Nerolidol, Bioactive Compound Suppress Growth of HCT-116 Colorectal Cancer Cells Through Cell Cycle Arrest and Induction of Apoptosis.

Colon cancer is the most prevalent cancer and causes the highest cancer-associated mortality in both men and women globally. It has a high incidence and fatality rate, which places a significant burden on the healthcare system. The current work was performed to understand the beneficial roles of nerolidol on the viability and cytotoxic mechanisms in the colon cancer HCT-116 cells. The MTT cytotoxicity assay was done to investigate the effect of nerolidol at different doses (5-100 µM) on the HCT-116 cell viability. The impacts of nerolidol on ROS accumulation and apoptosis were investigated using DCFH-DA, DAPI, and dual staining assays, respectively. The flow cytometry analysis was performed to study the influence of nerolidol on the cell cycle arrest in the HCT-116 cells. The outcomes of the MTT assay demonstrated that nerolidol at different doses (5-100 µM) substantially inhibited the HCT-116 cell viability with an IC50 level of 25 µM. The treatment with nerolidol appreciably boosted the ROS level in the HCT-116 cells. The findings of DAPI and dual staining revealed higher apoptotic incidences in the nerolidol-exposed HCT-116 cells, which supports its ability to stimulate apoptosis. The flow cytometry analysis demonstrated the considerable inhibition in cell cycle at the G0/G1 phase in the nerolidol-exposed HCT-116 cells. Our research showed that nerolidol can inhibit the cell cycle, increase ROS accumulation, and activate apoptosis in HCT-116 cells. In light of this, it may prove to be a potent and salutary candidate to treat colon cancer.

Anticancer effect of selenium/chitosan/polyethylene glycol/allyl isothiocyanate nanocomposites against diethylnitrosamine-induced liver cancer in rats.

Background: Nano-based drug delivery systems have shown several advantages in cancer treatment like specific targeting of cancer cells, good pharmacokinetics, and lesser adverse effects. Liver cancer is a fifth most common cancer and third leading cause of cancer-related mortalities worldwide. Objective: The present study focusses to formulate the selenium (S)/chitosan (C)/polyethylene glycol (Pg)/allyl isothiocyanate (AI) nanocomposites (SCPg-AI-NCs) and assess its therapeutic properties against the diethylnitrosamine (DEN)-induced liver cancer in rats via inhibition of oxidative stress and tumor markers. Methodology: The SCPg-AI-NCs were synthesized by ionic gelation technique and characterized by various characterization techniques. The liver cancer was induced to the rats by injecting a DEN (200 mg/kg) on the 8th day of experiment. Then DEN-induced rats treated with 10 mg/kg of formulated SCPg-AI-NCs an hour before DEN administration for 16 weeks. The 8-hydroxy-2' -deoxyguanosine (8-OHdG) content, albumin, globulin, and total protein were examined by standard methods. The level of glutathione (GSH), vitamin-C & -E, and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities were examined using assay kits. The liver marker enzymes i.e., alanine transaminase (ALT), aspartate tansaminase (AST), γ-glutamyl transaminase (GGT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) activities, alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA), Bax, and Bcl-2 levels, and caspase-3&9 activities was examined using assay kits and the liver histopathology was assessed microscopically by hematoxylin and eosin staining method. The effect of formulated SCPg-AI-NCs on the viability and apoptotic cell death on the HepG2 cells were examined using MTT and dual staining assays, respectively. Results: The results of different characterization studies demonstrated the formation of SCPg-AI-NCs with tetragonal shape, narrowed distribution, and size ranging from 390 to 450 nm. The formulated SCPg-AI-NCs treated liver cancer rats indicated the reduced levels of 8-OHdG, albumin, globulin, and total protein. The SCPg-AI-NCs treatment appreciably improved the GSH, vitamin-C & -E contents, and SOD, CAT, GPx, and GR activities in the serum of liver cancer rats. The SCPg-AI-NCs treatment remarkably reduced the liver marker enzyme activities in the DEN-induced rats. The SCPg-AI-NCs treatment decreased the AFP and CEA contents and enhanced the Bax and caspase 3&9 activities in the DEN-induced rats. The SCPg-AI-NCs effectively decreased the cell viability and induced apoptosis in the HepG2 cells. Conclusion: The present findings suggested that the formulated SCPg-AI-NCs remarkably inhibited the DEN-induced liver carcinogenesis in rats. These findings provide an evidence that SCPg-AI-NCs can be a promising anticancer nano-drug in the future to treat the liver carcinogenesis.

Influence of Padina gymnospora on Apoptotic Proteins of Oral Cancer Cells-a Proteome-Wide Analysis.

Oral carcinoma is one of the most vicious forms of cancer with a very low survival rate, as its patients often respond poorly to conventional chemotherapy. Presently several researchers are attempting to pursue an alternative to this therapy using natural products. Considering the promising strategy and induction of apoptosis to target the cancer cells, we evaluated the influence of a seaweed Padina gymnospora (15 µg/ml and 20 µg/ml) in enhancing apoptosis of oral cancer cells (KB-CHR-8-5) after 24-h incubation. The morphological changes indicating apoptosis were primarily assessed using a light microscope after which the apoptosis was confirmed by performing AO/EB staining method. Subsequently, MMP and ROS levels in the cells were assessed using Rh 123 and DCFH-DA staining procedures, respectively. All the above tests confirmed the ability of P. gymnospora to accelerate apoptosis in the oral cancer cells. As a next step, wide proteome analysis was performed where the proteins from P. gymnospora-treated cells were separated using the 2D electrophoresis technique and compared with that of control cells to isolate the differentially expressed proteins. This procedure resulted in the isolation of 10 proteins which were identified using MALDI-TOF/TOF MS, which established that most of the isolated proteins were part of the apoptotic process of the cell. The proteins identified are part of huge and complex pathways where it gets linked with many more genes which are also associated with apoptosis. Bioinformatics of these identified proteins was analyzed using STRING and PANTHER databases. These proteins contribute to cell apoptosis by affecting various functions, biological processes, and the synthesis of cellular components. PANTHER also demonstrated that these proteins belong to the classes of proteins that take part in several vital pathways of the cell among which the apoptotic pathway is the predominant one.

Chemopreventive effect of myrtenal on bacterial enzyme activity and the development of 1,2-dimethyl hydrazine-induced aberrant crypt foci in Wistar Rats.

Colon cancer remains as a serious health problem around the world despite advances in diagnosis and treatment. Dietary fibers are considered to reduce the risk of colon cancer as they are converted to short chain fatty acids by the presence of anaerobic bacteria in the intestine, but imbalanced diet and high fat consumption may promote tumor formation at different sites, including the large bowel via increased bacterial enzymes activity. The present study was conducted to characterize the inhibitory action of myrtenal on bacterial enzymes and aberrant crypt foci (ACF). Experimental colon carcinogenesis induced by 1,2-dimethylhydrazine is histologically, morphologically, and anatomically similar to human colonic epithelial neoplasm. Discrete microscopic mucosal lesions such as ACF and malignant tumors function as important biomarkers in the diagnosis of colon cancer. Methylene blue staining was carried out to visualize the impact of 1,2-dimethylhydrazine and myrtenal. Myrtenal-treated animals showed decreased levels of bacterial enzymes such as ß-glucuronidase, ß-glucosidase, and mucinase. Characteristic changes in the colon were noticed by inhibiting ACF formation in the colon. In conclusion, treatment with myrtenal provided altered pathophysiological condition in colon cancer-bearing animals with evidence of decreased crypt multiplicity and tumor progression.

Anti-Oxidative Effect of Myrtenal in Prevention and Treatment of Colon Cancer Induced by 1, 2-Dimethyl Hydrazine (DMH) in Experimental Animals

Colon cancer is considered as the precarious forms of cancer in many developed countries, with few to no symptoms; the tumor is often diagnosed in the later stages of cancer. Monoterpenes are a major part of plant essential oils found largely in fruits, vegetables and herbs. The cellular and molecular activities show therapeutic progression that may reduce the risk of developing cancer by modulating the factors responsible for colon carcinogenesis. Colon cancer was induced with DMH with a dose of (20 mg/Kg/body weight) for 15 weeks by subcutaneous injection once in a week. Myrtenal treatment was started with (230 mg/Kg/body weight) by intragastric administration, one week prior to DMH induction and continued till the experimental period of 30 weeks. The Invivo results exhibit the elevated antioxidant and lipid peroxidation levels in DMH treated animals. The Histopathological analysis of colon tissues well supported the biochemical alterations and inevitably proves the protective role of Myrtenal. Treatment with myrtenal to cancer bearing animals resulted in a remarkable increase in the inherent antioxidants and excellent modulation in the morphological and physiological nature of the colon tissue. It is thus concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of colon carcinoma in Wistar albino rats.

Exposure to polycyclic aromatic hydrocarbons with special focus on cancer

Polycyclic aromatic hydrocarbons (PAHs) are a group of compounds consisting of two or more fused aromatic rings. Most of them are formed during incomplete combustion of organic materials such as wood and fossil fuels, petroleum products, and coal. The composition of PAH mixtures varies with the source and is also affected by selective weathering effects in the environment. PAHs are ubiquitous pollutants frequently found in a variety of environments such as fresh water and marine sediments, the atmosphere, and ice. Due to their widespread distribution, the environmental pollution due to PAHs has aroused global concern. Many PAHs and their epoxides are highly toxic, mutagenic and/or carcinogenic to microorganisms as well as to higher forms of life including humans. The main aim of this review is to provide contemporary information on PAH sources, route of exposure, worldwide emission rate, and adverse effects on humans, especially with reference to cancer.

Myrtenal ameliorates diethylnitrosamine-induced hepatocarcinogenesis through the activation of tumor suppressor protein p53 and regulation of lysosomal and mitochondrial enzymes.

Myrtenal is a novel class of compound belongs to monoterpenes found predominantly in mint, pepper, etc., and it was shown to have excellent pharmacological activities against many diseases among which cancer is imperative. Hepatocellular carcinoma is a primary malignancy of the hepatocytes, which rapidly leads to death in short periods. The aim of this study was to investigate the possible therapeutic efficiency of myrtenal against diethylnitrosamine-induced experimental hepatocarcinogenesis by analyzing the key enzymes of carbohydrate metabolism, lysosomal and mitochondrial TCA cycle enzymes, and also the possible role of tumor suppressor protein p53, and scanning electron microscopic studies. The results revealed that myrtenal significantly ameliorated the altered enzymes of carbohydrate metabolism, lysosomal and mitochondrial enzymes, and interestingly the tumor suppressor protein p53 was found to be significantly accumulated in myrtenal-treated animals, which inevitably confirms that myrtenal has a prominent role in preventing the liver cancer during treatment. Furthermore, the antineoplastic property was well evidenced by the mRNA expression of p53 protein by the reverse-transcriptase polymerase chain reaction and immunoblot analysis. The observed anticancer property of myrtenal may be due to the involvement and expression of p53 and influence in the mitochondrial and lysosomal membrane integrity and also interference in the gluconeogenesis process of cancer cells. Our results suggest that myrtenal is very efficient and useful compound in the treatment of liver cancer in future.