rosin and Neoplasms

Cancer is a major cause of morbidity and mortality worldwide. Chemotherapeutic agents currently used in cancer treatment are associated with severe side effects and development of resistance. Thus, there is a pressing need for novel and more potent anticancer drugs with high selectivity for tumor cells and reduced toxicity to normal tissue. Natural products remain an important source of bioactive compounds and drug prototypes that can lead to new and more effective antitumor agents. Coniferous plants are rich in abietane diterpenoids with a wide range of biological activities that provide useful templates for synthetic modification. Abietic acid and dehydroabietic acid (DHA), the major diterpenic resin acids from Pinus rosin, and dehydroabietylamine found in commercial disproportionated rosin amine, display antibacterial and antitumor properties. These compounds and their synthetic derivatives have been reported as promising anticancer agents with potent growth inhibitory activity against several types of human cancer cell lines, including breast, ovarian, prostate, colon, liver, lung and cervical carcinoma cells. Their mechanisms of action are diverse and include DNA binding, induction of apoptosis or oncosis, tubulin polymerization inhibition and disruption of intracellular cholesterol transport. This review covers the main aspects of natural rosin abietane diterpenoids (abietic acid, DHA and DHAA) and synthetic derivatives concerning their anti-proliferative, cytotoxic and antitumor activities, mechanisms of action and structure- activity relationships relevant for the development of novel anticancer agents for cancer chemotherapy.

Topics: Abietanes; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Drug Development; Humans; Neoplasms; Resins, Plant; Structure-Activity Relationship

The paper presents a review of the scientific publications on Rhodiola rosea L. known for its adaptogenic characteristics. Biologically active substances salidroside, rosin, rosavin, rosarin and tyrosol, which are mainly found in plant rhizomes, demonstrate therapeutic effect. These active components effect the central nervous system by increasing the ability to concentrate, the mental and physical power; they are efficient in the asthenic states and improve general resistance of the cells and the organism against the harmful outer influence. They also prevent the heart system from stress and arrhythmias, and posses some antioxidant activity. Some data confirm that the Rhodiola rosea L. preparations stop the growth of the malignant tumors and metastases in the liver. Some preclinical and clinical data of the golden root preparations are discussed in the survey. The interaction of the herb with other medicines, its usage and effect, recommended doses, and its side effects are also reviewed in the paper.

Topics: Adaptation, Physiological; Adult; Animals; Anti-Arrhythmia Agents; Antidepressive Agents; Antineoplastic Agents; Antioxidants; Arrhythmias, Cardiac; Central Nervous System; Clinical Trials as Topic; Depression; Glucosides; Humans; Lymnaea; Medicine, Traditional; Mental Fatigue; Neoplasms; Phenols; Phenylethyl Alcohol; Phytotherapy; Plant Extracts; Plant Preparations; Rats; Resins, Plant; Rhodiola

Ceranib-2 is a recently discovered, poorly water-soluble potent ceramidase inhibitor, with the ability to suppress cancer cell proliferation and delay tumor growth. However, its poor water solubility and weak cellular bioavailability hinder its use as a therapeutic agent for cancer. PEGylated rosin esters are an excellent platform as a natural polymer for drug delivery applications, especially for controlling drug release due to their degradability, biocompatibility, capability to improve solubility, and pharmacokinetics of potent drugs. In this study, stable aqueous amphiphilic submicron-sized PEG400-rosin ester-ceranib-2 (PREC-2) particles, ranging between 100 and 350 nm in a 1:1 mixture, were successfully synthesized by solvent evaporation mediated by sonication.Conclusion: Stable aqueous PEGylated rosin ester nanocarriers might present a significant solution to improve solubility, pharmacokinetic, and bioavailability of ceranib-2, and hold promises for use as an anticancer adjacent drug after further investigations.

Topics: Antineoplastic Agents; Drug Carriers; HeLa Cells; Humans; Neoplasms; Polyethylene Glycols; Quinolones; Resins, Plant

A novel optically pure dinuclear copper(II) complex of a rosin derivative dehydroabietic acid (DHA, HL) was synthesized and fully characterized. The in vitro antitumor activities of the copper(II) complex Cu2(µ2-O)(L)4(DMF)2 (1) were explored and compared with those of a trinuclear iron(III) complex [Fe3(µ3-O)(L)6(CH3OH)2(CH3O)]·H2O (2). 1 was more cytotoxic than 2, and the in vitro cytotoxicity of 1 was comparable to that of cisplatin and oxaliplatin. The metal coordination improved the cytotoxicity of DHA. 1 could arrest cycle in G1 phase and induce apoptosis in MCF-7 cell. 1 increased reactive oxygen species level, GSSG/GSH ratio, and Ca2+ production, and caused the loss of mitochondrial membrane potential (Δψm) in MCF-7 cells. The up-regulated Bax and down-regulated Bcl-2 expression levels, caspase-9/caspase-3 activation, and the release of Cyt c demonstrate that 1 triggered mitochondria-mediated intrinsic apoptosis in MCF-7 cells. Caspase-8/caspase-4 activation and up-regulated Fas expression indicate that death receptor-mediated extrinsic apoptosis was included. Comet assay and up-regulated γ-H2AX and p53 expressions confirmed that 1 caused DNA damage in MCF-7 cells. Moreover, 1 led to enhancement of the biomarker of lipid peroxidation and the indicator of protein carbonylation in MCF-7 cells. All the results suggest that 1 could kill MCF-7 cells by generating oxidative stress, impairing DNA, promoting lipid peroxidation and protein carbonylation, and inducing apoptosis and autophagy. Furthermore, 1 also displayed antimetastatic activities with inhibition of cell invasion and migration, together with antiangiogenesis properties. On the whole, copper complex based on rosin derivatives is worth developing as metal-based antitumor drugs.

Topics: Abietanes; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Movement; Coordination Complexes; Copper; DNA Damage; Humans; Iron; Lipid Peroxidation; Membrane Potential, Mitochondrial; Mitochondria; Neoplasms; Oxidative Stress; Protein Carbonylation; Reactive Oxygen Species; Resins, Plant; Tumor Cells, Cultured; Wound Healing

Topics: Animals; Carcinogens; Coal Tar; Humans; Keratolytic Agents; Neoplasms; Resins, Plant