In silico analysis of molecular interactions between the anti- apoptotic protein survivin and dentatin, nordentatin, and quercetin

Survivin is a member of the inhibitor of apoptosis (IAP) family and is reportedly overexpressed in various types of human malignancies. Because the phytochemical compounds dentatin, nordentatin, and quercetin have demonstrated antiproliferative effects in various cancer cell lines, we compared their binding affinities for survivin in silico. Molecular docking analyses were performed using PyMol, Discovery Studio Biovia 2017, AutoDock Vina, and AutoDock Tools version 1.5.4. These computations indicated greater survivin binding affinity of quercetin (ΔG −7.0 kcal/mol) than nordentatin and dentatin (ΔG −6.5 and −5.5 kcal/mol, respectively), but suggest that all three compounds act as ligand inhibitors of survivin. The present data warrant validation using in vitro and in vivo assays

Stochastic modelling of the oral cancer proliferation and death in the presence of Thymoquinone as anticancer therapeutics

Oral cancer is one of the most commonly known cancer worldwide. Thymoquinone (TQ) an extract from Nigella sativa, has clinically been proven as an anticancer therapeutic agent for oral cancer due to its intrinsic pharmacological characteristics. Understanding the mechanisms of oral cancer proliferation and death in the presence of TQ is crucial so that the insight of the interaction of cancer cells and TQ can be discovered. Cancer cells in the presence of TQ is subjected to the uncontrolled factors of the environmental noise. Deterministic model is inadequate to explain this behaviour. Herein, a stochastic model is proposed to illustrate the dynamics of HSC-3 oral cancer cell lines in the presence of TQ. The deterministic model is perturbed with the noisy behaviour which then leads to the stochastic model. The model is simulated by using a four-stage stochastic Runge-Kutta (SRK4) method and the kinetic parameters are estimated by using the maximum likelihood estimation (MLE) method. The prediction quality of the model is measured by using root mean square error (RMSE). The low values of RMSE show the best-fit of the stochastic model

In vitro evaluation of the effect of Pluchea indica extracts in promoting glucose consumption activity on a liver cell line

Background: Type 2 diabetes mellitus is a chronic metabolic disorder that is associated with mortality and morbidity. Recently, several plant-based agents have been used in the management of diabetes. Pluchea indica has been traditionally consumed as a medicinal plant in Southeast Asia, and its leaves have demonstrated induction of hypoglycemic effect in normal rats. This in vitro study aimed to evaluate the potency of P. indica extracts in stimulating glucose consumption in human liver CCL-13 cell line model. Methods: P. indica leaves were dried and extracted using a series of organic solvents and water. The effect of the extracts on cell viability was determined by MTT assay. The glucose consumption was analyzed using glucose oxidase method. Results: Our results revealed that the methanol extract of P. indica could significantly increase glucose consumption of cells in a concentration-dependent manner, which suggests the usefulness of the extract as an antidiabetic candidate via stimulation of glucose uptake into the liver cells. Conclusion: Our study suggests that P. indica is a potential natural candidate for diabetes mellitus management

Therapeutic implications of thymoquinone and its molecular and functional mechanisms against oral and lung cancer

Thymoquinone, a bioactive component of the black seed of Nigella sativa, has received great attention from researchers due to its wide spectrum of pharmacological potentials. The present review highlights the molecular and functional mechanisms of thymoquinone serving as a therapeutic molecule combating oral and lung cancer by following the most recent literature. This summarized the latest nanotechnological interventions enhancing the efficacy and availability of thymoquinone in the in-vitro and in-vivo cancer models. Thymoquinone exhibits a significantly promising anticancer effect against oral and lung cancer by prompting intrinsic and extrinsic pathways of apoptosis through the activation of different caspases cascades, up and downregulation of apoptotic genes, antitumor cell proliferation, ROS regulation, etc. The accomplished insight into molecular and functional mechanisms of thymoquinone particularly combating oral and lung cancer will provide a better understanding and exploration of thymoquinone in an ethnopharmacological context

Prediction on binding affinity of nordentatin and quercetin against anti-apoptotic BCL-2 protein

Targeting apoptotic cell-death pathways has been a subject of growing interest in discovery of novel anti-cancer agents. Bcl-2 is a member of Bcl-2 family protein that is crucial for cell survival by supressing apoptosis and its overexpression is frequently detected in many type of cancers. Inactivation of Bcl-2 has been considered as an ideal strategy in anti-cancer therapies. A large number of bioactive compounds derived from natural source including Nordentatin and Quercetin have been reported to possess anticancer activities. Here we report the binding affinities of Nordentatin and Quercetin in silico against anti-apoptotic Bcl-2 protein using molecular docking programs. We demonstrate for the first time that Nordentatin showed optimum binding affinity with Bcl-2, similar to those shown by Quercetin. As the Quercetin has been previously known to play a role in cancer cell apoptosis through down-regulation of Bcl-2, the result indicated that Nordentatin could also be proposed as a prospective anticancer molecule via inhibition of Bcl-2 protein

Enhancement of Cisplatin Cytotoxicity in Combination With Thymoquinone on Oral Cancer HSC-4 Cell Line

Abstract. Cisplatin (CDDP) is frequently used as an adjuvant chemotherapy in oral cancer management and often associated with significant adverse effects. Natural occurring compounds have provided considerable value in cancer chemotherapeutic research. Thymoquinone (TQ), the main constituent of Nigella sativa has been widely known for its anti-neoplastic activities with negligible undesirable effect on normal cells. The purpose of this study was to investigate the enhancement of CDDP cytotoxicity in combination with TQ oral cancer HSC-4 cell line. Cytotoxicity assay followed by Isobologram and Combination Index (CI) analysis using CompuSyn software demonstrated that combined exposure of 1.66 µM (‘low-dose’) of CDDP and 1.52 µM of TQ exhibited synergism on HSC-4 cells with CI value <1 (0.362 and 0.538 at 24h and 48h, respectively). In addition, it was revealed that the low CDDP dose used in the assay was sufficient to reduce the percentage of viable HSC-4 cells at the level comparable to those exposed to IC50 dose of CDDP alone (16.9 µM and 1.97 µM at 24h and 48h respectively). The cytotoxicity assay also confirmed that CDDP treatment at the low-dose had no effect on human oral fibroblasts viability. The study indicates the potential use of TQ to augment the chemotherapeutic activities of CDDP against oral cancers while minimizing the CDDP toxic side effects on normal cells

Pluchea indica extracts stimulates insulin secretion through enhancement of Irs2 and Glut2 genes expression in RIN-5F pancreatic β-cells

Diabetes mellitus (DM) is a chronic metabolic disorder that has reached epidemic proportions with the estimated prevalence rates and trends are escalating largely in developing countries. The awareness of the modern drugs to treat DM which have numerous side effects has led to a recent growing interest in the therapeutic use of natural products, especially those derived from plants. Pluchea indica is abundantly distributed in Malaysia and it is traditionally claimed to have antidiabetic properties. Our previous in vivo study demonstrated that P. indica prevents hyperglycemia in streptozotocin-induced diabetic rats and reduce blood glucose in normal rats. Here we report for the first time the antidiabetic potential of P. indica in the insulin regulation through cell-based in vitro model by using RIN-5F pancreatic β-cells. P. indica was extracted from the powdered dry leaves using soxhlet apparatus with n-hexane, dichloromethane, ethyl acetate and methanol consecutively. The plant also was macerated using water to yield water extract. The maximum tolerable concentration of extracts on RIN-5F pancreatic β-cells was determined by MTT assay. The concentration of 0.2 mg/mL was found to be the maximum concentration of P. indica extracts in the absence of cytotoxicity. The insulin released was measured by a rat insulin enzyme-linked immunoassay (ELISA) system. We found that hexane and water extracts at concentration of 0.05 mg/mL and 0.1 mg/mL respectively stimulated insulin release (p<0.05). Moreover, the insulin stimulation was associated with elevated expression of Insulin receptor substrate 2 (Irs2) and glucose-transporter Glut2 genes as determined by Quantitative Reverse Transcription PCR (qRT-PCR). Taken together, these findings indicate dual positive action of P. indica as a candidate anti-diabetic drug from natural sources by stimulating insulin secretion in β-cells. These findings provide the following insights for future research in exploring the potential clinical usefulness of P. indica for diabetes management

Stochastic modelling of the oral cancer proliferation and death in the presence of Thymoquinone as anticancer therapeutics

Oral cancer is one of the most commonly known cancer worldwide. Thymoquinone (TQ) an extract from Nigella sativa, has clinically been proven as an anticancer therapeutic agent for oral cancer due to its intrinsic pharmacological characteristics. Understanding the mechanisms of oral cancer proliferation and death in the presence of TQ is crucial so that the insight of the interaction of cancer cells and TQ can be discovered. Cancer cells in the presence of TQ is subjected to the uncontrolled factors of the environmental noise. Deterministic model is inadequate to explain this behaviour. Herein, a stochastic model is proposed to illustrate the dynamics of HSC-3 oral cancer cell lines in the presence of TQ. The deterministic model is perturbed with the noisy behaviour which then leads to the stochastic model. The model is simulated by using a four-stage stochastic Runge-Kutta (SRK4) method and the kinetic parameters are estimated by using the maximum likelihood estimation (MLE) method. The prediction quality of the model is measured by using root mean square error (RMSE). The low values of RMSE show the best-fit of the stochastic model

Anti-neoplastic potential of ethyl-p-methoxycinnamate of Kaempferia galanga on oral cancer cell lines

Kaempferia galanga is one of the herbal plant that have many medicinal properties. The plant extract has also been reported to possess in vitro anti-cancer activities on various cancer cell lines such as human colon cancer SW620, cervical cancer C33A, and breast cancer MCF-7 cell lines. Ethyl-p-methoxycinnamate (EPMC), a major constituent of volatile oil of Kaempferia galanga has been attributed to its medicinal benefits. We report here for the first time the anticancer potential of EPMC on oral cancer cells derived from human oral cavity, HSC-3 and Ca922 lines. MTT assay results showed that EPMC markedly induced cytotoxicity on HSC-3 (IC50 0.075 mg/mL) and Ca922 (IC50 0.085 mg/mL) cell lines. The apoptotic activity induced by EPMC was detected in both cell lines by flow cytometry and confirmed with Caspase 3/7 assay. Moreover, quantitative RT-PCR analysis revealed that EPMC-induced apoptosis in both lines elevated the mRNA levels of pro-apoptotic genes caspase-9 and PUMA. These results suggest that EPMC may be a potential candidate for oral cancer treatment

In Vitro Wound Healing Effect of Asiaticoside Extracted from Centella asiatica (‘Pegaga’) on Human Gingival Fibroblast Cell Line

Abstract. Asiaticoside is a bioactive compound found in the traditional plant Centella asiatica (Asiatic pennywort or ‘Pegaga’) generally used for wound healing applications. Numerous studies have discussed the potential benefits of asiaticoside on different human cells such as keratinocytes and dermal fibroblast cells in healing of wounds. However only very few studies have been conducted to investigate its healing effect on cells originated from human oral cavity. The present study aimed to determine the potential of asiaticoside on human gingival fibroblast cells. Cytotoxic activities of the compounds were assessed by MTT assay. The wound healing was examined by scratch assay. The effect of asiaticoside on Col1A1 gene expression was also analyzed using qRT-PCR. Col1A1 is known to play a crucial role in wound healing. The MTT assay result showed that the maximum tolerable concentration of asiaticoside was 0.25 mg/ml. The scratch assay revealed that asiaticoside significantly accelerated the wound healing compared to the negative control (P<0.05). Moreover, the qRT-PCR demonstrated that asiaticoside markedly increased Col1A1 mRNA expression. These results proved asiaticoside as a potential candidate for wound healing agent in dentistry