;5 mm). However, for bigger tumors, the accumulation of Cp<SUB>6</SUB> was inadequate, which compromised the effectiveness of PDT. The purpose of present study was to investigate the possibility of improving the cellular uptake of Cp<SUB>6</SUB> by conjugating it to histamine, a biogenic amine that is known to modulate tumor growth and development via cell surface receptors. Methods The conjugate of Cp<SUB>6</SUB> and histamine (Cp<SUB>6</SUB>-his) was prepared by carbodiimide coupling reaction. Cellular uptake, intracellular localization and cytotoxicity of both Cp<SUB>6</SUB> and its conjugate were investigated in two human oral cancer cell lines (4451 and NT8e). The percentage of necrotic and apoptotic cells after PDT were also estimated using Hoechst 33342-propidium iodide staining. Results In both the cell line, the cellular uptake of Cp<SUB>6</SUB>-his was found to be ~10 times higher when compared to Cp<SUB>6</SUB>. Histamine led to a slight increase in intracellular uptake of Cp<SUB>6</SUB>-his, whereas ranitidine, a histamine H2 receptor antagonist, and incubation at lower temperature (~15°C) led to its inhibition, suggesting that uptake of Cp<SUB>6</SUB>-his is receptor mediated. Results on western blot confirmed the presence of H2 receptor in both the cell line. Observations on intracellular localization revealed that unlike Cp<SUB>6</SUB>, which localized on multiple sites, Cp<SUB>6</SUB>-his showed localization on the cell membrane and around the perinuclear region. Moreover, the phototoxicity induced by Cp<SUB>6</SUB>-his was ~4 times higher when compared to Cp<SUB>6</SUB> in both the cell lines. There was, however, no significant difference in the mode of cell death. Conclusion Results suggest that conjugating Cp<SUB>6</SUB> with histamine can help improve the effectiveness of PDT in oral cancer cells by enhancing its intracellular delivery

Phytochemicals based therapeutic approaches for Breast cancer targeting: Molecular docking study

Abstract Background: Cancer is a prominent cause of disease burden all over the world. Primary cause of the development of cancer is exposure to potentially hazardous environmental factors and unhealthy lifestyle. Among all types of cancer, breast cancer is most common in women and becomes a public health issue on a global scale. There has been considerable interest in the development of drugs which can target cancer-causing hotspot factors such as mTOR, estrogen receptor alpha, and progesterone receptor to cure breast cancer. The key focus of the present work is to search plant-based phytochemical molecules which can efficiently interact with the targeted proteins responsible for the development and progression of breast cancer using molecular docking studies. Methods: We have screened 1064 phytochemical molecules from plant sources against 5 potential hotspot targets: EGFR kinase domain, Human estrogen receptor alpha ligand-binding domain, FRB fragment of mTOR, Progesterone receptor, and NUDT5 of breast cancer. Results: Our results show that among all molecules, 25 phytochemicals exhibit promising therapeutic potential for breast cancer treatment. Our observation is further strengthened by the available literatures showing the promising therapeutic efficacy exhibited by these lead molecules in in vitro and in vivo cancer models. Conclusion: The virtual screening of phytochemicals hold promise to search potential anticancer drug. Among the lead molecules, Delphinidin 3,5-diglucoside, Baicalein, and Morphine have already been known for their anticancer properties, but the efficacy of Vitexin, IsoSkimmiwallin, Nodifloretin, Jaceosidin and Nepetin have not been explored so far and therefore further in-vitro and in-vivo study is warrante