Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.

Clausena excavata Burm.f. is a shrub traditionally used to treat cancer patients in Asia. The main bioactive chemical components of the plant are alkaloids and coumarins. In this study, we isolated clausenidin from the roots of C. excavata to determine its apoptotic effect on the colon cancer (HT-29) cell line. We examined the effect of clausenidin on cell viability, ROS generation, DNA fragmentation, mitochondrial membrane potential in HT-29 cells. Ultrastructural analysis was conducted for morphological evidence of apoptosis in the treated HT-29 cells. In addition, we also evaluated the effect of clausenidin treatment on the expression of caspase 3 and 9 genes and proteins in HT-29 cells. Clausenidin induced a G0/G1 cell cycle arrest in HT-29 cells with significant (p < 0.05) dose-dependent increase in apoptotic cell population. The DNA fragmentation assay also showed apoptotic features in the clausenidin-treated HT-29 cells. Clausenidin treatment had caused significant (p < 0.05) increases in the expression of caspase 9 protein and gene in HT-29 cells and mitochondrial ROS and mitochondrial membrane depolarization. The results suggest the involvement of the mitochondria in the caspase-dependent apoptosis in clausenidin-treated colon cancer cells. Clausenidin induces a caspase-dependent apoptosis in colon cancers through the stimulation of the mitochondria. The study demonstrates the potential of clausenidin for use in the treatment of colon cancers.

The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor α has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to study the binding affinities of small molecules from the Artocarpus species after their drug-like properties were ascertained. The structure of the ligand-binding domain of human Estrogen receptor α was retrieved from Protein Data Bank while the structures of compounds were collected from PubChem database. The binding interactions of the studied compounds were reported as well as their glide scores. The best glide scored ligand, was Artonin E with a score of −12.72 Kcal when compared to other studied phytomolecules and it evoked growth inhibition of an estrogen receptor positive breast cancer cells in submicromolar concentration (3.8–6.9 µM) in comparison to a reference standard Tamoxifen (18.9–24.1 µM) within the tested time point (24–72 h). The studied ligands, which had good interactions with the target receptor, were also drug-like when compared with 95% of orally available drugs with the exception of Artoelastin, whose predicted physicochemical properties rendered it less drug-like. The in silico physicochemical properties, docking interactions and growth inhibition of the best glide scorer are indications of the anti-breast cancer relevance of the studied molecules.

Andrographis paniculata (Burm.f.) Nees has been used traditionally in treating many diseases. This study investigated its potential to attenuate benign prostatic hyperplasia (BPH) in male rats. Rats were castrated, divided into five groups and orally treated for 14 days with: normal saline,10 mg/kg testosterone propionate sc, finasteride (0.5 mg/kg), 500 mg, and 1500 mg/kg of Andrographis paniculata. Relative prostate weights, the correlation between prostatic index and volume and the prostates' histopathology as well as Prostate Specific Antigen (PSA) were evaluated. Following treatment with Andrographis paniculata, the prostate weights were significantly reduced (p < 0.05) and the lost correlation observed in the untreated group was restored. Histopathological assessment showed reduced epithelial hyperplasia following treatment with a resultant thin layer of epithelial cells, similar to the healthy normal control group. The level of PSA was also reduced. Andrographis paniculata, thus, has the potential to inhibit the proliferation observed in testosterone-induced BPH.

Breast cancer is among the principal cause of cancer fatalities in women. Notwithstanding the use of chemotherapy and advances in drug delivery techniques, cancer-related morbidity and mortality are still increasing with the increase in resistance to known therapeutics. This dilemma has drastically reduced the rate of survival from this deadly disease, creating a dire need for new drugs, especially from natural sources that would exhibit similar or better anticancer properties while imparting minimal adverse side effects. Among the bewildering hallmark capabilities of cancer is the evasion of apoptosis while in its course to immortality. Thus, induction of apoptosis in cancerous cells is an important breakthrough that cannot be ignored. There are, however, two major pathways of apoptosis in mammals, viz., the death receptor–mediated pathway (extrinsic pathway) and the mitochondrial-mediated pathway (intrinsic pathway). Artonin E, a prenylated flavonoid isolated from the stem bark of Artocarpus elasticus, was seen to induce apoptosis in MCF-7 breast cancer cells, hence halting the breast cancer cells in their journey to immortality.

Background: Diabetes mellitus is a life-threatening disease associated with worsening of glycemic control, progressive metabolic dysfunctions and disruption of the Phosphatase and Tensin Homolog (PTEN) receptor. Purpose: To evaluate the effect of chloroquine on blood glucose level and lipid profile of alloxan-induced diabetic mice and to observe its interaction with PTEN, a negative regulator of insulin signaling pathway. Methodology: Thirty mice were used for the experiment. A group (n = 5) was kept as healthy control while the others were pre-treated with 140 mg/kg of alloxan monohydrate in distilled water. The alloxan-induced diabetic mice were randomly divided into four groups: diabetic model control group, 60 mg/kg chloroquine, 120 mg/kg chloroquine, and 10 mg/kg glibenclamide treatment groups respectively. Treatment was done once daily for seven days and the blood glucose level was investigated acutely and then daily throughout the experimental period. A molecular docking study was also conducted to evaluate the interaction of chloroquine with PTEN using PYRX software, while an automated COBAS C 311 machine was used to analyze the lipid profile after the treatment period. Results: Oral administration of chloroquine gradually and significantly lowered the raised blood glucose level in a time- and dose-dependent manner. A repeated study with 120 mg/kg of chloroquine revealed a decline in blood sugar from 221.5 ± 3.6 on day 1 to 85.5 ± 2.4 on day 7 in comparison to glibenclamide, whose sugar level was reduced to 75.5 ± 3.7 at the end of day 7. The docking study revealed a non-competitive inhibition with an inhibition score of -6.1 in comparison to metformin, which had a score of -4.4, and glibenclamide, which had a score of -9.0. This interaction resulted in a conformational change of the receptor, hence, enhancing glucose uptake and reducing the raised hyperglycemia. Treatment with chloroquine was also observed to reduce the total cholesterol and triglyceride levels from 162 in the model group to 144 and 141 to 116 mmol/L, respectively. The levels of low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein (VLDL) following treatment with chloroquine were not statistically different from the non-diabetic healthy mice. These values were very similar to those obtained with glibenclamide-treated diabetic mice. Conclusion: From the results, chloroquine possesses potent antidiabetic properties and can improve dyslipidemia imposed by hyperglycemia probably owing to its inhibition of PTEN, a negative regulator of insulin resistance.