Current Topics in Medicinal Chemistry - Volume 20, Issue 22, 2020

In the recent past, next-generation sequencing (NGS) approaches have heralded the omics era. With NGS data burgeoning, there arose a need to disseminate the omic data better. Proteogenomics has been vividly used for characterising the functions of candidate genes and is applied in ascertaining various diseased phenotypes, including cancers. However, not much is known about the role and application of proteogenomics, especially Prostate Cancer (PCa). In this review, we outline the need for proteogenomic approaches, their applications and their role in PCa.

Aims: The aim of this study is to explore essential oil from the bark of Cedrus deodara (CDEO) as an potential anticancer agent. Background: The frontline drugs against cancer in clinical settings are posing challenges of resistance and other detrimental side-effects. This has led to the exploration of new anticancer chemical entities from natural sources, particularly plant-based products such as essential oils that serve as vast repositories of pharmacologically active substances for combating cancer. Objective: The objective is to isolate and characterize the essential oil from the bark of Cedrus deodara (CDEO) and evaluate its potential as an anticancer agent and delineate the possible underlying mechanism of action. Methods: Cedrus deodara essential oil from bark (CDEO) was obtained by hydro-distillation and analyzed by GC/MS for vital constituents. Further, in vitro cytotoxic potential was measured by MTT assay against a panel of cancer cell lines. The apoptosis-inducing potential of CDEO was analyzed by mitochondrial membrane potential loss (ΔΨm) and nuclear fragmentation assay. Besides, wound healing assay and colonogenic assay were employed to check the anti-metastatic potential of CDEO. Molecular docking approaches were employed for target identification, while immuno-blotting was carried out for target validation. Results and Discussion: The major components identified were 2-(tert-Buyl)-6-methyl-3-(2- (trifluoromethyl) benzyl)imidazo [1,2-a]pyridine (26.32 %);9- Octadecenoic acid (8.015 %); Copaene (5.181 %);2-(4-Methoxy-2,6-dimethylphenyl) -3-methyl-2H- benzo[g]indazole(4.36 %) and 9(E),11(E)- Conjugated linoleic acid (4.299 %). Further, potent in vitro cytotoxic activity with IC50 values of 11.88 μg/ ml and 14.63 μg/ ml in colon cancer cell lines of HCT-116 and SW-620, respectively. Further, a significant and dose-dependent decrease in colony formation, cell migration, induction of ROS formation and loss in ΔΨm was observed. Additionally, major compounds identified were chosen for ligandprotein binding interaction studies to predict the molecular targets in colon cancer. It was observed that compounds such as 9-Octadecenoic acid;4H-1- Benzopyran-4-one, 3-(3,4-dimethoxyphenyl)-6,7- dimethoxy; 2-(4-Methoxy-2,6-dimethylphenyl) -3-methyl-2H-benzo [g]indazole and 2-Bornanol,5-(2,4- dinitro phenyl) hydrazono have a prominent binding affinity with NF-ΚB. This was also further validated by immuno-blotting results wherein CDEO treatment in colon cancer cells led to the abrogation of NFΚB, and the Bcl-2-associated X protein (Bax): B-cell lymphoma (Bcl)-2 ratio was up-regulated leading to enhanced cleaved caspase 3 formation and subsequent apoptosis. Conclusion: These results unveil CDEO inhibits cell proliferation and induces apoptosis in colon cancer cells, which can be attributed to the abrogation of the NFΚB signaling pathway.

Artificial receptor-like structures such as molecular imprinted polymers (MIPs) are biomimetic molecules are used to replicate target specific antibody-antigen mechanism. In MIPs, selective binding of template molecule can be significantly correlated with lock and key mechanism, which play a major role in the drug delivery mechanism. The MIPs are biocompatible with high efficiency and are considered in several drug delivery and biosensor applications besides continuous and controlled drug release leading to better therapeutics. There is a need to explore the potential synthetic methods to improve MIPs with respect to the imprinting capacity in cancer therapeutics. In this review, we focus on MIPs as drug delivery mechanism in cancer and the challenges related to their synthesis and applications.

Liver cancer is the fifth (6.3% of all cancers i.e., 548,000 cases/year) and ninth (2.8% of all cancers i.e., 244,000 cases/year) most prevalent cancer worldwide in men and women, respectively. Although multiple choices of therapies are offered for Hepatocellular Carcinoma (HCC) like liver resection or transplant, radiofrequency ablation, transarterial chemoembolization, radioembolization, and systemic targeted agent, by the time of diagnosis, most of the cases of HCC are in an advanced stage, which renders therapies like liver transplant or resection and local ablation impractical; and targeted therapy has its shortcomings like general toxicity, imprecise selectivity, several adversative reactions, and resistance development. Therefore, novel drugs with specificity and selectivity are needed to provide the potential therapeutic response. Various researches have shown the potential of phytomedicines in liver cancer by modulating cell growth, invasion, metastasis, and apoptosis. However, their therapeutic potential is held up by their unfavorable properties like stability, poor water solubility, low absorption, and quick metabolism. Nonetheless, the advancement of nanotechnology-based innovative nanocarrier formulations has improved the phytomedicines’ profile to be used in the treatment of liver cancer. Nanocarriers not only improve the solubility and stability of phytomedicines but also extend their residence in plasma and accomplish specificity. In this review, we summarize the advancements introduced by nanotechnology in the treatment of liver cancer. In particular, we discuss quite a few applications of nanophytomedicines like curcumin, quercetin, epigallocatechin-3-gallate, berberine, apigenin, triptolide, and resveratrol in liver cancer treatment.