Cancer has long been a grievous disease complicated by innumerable players aggravating its cure. Many clinical studies demonstrated the prognostic relevance of the tumor suppressor protein p53 for many human tumor types. Overexpression of mutated p53 with reduced or abolished function is often connected to resistance to standard medications, including cisplatin, alkylating agents (temozolomide), anthracyclines, (doxorubicin), antimetabolites (gemcitabine), antiestrogenes (tamoxifen) and EGFR-inhibitors (cetuximab). Such mutations in the TP53 gene are often accompanied by changes in the conformation of the p53 protein. Small molecules that restore the wild-type conformation of p53 and, consequently, rebuild its proper function have been identified. These promising agents include PRIMA-1, MIRA-1, and several derivatives of the thiosemicarbazone family. In addition to mutations in p53 itself, p53 activity may be also be impaired due to alterations in p53s regulating proteins such as MDM2. MDM2 functions as primary cellular p53 inhibitor and deregulation of the MDM2/p53-balance has serious consequences. MDM2 alterations often result in its overexpression and therefore promote inhibition of p53 activity. To deal with this problem, a judicious approach is to employ MDM2 inhibitors. Several promising MDM2 inhibitors have been described such as nutlins, benzodiazepinediones or spiro-oxindoles as well as novel compound classes such as xanthone derivatives and trisubstituted aminothiophenes. Furthermore, even naturally derived inhibitor compounds such as a-mangostin, gambogic acid and siladenoserinols have been discovered. In this review, we discuss in detail such small molecules that play a pertinent role in affecting the p53-MDM2 signaling axis and analyze their potential as cancer chemotherapeutics.

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In the paradigm of drug administration, determining the correct dosage of a therapeutic is often a challenge. Several drugs have been noted to demonstrate contradictory effects per se at high and low doses. This duality in function of a drug at different concentrations is known as hormesis. Therefore, it becomes necessary to study these biphasic functions in order to understand the mechanistic basis of their effects. In this article, we focus on different molecules and pathways associated with diseases that possess a duality in their function and thus prove to be the seat of hormesis. In particular, we have highlighted the pathways and factors involved in the progression of cancer and how the biphasic behavior of the molecules involved can alter the manifestations of cancer. Because of the pragmatic role that it exhibits, the imminent need is to draw attention to the concept of hormesis. Herein, we also discuss different stressors that trigger hormesis and how stress-mediated responses increase the overall adaptive response of an individual to stress stimulus. We talk about common pathways through which cancer progresses (such as nuclear factor erythroid 2-related factor 2-Kelch-like ECH-associated protein 1 (Nrf2-Keap1), sirtuin-forkhead box O (SIRT-FOXO) and others), analyzing how diverse molecules associated with these pathways conform to hormesis.

We suggest certain perspectives, by which we as scientists, may contribute towards prevention of biopiracy and also to foster the fair utilization of natural resources. We discuss ways, in which the interests of indigenous people especially from developing countries can be secured.

Cancer is a leading cause of mortality and the annual incidence of new cancer cases is rising worldwide. Due to the frequent development of resistance and the side effects of established anti-cancer drugs, the quest for new drugs with improved therapeutic features goes on. In contrast to cytotoxic chemotherapy of the past, the concept of targeted chemotherapy attempts to increase specificity of therapy by attacking tumor-related mechanisms. A novel emerging treatment concept represents the inhibition of centrosomal clustering. The centrosome regulates mitotic spindle formation assuring uniform separation of chromosomes to daughter cells. Many tumors contain supernumerary centrosomes, which contribute to aneuploidy induction via multipolar mitotic spindle formation. As spindle multipolarity leads to cell death, tumor cells developed centrosomal clustering mechanism to prevent multipolar spindle formation by coalescence of multiple centrosomes into two functional spindle poles. Inhibition of centrosome clustering represents a novel strategy for drug development and leads to the formation of multipolar spindles and subsequent cell death. In the present review, we report advances in understanding the biology of centrosomal clustering as well as enlist compounds capable of inducing the formation of multipolar spindles such as indolquinolizines, integrin-linked kinase inhibitors (QLT-0267), noscapinoids (EM011), phthalamide derivatives (TC11), griseofulvin, phenanthridines (PJ-34), CCC1-01, CW069 GF-15, colcemid, nocodazole, paclitaxel, and vinblastine. We also present in silico result of compounds that bind to γ-tubulin under the ambit of centrosomal clustering inhibition. We observed maximum binding efficacy in GF-15, CW069, paclitaxel and larotaxel with GF-15 exhibiting least energy of -8.4 Kcal/mol and 0.7 μM Pki value.