Clinical Cancer Drugs - Volume 10, Issue 1, 2024

NSCLC is the predominant form of lung cancer, often exhibiting resistance to chemotherapy. Thymol and citral have shown promise as anticancer agents in different cancer cell lines but have not been evaluated in combination against NSCLC. Hence, we planned to investigate the anticancer effect of thymol-citral combination and explore its mechanisms of action against A549 cells.

A549 cells were exposed to varying concentrations of thymol and citral, alone and in combination. Cell proliferation, plasma membrane integrity, apoptotic markers, reactive oxygen species (ROS) levels, cell cycle distribution, senescence induction, and migration potential were assessed. Additionally, in vitro safety was evaluated in human buccal epithelial cells (HBECs) and human red blood cells (RBCs).

Thymol and citral showed synergistic action against A549 cells, with a CI value of 0.75. After 24 h, they induced apoptosis, caused G0/G1 phase arrest, and increased ROS levels, suggesting oxidative stress as the mechanism. This combination also induced cell senescence, significantly inhibited A549 cell migration, and was non-toxic to human RBCs and HBECs.

Overall, the thymol-citral synergistic combination was found to be a safe and effective therapy option for non-small cell lung cancer.

The Wnt/beta-catenin pathway is one of the pathways that is deregulated in pancreatic cancer and is reported to be associated with a poor prognosis. This indicates the need for the identification of novel agents to improve the efficacy of current therapy or have an improved efficacy. Therefore, in the present study, we explored the anticancer activity of PNU-74654 alone or in combination with gemcitabine in 2 and 3-dimensional cell culture models of pancreatic cancer.

The MTT assay was carried out to determine the viability of PC cancerous cells (PCCs), while the cytotoxicity of this agent was evaluated in a 3D cell culture model (spheroid). The effects of PNU-74654 were investigated in established cell migration/invasion assays.

The expression of candidate genes affecting the cell cycle, migration, and Wnt/b-catenin pathway was evaluated at mRNA and/or proteins by RT-PCR or Western blot. PNU-74654 inhibited the cell growth at IC50 of 122 ± 0.4 umol/L and had a synergistic effect on the antiproliferative properties of gemcitabine by modulating the Wnt pathway. The PNU-74654/gemcitabine combination reduced the migratory and invasiveness of PC cells, compared to control cells, through perturbation of E-cadherin.

Our findings demonstrate the profound antitumor properties of PNU-74654 in in vitro models of pancreatic cancer, supporting further in vivo studies to evaluate the therapeutic impact of this novel therapy to target the Wnt pathway in the treatment of pancreatic cancer.

The present research work aims to formulate a cost-effective and less toxic drug for specific and selective delivery at the tumor site.

Existing therapeutics, such as chemo, surgery, etc., for fast-paced MCF-7 breast cancer, still face challenges, especially due to their toxic side effects. The unique properties of metal nanoparticles embedded in anti-oxidant plant polymers have sparked great interest in the formulation of less toxic-targeted drugs for cancer cure.

The present work aims to synthesize a targeted formulation of colloidal nanosilver by surface engineering of silver nanoparticles using plant polymers in electrolytic deposition technique, developed indigenously at the institute lab.

A current is passed through an elctrolyte, AgNO3, which splits it into ions. The positive ions of Ag deposit over LDPE wrapped carbon cathode and negative ion, NO3, is liberated. Ag⁺ ions get capped in-situ. These surface-modified silver nanoparticles formulate a colloidal solution. UV-visible and FTIR spectroscopy, TEM-EDX, and XRD were used to validate as-prepared formulation and in vivo human tumor xenograft model in NOD-SCID mouse for efficacy against MCF-7 breast cancer.

The as-synthesized formulation consists of pure spherical poly-dispersed silver nanoparticles of average size 5.4 nm, coated with sulphated flavanols. The efficacy evaluation reported that it significantly, T/C = 0.53, reduced tumor volumes with a 100% survival rate and change in animal body weight <4 gms.

The as-synthesized formulation can be used as a potential neo-adjuvant or adjuvant drug along with existing therapeutics for MCF-7 breast cancer, significantly reducing the toxicity and cost.

Lymphatic transport is indispensable for maintaining tissue homeostasis and orchestrating immune surveillance. However, its association with solid tumor development and dissemination poses a paradox. While initially perceived as a passive conduit for metastasis, recent research highlights the active involvement of lymphatic vessels in tumor progression, inflammation, and immune surveillance.

This study aims to elucidate the active mechanisms underlying lymphatic transport's contribution to peripheral tissue immunity and its dual role in tumor-associated immune responses. Additionally, it explores emerging areas of interest in targeted cancer immunotherapy.

A comprehensive literature review was conducted to gather insights into the role of lymphatic transport in both physiological and pathological contexts, with a focus on cancer progression and immune modulation. Relevant studies and reviews were analyzed to provide current understanding and identify future directions in cancer immunotherapy.

Lymphatic vessels actively shape their transport function to influence peripheral tissue immunity, facilitating immune cell trafficking and antigen drainage. However, tumor-associated lymphatic remodeling disrupts this balance, promoting tumor dissemination and fostering a pro-tumorigenic microenvironment. Emerging research implicates lymphatic vessels in the formation of tertiary lymphoid structures, immune surveillance in the central nervous system, and interactions with the microbiome, obesity, and aging, highlighting their multifaceted role in cancer immunity.

Insights gained in lymphatic biology offer promising avenues for enhancing cancer immunotherapy by targeting lymphatic vessels and their transport function. A comprehensive understanding of lymphatic involvement in cancer pathogenesis supports its integration into therapeutic strategies to optimize immune surveillance and improve patient outcomes.

Newer chemical entities are created and synthesis has been made feasible by a variety of computer-aided drug design (CAAD) techniques. In addition to facilitating the visualisation of the ligand-target binding process, the application of in silico methodologies and structure-based drug design (SBDD) allows for the prediction of receptor affinities and significant binding pocket locations.

The goal of the current study was to identify new quinoline derivatives by computational methods specially designed to bind the EGFR receptor in the treatment of breast cancer.

ChemAxon Marvin Sketch 5.11.5 was used to create derivatives of quinolines. The admetSAR online web tools and SwissADME were utilised to forecast the toxicity and pharmacokinetic characteristics of several substances. A multitude of software programmes, such as Autodock 1.1.2, MGL Tools 1.5.6, Procheck, Protparam ExPasy tool, PyMOL, and Biovia Discovery Studio Visualizer v20.1.0.19295 were also employed to ascertain the ligand-receptor interactions between quinoline derivatives and the target receptor (PDB -5GNK).

Almost all components were shown to be less hazardous, orally consumable and to have the appropriate pharmacokinetic characteristics based on in silico study. All newly generated derivative compounds have higher docking scores when compared to the widely used medication sorafenib.

Interactions with quinoline analogues boost binding energy and the number of H-bonds produced, making them a suitable place to start when creating compounds for further exploration. The quinoline moiety increases its potential as a novel therapy alternative for breast cancer and could facilitate more comprehensive in vivo, in vitro, chemical-based, and pharma studies by medicinal chemists.

Cyclooxygenase-2 (COX-2) is induced in response to proinflammatory conditions, and it is not only a key enzyme in the inflammatory process, but also seems to be highly expressed in various types of cancer cells. On the other hand, it is well documented that chemical compounds with spiro scaffolds in their structure could be effective chemical agents against cancer types.

In this study, the cytotoxicity effects of spiroisoxazoline derivatives containing a spiro-bridge of naphthalinone and chromanone were investigated.

The cytotoxicity effects of compounds 7a-7h were evaluated by performing the MTT assay on the HT-29 (colorectal cancer), MCF-7 (breast cancer), and HEK-293 (normal kidney) cell lines. After that, a compound with high yield and remarkable cytotoxic activity was selected to analyze the cell cycle and apoptosis mechanism.

The most effective cytotoxic activity was observed on HT-29 and MCF-7 cell lines of compounds 7b (IC50 value: 1.07±0.28 µM) and 7f (IC50 value: 11.92±1.07 µM). None of the compounds had a toxic effect on normal HEK-293 cells, except for compound 7g with an IC50 value of 21.30±16.14 µM, whose effect was much lower than that of cisplatin and doxorubicin, known as anti-cancer agents. Subsequently, compound 7e with significant yield and cytotoxic activity was investigated to evaluate cell cycle and apoptosis. The result showed that compound 7e induced significant G0/G1 cell cycle arrest and apoptosis in HT-29 cells.

The selective COX-2 inhibitor compounds with spiroisoxazoline core structure could be suitable scaffolds for cytotoxic effects.