Liposome encapsulated anticancer drugs on autophagy in cancer cells - Current and future perspective.

Autophagy act as a double-edged sword in cancer with both tumor promoting and inhibiting roles. Under normal conditions of autophagy, the damaged cell organelles and other debris degrade inside the lysosome to provide energy and macromolecular precursors. However, enhanced autophagy can lead to apoptosis and programmed cell death highlighting its significance in cancer therapy. Liposome-based drug delivery systems for treating cancer patients have significant advantages over their non-formulated or free drug counterparts which could be effectively used to manipulate autophagy pathway in cancer patients. In the current review, drug uptake by the cells and its role in autophagy-mediated cancer cell death are discussed. Besides, the challenges and translational difficulties associated with the use of liposome-based chemotherapeutic drugs in clinical trials and in biomedical applications are also discussed.

Autophagy and cancer: Can tetrandrine be a potent anticancer drug in the near future?

Autophagy is an essential catabolic process in mammalian cells to maintain cellular integrity and viability by degrading the old and damaged cell organelles and other contents with the help of lysosomes. Deregulation in autophagy can be one of the major contributors leading to the continuous cell proliferation and development of tumors. Tetrandrine, a bisbenzylisoquinoline alkaloid known to have potent bioactivities such as anticancer, antimicrobial, anti-inflammatory, antidiabetic, antioxidant, immunosuppressive, cardiovascular, and calcium channel blocking effects. The present review evaluated the effectiveness of tetrandrine in targeting key proteins in the autophagy pathway to induce anticancer effect based on the available literature. An attempt is also made to understand the influence of tetrandrine in regulating autophagy by mTOR dependant and mTOR-independent pathways. In addition, the review also highlights the limitations involved and future perspectives in developing tetrandrine as a chemotherapeutic drug to treat cancer.

Tetrandrine isolated from Cyclea peltata induces cytotoxicity and apoptosis through ROS and caspase pathways in breast and pancreatic cancer cells.

Tetrandrine is a bisbenzylisoquinoline alkaloid known to exhibit anticancer activity against different cancers. In the present study, the cytotoxic effect of tetrandrine isolated from Cyclea peltata on pancreatic (PANC-1) and breast (MDA-MB-231) cancer cells was evaluated in vitro with an attempt to understand the role of tetrandrine on the generation of reactive oxygen species (ROS) and caspase activation. Results demonstrate the dose- and time-dependant cytotoxic effect of tetradrine on both MDA-MB-231 and PANC-1 cells with IC50 values ranging between 51 and 54 µM and 22 and 27 µM for 24 h and 48 h of incubation respectively. In addition, treatment of MDA-MB-231 and PANC-1 cells with tetrandrine showed the shrunken cytoplasm and damaged cell membrane in a dose- and time-dependant manner under the microscope. Also, tetrandrine treatment revealed an elevated levels of reactive oxygen species and increased activities of caspase-8, -9 and -3 confirming the apoptosis of cells through both extrinsic death receptor and intrinsic caspase activation. Therefore, the present study suggests the apoptosis of cells with the activation of caspase pathways mainly intrinsic pathway as a downstream event of tetrandrine-induced ROS generation. Hence, reactive oxygen species-mediated caspase activation pathway may be potentially targeted with the use of tetrandrine to treat breast and pancreatic cancers.

Tetrandrine--A molecule of wide bioactivity.

Stephania tetrandra and other related species of Menispermaceae form the major source of the bisbenzylisoquinoline alkaloid - tetrandrine. The plant is extensively referenced in the Chinese Pharmacopoeia for its use in the Chinese medicinal system as an analgesic and diuretic agent and also in the treatment of hypertension and various other ailments, including asthma, tuberculosis, dysentery, hyperglycemia, malaria, cancer and fever. Tetrandrine, well-known to act as a calcium channel blocker, has been tested in clinical trials and found effective against silicosis, hypertension, inflammation and lung cancer without any toxicity. Recently, the efficacy of tetrandrine was tested against Mycobaterium tuberculosis, Candida albicans, Plasmodium falciparum and Ebola virus. Tetrandrine's pharmacological property has been proved to be through its action on different signalling pathways like reactive oxygen species, enhanced autophagic flux, reversal of multi drug resistance, caspase pathway, cell cycle arrest and by modification of calcium channels. The present review summarises current knowledge on the synthesis, distribution, extraction, structural elucidation, pharmacological properties and the mechanism of action of tetrandrine. Future perspectives in the clinical use of tetrandrine as a drug are also considered.

Gamma sensitivity of forest plants of Western Ghats.

Seeds of Artocarpus hirsutus Lam., Garcinia xanthochymus Hook., Saraca asoca Roxb., Rourea minor Gaertn., Pterocarpus marsupium Roxb., Terminalia chebula Retz., Aporusa lindleyana (Wt.) bail., Holoptelea integrifolia Roxb. and Oroxylum indicum (L.) Vent. were collected from different regions of Western Ghats and exposed to different doses of gamma radiation using Co-60 source. The effect of irradiation was examined on germination, growth and vigor parameters. Decrease in the germination and growth attributes with increased dose was observed in A. hirsutus, G. xanthochymus and S. asoca and thus indicating sensitivity of these plants to radiation. In contrast, enhancement in the germination (percentage), vigor and generation of leaves was observed for P. marsupium, T. chebula, H. integrifolia and O. indicum. These plants were classified as radiation tolerant because of the ability of their seedlings to successfully establish under radiation stress. R. minor and A. lindleyana were able to maintain viability up to 100 Gy dose, however, any further increase in the dose found to have negative effect.

Larvicidal activities of Knema attenuata (Hook. f. & Thomson) Warb. (Myristicaceae) extracts against Aedes albopictus Skuse and Anopheles stephensi Liston.

In recent years, uses of environment friendly and biodegradable natural insecticides of plant origin have received renewed attention as agents for vector control. The present study was undertaken to investigate the effect of aril and kernel extracts of Knema attenuata (Hook. f. & Thomson) Warb. (Myristicaceae) on larvae of Aedes albopictus Skuse and Anopheles stephensi Liston under laboratory conditions. The aril was extracted with chloroform and ethanol; the kernel was extracted with ethanol and hexane. The extracts were tested against the 3rd-4th instar larvae collected from Bunder area, Mangalore, India, which is a well-known fishing harbour, where several mosquito-borne diseases were reported. All the graded concentrations (100, 200, 300, 400 and 500 ppm) showed significant larval mortality after 24 h of observation. Chloroform extracts of aril showed 100% mortality against both larval forms of A. albopictus and A. stephensi at the concentration of 500 ppm. Among the extracts tested, chloroform extracts of aril and ethanol extracts of kernel exhibited higher toxicity against both A. albopictus (LC(50), 141 ppm and 159 ppm; LC(90), 290 ppm and 342 ppm) and A. stephensi (LC(50), 160 ppm and 162 ppm; LC90, 445 ppm and 458 ppm). Hexane extracts of kernel exhibited least toxicity against A. albopictus (LC50, 239 ppm; LC(90), 484 ppm), whereas ethanol extracts of aril showed the least toxicity against A. stephensi (LC(50), 290; LC(90), 498). A preliminary phytochemical assay revealed the presence of phenolics, tannins, steroids, terpenes, resins, and glycolipids in all the extracts. Alkaloids, flavonoids and saponins were absent. The lower LC(50) value of the chloroform extracts of K. attenuata aril indicates its potentiality as a larvicide against A. albopictus and A. stephensi mosquito larvae.

Medical ethnobotany of the Siddis of Uttara Kannada district, Karnataka, India.

A total of 98 medicinal preparations, involving 69 species of plants, used by the Siddis of Uttara Kannada in the state of Karnataka is described in this paper based on an ethnomedical field study. The finding includes 40 hitherto unknown medicinal uses of known medicinal plants. Among these, the use of the stem sap of Calamus thwaitesii as an antifertility drug, and the use of the flowers of Ichnocarpus frutescens and the rhizome of Hedychium coronarium in the treatment of diabetes are noteworthy. The knowledge of medicinal plants of the Siddis is distinct from that of another tribe of the same locality, the Gowlis.

Production of extracellular cellulase by Lunulospora curvula and Flagellospora penicillioides.

Studies on the production of extracellular cellulase in two aquatic hyphomycetes Lunulospora curvula and Flagellospora penicillioides have shown that several factors such as carbon source, nitrogen source, pH and temperature affect the production of the enzyme. Experiments have shown that carboxymethyl cellulose is the best source of carbon, and ammonium sulfate is the best source of nitrogen for the production of the enzyme. An optimum pH of 5.2 and a temperature of 28 degrees C was found to favor maximum enzyme activity in 12-d-old cultures. Glucose and sucrose were found to suppress the activity of the enzyme in both organisms.

Effect of pesticides on the growth of aquatic hyphomycetes.

The effect of two herbicides (paraquat and 2,4-dichlorophenoxybutyric acid) and two fungicides (mancozeb and captafol) was studied on the growth of Flagellospora penicillioides, Lunulospora curvula and Phalangispora constricta using the poisoned-food technique. The pesticides did not produce any inhibition of growth at concentrations up to 5 mg/l. The required concentration to bring about total inhibition of growth varied among the chemicals and the cultures. The herbicides produced a slight enhancement of culture growth at concentrations ranging from 1 to 25 mg/l.