Enhanced extracellular vesicles mediated uttroside B (Utt-B) delivery to Hepatocellular carcinoma cell: Pharmacokinetics based on PBPK modelling.

Our prior investigation has confirmed that the anti-hepatocellular carcinoma activity of the plant saponin, specifically Uttroside B (Utt-B), derived from the leaves of Solanum nigrum Linn. This study concentrated on formulating a novel biocompatible nanocarrier utilizing Extracellular vesicles (EVs) to enhance the delivery of plant saponin into cells. The physicochemical attributes of Extracellular Vesicles/UttrosideB (EVs/Utt-B) were comprehensively characterized through techniques such as Transmission Electron Microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR). Despite the promising therapeutic potential of this uttroside B, mechanistic know-how about its entry into cells is still in its infancy. Our research sheds light on the extracellular vesicle-mediated mechanism facilitating the entry of the saponin into cells, a phenomenon confirmed through the use of by confocal microscopy. We further analysed drug-releasing kinetics and simulated the Pharmacokinetics by PBPK modelling. The simulated pharmacokinetics revealed the bioavailability of Uttroside-B in oral administration against intravenous administration.

Phytochemicals as Potential Lead Molecules against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, accounting for 85-90% of liver cancer cases and is a leading cause of cancer-related mortality worldwide. The major risk factors for HCC include hepatitis C and B viral infections, along with chronic liver diseases, such as cirrhosis, fibrosis, and non-alcoholic steatohepatitis associated with metabolic syndrome. Despite the advancements in modern medicine, there is a continuous rise in the annual global incidence rate of HCC, and it is estimated to reach >1 million cases by 2025. Emerging research in phytomedicine and chemotherapy has established the anti-cancer potential of phytochemicals, owing to their diverse biological activities. In this review, we report the major phytochemicals that have been explored in combating hepatocellular carcinoma and possess great potential to be used as an alternative or in conjunction with the existing HCC treatment modalities. An overview of the pre-clinical observations, mechanism of action and molecular targets of some of these phytochemicals is also incorporated.

Targeting receptor tyrosine kinase signaling: Avenues in the management of cutaneous squamous cell carcinoma.

Non-melanoma skin cancer (NMSC) is the most frequently diagnosed cancer worldwide. Among the various types of NMSCs, cutaneous squamous cell carcinoma (cSCC) exhibits more aggressive phenotype and is also the second-most prevalent type. Receptor tyrosine kinases (RTK) triggers key signaling events that play critical roles in the development of various cancers including cSCC. Unsurprisingly, for this reason, this family of proteins has become the cynosure of anti-cancer drug discovery pipelines and is also being considered as attractive targets against cSCC. Though inhibition of RTKs in cSCC has yielded favourable results, there is still scope for bettering the therapeutic outcome. In this review, we discuss the relevance of RTK signaling in the progression of cutaneous squamous cell carcinoma, and observations from clinical trials that used RTK inhibitors against cSCC. Backed by results from preclinical studies, including those from our lab, we also give insights into the scope of using some natural products as effective suppressors of RTK signaling and skin carcinogenesis.

Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma.

We previously reported the remarkable potency of uttroside B (Utt-B), saponin-isolated and characterized in our lab from Solanum nigrum Linn, against HCC. Recently, the U.S. FDA approved Utt-B as an 'orphan drug' against HCC. The current study validates the superior anti-HCC efficacy of Utt-B over sorafenib, the first-line treatment option against HCC. The therapeutic efficacies of Utt-B vs. sorafenib against HCC were compared in vitro, using various liver cancer cell lines and in vivo, utilizing NOD.CB17-Prkdcscid/J mice bearing human HCC xenografts. Our data indicate that Utt-B holds an augmented anti-HCC efficacy over sorafenib. Our previous report demonstrated the pharmacological safety of Utt-B in Chang Liver, the normal immortalized hepatocytes, and in the acute and chronic toxicity murine models even at elevated Utt-B concentrations. Here, we show that higher concentrations of sorafenib induce severe toxicity, in Chang Liver, as well as in acute and chronic in vivo models, indicating that, apart from the superior therapeutic benefit over sorafenib, Utt-B is a pharmacologically safer molecule, and the drug-induced undesirable effects can, thus, be substantially alleviated in the context of HCC chemotherapy. Clinical studies in HCC patients utilizing Utt-B, is a contiguous key step to promote this drug to the clinic.

The emerging role of selenium metabolic pathways in cancer: New therapeutic targets for cancer.

Selenium (Se) is incorporated into the body via the selenocysteine (Sec) biosynthesis pathway, which is critical in the synthesis of selenoproteins, such as glutathione peroxidases and thioredoxin reductases. Selenoproteins, which play a key role in several biological processes, including ferroptosis, drug resistance, endoplasmic reticulum stress, and epigenetic processes, are guided by Se uptake. In this review, we critically analyze the molecular mechanisms of Se metabolism and its potential as a therapeutic target for cancer. Sec insertion sequence binding protein 2 (SECISBP2), which is a positive regulator for the expression of selenoproteins, would be a novel prognostic predictor and an alternate target for cancer. We highlight strategies that attempt to develop a novel Se metabolism-based approach to uncover a new metabolic drug target for cancer therapy. Moreover, we expect extensive clinical use of SECISBP2 as a specific biomarker in cancer therapy in the near future. Of note, scientists face additional challenges in conducting successful research, including investigations on anticancer peptides to target SECISBP2 intracellular protein.