Psychedelics: Alternative and Potential Therapeutic Options for Treating Mood and Anxiety Disorders.

The word "psychedelic" (psyche (i.e., the mind or soul) and delos (i.e., to show)) has Greek origin and was first coined by psychiatrist Humphry Osmond in 1956, who had been conducting research on lysergic acid diethylamide (LSD) at the time. Psychedelic drugs such as N,N-DMT/DMT (N,N-dimethyltryptamine), 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), LSD (lysergic acid diethylamide), MDMA (3,4-methylenedioxymethamphetamine) and psilocybin have had significant value as an entheogen in spiritual, religious (shamanic) and sociocultural rituals in Central and South American cultures for thousands of years. In the 1960s, the globalization of these drugs and their subsequent spread outside of their indigenous, old-world cultures, led to the subsequent implementation of strict drug control laws in many Western countries. Even today, psychedelics are still classified as Schedule I drugs, resulting in a still lingering negative stigmatization/perception, vilification, and ultimate criminalization of psychedelics. This controversy still lingers and still limits scientific research and full medical acceptance. For many years up until recently, the spiritual, religious and medicinal value of these drugs could not be explored in a scientific context. More recently, a second wave of psychedelic research is now focusing on psychedelics as neuropharmaceuticals to treat alcohol and tobacco addiction, general mood and anxiety disorders and cancer-related depression. There is now a vast array of promising evidence-based data to confirm the years of anecdotal evidence of the medicinal values of psychedelics. Natural therapeutic alternatives such as psychedelic drugs may provide a safe and efficacious alternate to conventional drugs used to treat mood and anxiety disorders. In a Western context in particular, psychedelic drugs as therapeutic agents for mood and anxiety disorders are becoming increasingly of interest amidst increasing rates of such disorders globally, changing social constructions, the implementation of government regulations and increasing investment opportunities, that ultimately allow for the scientific study to generate evidenced-based data. Alternative psychotherapeutic interventions are gaining interest also, because of their low physiological toxicity, relatively low abuse potential, safe psychological effects, and no associated persisting adverse physiological or psychological effects during and after use. On the other hand, conventional psychotic drugs and anti-depressants are becoming less favorable because of their adverse side effects. Psychedelic neuropharmaceutical interventions may with medical oversight be the solution to conventional psychiatric disorders such as depression and anxiety, and an alternative to conventional psychiatric treatment options. This paper will review the therapeutic potential of psychedelic drugs as alternative therapeutic options for mood and anxiety disorders in a controlled, clinical setting, where the chances of adverse psychological episodes occurring are mitigated.

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases.

The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as "C. sativa L." or "medical cannabis"), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.

Antiviral Activity of Jamaican Medicinal Plants and Isolated Bioactive Compounds.

Plants have had historical significance in medicine since the beginning of civilization. The oldest medical pharmacopeias of the African, Arabian, and Asian countries solely utilize plants and herbs to treat pain, oral diseases, skin diseases, microbial infections, multiple types of cancers, reproductive disorders among a myriad of other ailments. The World Health Organization (WHO) estimates that over 65% of the world population solely utilize botanical preparations as medicine. Due to the abundance of plants, plant-derived medicines are more readily accessible, affordable, convenient, and have safer side-effect profiles than synthetic drugs. Plant-based decoctions have been a significant part of Jamaican traditional folklore medicine. Jamaica is of particular interest because it has approximately 52% of the established medicinal plants that exist on earth. This makes the island particularly welcoming for rigorous scientific research on the medicinal value of plants and the development of phytomedicine thereof. Viral infections caused by the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), hepatitis virus B and C, influenza A virus, and the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) present a significant global burden. This is a review of some important Jamaican medicinal plants, with particular reference to their antiviral activity.

The Therapeutic Potential of Psilocybin.

The psychedelic effects of some plants and fungi have been known and deliberately exploited by humans for thousands of years. Fungi, particularly mushrooms, are the principal source of naturally occurring psychedelics. The mushroom extract, psilocybin has historically been used as a psychedelic agent for religious and spiritual ceremonies, as well as a therapeutic option for neuropsychiatric conditions. Psychedelic use was largely associated with the "hippie" counterculture movement, which, in turn, resulted in a growing, and still lingering, negative stigmatization for psychedelics. As a result, in 1970, the U.S. government rescheduled psychedelics as Schedule 1 drugs, ultimately ending scientific research on psychedelics. This prohibition on psychedelic drug research significantly delayed advances in medical knowledge on the therapeutic uses of agents such as psilocybin. A 2004 pilot study from the University of California, Los Angeles, exploring the potential of psilocybin treatment in patients with advanced-stage cancer managed to reignite interest and significantly renewed efforts in psilocybin research, heralding a new age in exploration for psychedelic therapy. Since then, significant advances have been made in characterizing the chemical properties of psilocybin as well as its therapeutic uses. This review will explore the potential of psilocybin in the treatment of neuropsychiatry-related conditions, examining recent advances as well as current research. This is not a systematic review.

Potential of Flavonoid-Inspired Phytomedicines against COVID-19.

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1ß, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiß as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.

HLBT-100: a highly potent anti-cancer flavanone from Tillandsia recurvata (L.) L.

BACKGROUND: The incidence and mortalities from cancers remain on the rise worldwide. Despite significant efforts to discover and develop novel anticancer agents, many cancers remain in the unmet need category. As such, efforts to discover and develop new and more effective and less toxic agents against cancer remain a top global priority. Our drug discovery approach is natural products based with a focus on plants. Tillandsia recurvata (L.) L. is one of the plants selected by our research team for further studies based on previous bioactivity findings on the anticancer activity of this plant. METHODS: The plant biomass was extracted using supercritical fluid extraction technology with CO2 as the mobile phase. Bioactivity guided isolation was achieved by use of chromatographic technics combined with anti-proliferative assays to determine the active fraction and subsequently the pure compound. Following in house screening, the identified molecule was submitted to the US National Cancer Institute for screening on the NCI60 cell line panel using standard protocols. Effect of HLBT-100 on apoptosis, caspase 3/7, cell cycle and DNA fragmentation were assessed using standard protocols. Antiangiogenic activity was carried out using the ex vivo rat aortic ring assay. RESULTS: A flavonoid of the flavanone class was isolated from T. recurvata (L.) L. with potent anticancer activity. The molecule was code named as HLBT-100 (also referred to as HLBT-001). The compound inhibited brain cancer (U87 MG), breast cancer (MDA-MB231), leukemia (MV4-11), melanoma (A375), and neuroblastoma (IMR-32) with IC50 concentrations of 0.054, 0.030, 0.024, 0.003 and 0.05 µM, respectively. The molecule also exhibited broad anticancer activity in the NCI60 panel inhibiting especially hematological, colon, CNS, melanoma, ovarian, breast and prostate cancers. Twenty-three of the NCI60 cell lines were inhibited with GI50 values <0.100 µM. In terms of potential mechanisms of action, the molecule demonstrated effect on the cell cycle as evidenced by the accumulation of cells with 

Exposure to Elevated Carbon Monoxide Levels at an Indoor Ice Arena--Wisconsin, 2014.

On December 13, 2014, the emergency management system in Lake Delton, Wisconsin, was notified when a male hockey player aged 20 years lost consciousness after participation in an indoor hockey tournament that included approximately 50 hockey players and 100 other attendees. Elevated levels of carbon monoxide (CO) (range = 45 ppm-165 ppm) were detected by the fire department inside the arena. The emergency management system encouraged all players and attendees to seek medical evaluation for possible CO poisoning. The Wisconsin Department of Health Services (WDHS) conducted an epidemiologic investigation to determine what caused the exposure and to recommend preventive strategies. Investigators abstracted medical records from area emergency departments (EDs) for patients who sought care for CO exposure during December 13-14, 2014, conducted a follow-up survey of ED patients approximately 2 months after the event, and conducted informant interviews. Ninety-two persons sought ED evaluation for possible CO exposure, all of whom were tested for CO poisoning. Seventy-four (80%) patients had blood carboxyhemoglobin (COHb) levels consistent with CO poisoning; 32 (43%) CO poisoning cases were among hockey players. On December 15, the CO emissions from the propane-fueled ice resurfacer were demonstrated to be 4.8% of total emissions when actively resurfacing and 2.3% when idling, both above the optimal range of 0.5%-1.0%. Incomplete fuel combustion by the ice resurfacer was the most likely source of elevated CO. CO poisonings in ice arenas can be prevented through regular maintenance of ice resurfacers, installation of CO detectors, and provision of adequate ventilation.

Cycloartane-3,24,25-triol inhibits MRCKα kinase and demonstrates promising anti prostate cancer activity in vitro.

BACKGROUND: Given the high occurrence of prostate cancer worldwide and one of the major sources of the discovery of new lead molecules being medicinal plants, this research undertook to investigate the possible anti-cancer activity of two natural cycloartanes; cycloartane-3,24,25-diol (extracted in our lab from Tillandsia recurvata) and cycloartane-3,24,25-triol (purchased). The inhibition of MRCKα kinase has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation. METHODS: Kinase inhibition was investigated using competition binding (to the ATP sites) assays which have been previously established and authenticated and cell proliferation was measured using the WST-1 assay. RESULTS: Cycloartane-3,24,25-triol demonstrated strong selectivity towards the MRCKα kinase with a Kd50 of 0.26 µM from a total of 451 kinases investigated. Cycloartane-3,24,25-triol reduced the viability of PC-3 and DU145 cell lines with IC50 values of 2.226 ± 0.28 µM and 1.67 ± 0.18 µM respectively. CONCLUSIONS: These results will prove useful in drug discovery as Cycloartane-3,24,25-triol has shown potential for development as an anti-cancer agent against prostate cancer.

Computerized physician order entry in the critical care environment: a review of current literature.

The implementation of health information technology (HIT) is accelerating, driven in part by a growing interest in computerized physician order entry (CPOE) as a tool for improving the quality and safety of patient care. Computerized physician order entry could have a substantial impact on patients in intensive care, where the potential for medical error is high, and the clinical workflow is complex. In 2009, only 17% of hospitals had functional CPOE systems in place. In intensive care unit (ICU) settings, CPOE has been shown to reduce the occurrence of some medication errors, but evidence of a beneficial effect on clinical outcomes remains limited. In some cases, new error types have arisen with the use of CPOE. Intensive care unit workflow and staff relationships have been affected by CPOE, often in unanticipated ways. The design of CPOE software has a strong impact on user acceptance. Intensive care unit-specific order sets lessen the cognitive workload associated with the use of CPOE and improve user acceptance. The diffusion of new technological innovations in the ICU can have unintended consequences, including changes in workflow, staff roles, and patient outcomes. When implementing CPOE in critical care areas, both organizational and technical factors should be considered. Further research is needed to inform the design and management of CPOE systems in the ICU and to better assess their impact on clinical end points, cost-effectiveness, and user satisfaction.

Non-Cannabinoid Metabolites of Cannabis sativa L. with Therapeutic Potential.

The cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most-prominent and most-studied secondary metabolites-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids-of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus OC43 (HCov-OC43) that is responsible for COVID-19, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.

The Current and Potential Application of Medicinal Cannabis Products in Dentistry.

Oral and dental diseases are a major global burden, the most common non-communicable diseases (NCDs), and may even affect an individual's general quality of life and health. The most prevalent dental and oral health conditions are tooth decay (otherwise referred to as dental caries/cavities), oral cancers, gingivitis, periodontitis, periodontal (gum) disease, Noma, oro-dental trauma, oral manifestations of HIV, sensitive teeth, cracked teeth, broken teeth, and congenital anomalies such as cleft lip and palate. Herbs have been utilized for hundreds of years in traditional Chinese, African and Indian medicine and even in some Western countries, for the treatment of oral and dental conditions including but not limited to dental caries, gingivitis and toothaches, dental pulpitis, halitosis (bad breath), mucositis, sore throat, oral wound infections, and periodontal abscesses. Herbs have also been used as plaque removers (chew sticks), antimicrobials, analgesics, anti-inflammatory agents, and antiseptics. Cannabis sativa L. in particular has been utilized in traditional Asian medicine for tooth-pain management, prevention of dental caries and reduction in gum inflammation. The distribution of cannabinoid (CB) receptors in the mouth suggest that the endocannabinoid system may be a target for the treatment of oral and dental diseases. Most recently, interest has been geared toward the use of Cannabidiol (CBD), one of several secondary metabolites produced by C. sativa L. CBD is a known anti-inflammatory, analgesic, anxiolytic, anti-microbial and anti-cancer agent, and as a result, may have therapeutic potential against conditions such burning mouth syndrome, dental anxiety, gingivitis, and possible oral cancer. Other major secondary metabolites of C. sativa L. such as terpenes and flavonoids also share anti-inflammatory, analgesic, anxiolytic and anti-microbial properties and may also have dental and oral applications. This review will investigate the potential of secondary metabolites of C. sativa L. in the treatment of dental and oral diseases.

Corrigendum: Flavonoid Derivative of Cannabis Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer.

[This corrects the article DOI: 10.3389/fonc.2019.00660.].

Flavonoid Derivative of Cannabis Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer.

Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%. One of the significant barriers to effective treatment is the immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed. This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer. In vitro results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy. Meanwhile, in vivo results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials. Repeated experiments also showed significant (P < 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts. The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.

A novel hybrid approach to automated negation detection in clinical radiology reports.

OBJECTIVE: Negation is common in clinical documents and is an important source of poor precision in automated indexing systems. Previous research has shown that negated terms may be difficult to identify if the words implying negations (negation signals) are more than a few words away from them. We describe a novel hybrid approach, combining regular expression matching with grammatical parsing, to address the above limitation in automatically detecting negations in clinical radiology reports. DESIGN: Negations are classified based upon the syntactical categories of negation signals, and negation patterns, using regular expression matching. Negated terms are then located in parse trees using corresponding negation grammar. MEASUREMENTS: A classification of negations and their corresponding syntactical and lexical patterns were developed through manual inspection of 30 radiology reports and validated on a set of 470 radiology reports. Another 120 radiology reports were randomly selected as the test set on which a modified Delphi design was used by four physicians to construct the gold standard. RESULTS: In the test set of 120 reports, there were a total of 2,976 noun phrases, of which 287 were correctly identified as negated (true positives), along with 23 undetected true negations (false negatives) and 4 mistaken negations (false positives). The hybrid approach identified negated phrases with sensitivity of 92.6% (95% CI 90.9-93.4%), positive predictive value of 98.6% (95% CI 96.9-99.4%), and specificity of 99.87% (95% CI 99.7-99.9%). CONCLUSION: This novel hybrid approach can accurately locate negated concepts in clinical radiology reports not only when in close proximity to, but also at a distance from, negation signals.

Potential of Cannabidiol for the Treatment of Viral Hepatitis.

Viral hepatitis B (HBV) and hepatitis C (HCV) pose a major health problem globally and if untreated, both viruses lead to severe liver damage resulting in liver cirrhosis and cancer. While HBV has a vaccine, HCV has none at the moment. The risk of drug resistance, combined with the high cost of current therapies, makes it a necessity for cost-effective therapeutics to be discovered and developed. The recent surge in interest in Medical Cannabis has led to interest in evaluating and validating the therapeutic potentials of Cannabis and its metabolites against various diseases including viruses. Preliminary screening of cannabidiol (CBD) revealed that CBD is active against HCV but not against HBV in vitro. CBD inhibited HCV replication by 86.4% at a single concentration of 10 µM with EC50 of 3.163 µM in a dose-response assay. These findings suggest that CBD could be further developed and used therapeutically against HCV. SUMMARY: Cannabidiol exhibited in vitro activity against viral hepatitis C. Abbreviations Used: CB2: Cannabis receptor 2, CBD: Cannabidiol, DNA: Deoxyribonucleic acid, HBV: Hepatitis B virus, HCV: Hepatitis C virus, HIV/AIDS: Human immunodeficiency virus/acquired immune deficiency syndrome, HSC: Hepatic stellate cells, MTS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, PCR: Polymerase chain reaction.

Improved identification of noun phrases in clinical radiology reports using a high-performance statistical natural language parser augmented with the UMLS specialist lexicon.

OBJECTIVE: The aim of this study was to develop and evaluate a method of extracting noun phrases with full phrase structures from a set of clinical radiology reports using natural language processing (NLP) and to investigate the effects of using the UMLS(R) Specialist Lexicon to improve noun phrase identification within clinical radiology documents. DESIGN: The noun phrase identification (NPI) module is composed of a sentence boundary detector, a statistical natural language parser trained on a nonmedical domain, and a noun phrase (NP) tagger. The NPI module processed a set of 100 XML-represented clinical radiology reports in Health Level 7 (HL7)(R) Clinical Document Architecture (CDA)-compatible format. Computed output was compared with manual markups made by four physicians and one author for maximal (longest) NP and those made by one author for base (simple) NP, respectively. An extended lexicon of biomedical terms was created from the UMLS Specialist Lexicon and used to improve NPI performance. RESULTS: The test set was 50 randomly selected reports. The sentence boundary detector achieved 99.0% precision and 98.6% recall. The overall maximal NPI precision and recall were 78.9% and 81.5% before using the UMLS Specialist Lexicon and 82.1% and 84.6% after. The overall base NPI precision and recall were 88.2% and 86.8% before using the UMLS Specialist Lexicon and 93.1% and 92.6% after, reducing false-positives by 31.1% and false-negatives by 34.3%. CONCLUSION: The sentence boundary detector performs excellently. After the adaptation using the UMLS Specialist Lexicon, the statistical parser's NPI performance on radiology reports increased to levels comparable to the parser's native performance in its newswire training domain and to that reported by other researchers in the general nonmedical domain.

Genomics in the clinic: ethical and policy challenges in clinical next-generation sequencing programs at early adopter USA institutions.

Next-generation sequencing (NGS) technologies are poised to revolutionize clinical diagnosis and treatment, but raise significant ethical and policy challenges. This review examines NGS program challenges through a synthesis of published literature, website and conference presentation content, and interviews at early-adopting institutions in the USA. Institutions are proactively addressing policy challenges related to the management and technical aspects of program development. However, ethical challenges related to patient-related aspects have not been fully addressed. These complex challenges present opportunities to develop comprehensive and standardized regulations across programs. Understanding the strengths, weaknesses and current practices of evolving NGS program approaches are important considerations for institutions developing NGS services, policymakers regulating or funding NGS programs and physicians and patients considering NGS services.

A pilot study of contextual UMLS indexing to improve the precision of concept-based representation in XML-structured clinical radiology reports.

OBJECTIVE: Despite the advantages of structured data entry, much of the patient record is still stored as unstructured or semistructured narrative text. The issue of representing clinical document content remains problematic. The authors' prior work using an automated UMLS document indexing system has been encouraging but has been affected by the generally low indexing precision of such systems. In an effort to improve precision, the authors have developed a context-sensitive document indexing model to calculate the optimal subset of UMLS source vocabularies used to index each document section. This pilot study was performed to evaluate the utility of this indexing approach on a set of clinical radiology reports. DESIGN: A set of clinical radiology reports that had been indexed manually using UMLS concept descriptors was indexed automatically by the SAPHIRE indexing engine. Using the data generated by this process the authors developed a system that simulated indexing, at the document section level, of the same document set using many permutations of a subset of the UMLS constituent vocabularies. MEASUREMENTS: The precision and recall scores generated by simulated indexing for each permutation of two or three UMLS constituent vocabularies were determined. RESULTS: While there was considerable variation in precision and recall values across the different subtypes of radiology reports, the overall effect of this indexing strategy using the best combination of two or three UMLS constituent vocabularies was an improvement in precision without significant impact of recall. CONCLUSION: In this pilot study a contextual indexing strategy improved overall precision in a set of clinical radiology reports.

Specific RSK kinase inhibition by dibenzyl trisulfide and implication for therapeutic treatment of cancer.

BACKGROUND/AIM: The Jamaican "Guinea Hen Weed" (Petiveria alliacea L.) plant has been traditionally used in folklore medicine to treat a variety of diseases including cancer. In the present study we investigated on the therapeutic feasibility of dibenzyl trisulfide (DTS) (isolated from the Jamaican Guinea Hen Weed) as a potent small-molecule kinase inhibitor to treat cancer. MATERIALS AND METHODS: We investigated the inhibitory effects of DTS against a large panel of kinases using a well-established competitive binding assay. Cell proliferation data were obtained using the WST-1 colorimetric assay. RESULTS: DTS inhibited the activity of the C-terminal kinase domain of RSK1 (80% compared to control) with a Kd of 1.3 µM. Anti-proliferative effects of DTS were observed in small lung, pancreatic, breast, and prostate cancer cells with IC50 values ranging from 0.34-0.84 µM. CONCLUSION: We have identified DTS as a highly selective and isoform-specific RSK1 kinase inhibitor with broad cancer therapeutic potential.

Antileukemic activity of Tillandsia recurvata and some of its cycloartanes.

BACKGROUND: Approximately 250,000 deaths were caused by leukemia globally in 2012 and about 40%-50% of all leukemia diagnoses end-up in death. Medicinal plants are a rich source for the discovery of new drugs against leukemia and other types of cancers. To this end, we subjected the Jamaican ball moss (Tillandsia recurvata) and its cycloartanes, as well as some analogs, to in vitro screening against a number of leukemia cell lines. The WST-1 anti-proliferation assay was used to determine the anticancer activity of ball moss and two cycloartanes isolated from ball moss and four of their analogs against four leukemia cell lines (HL-60, K562, MOLM-14, monoMac6). Ball moss crude methanolic extract showed activity with a 50% inhibition concentration (IC50) value of 3.028 µg/ml against the Molm-14 cell line but was ineffective against HL-60 cells. The six cycloartanes tested demonstrated varying activity against the four leukemia cancer cell lines with IC50 values ranging from 1.83 µM to 18.3 µM. Five out of the six cycloartanes demonstrated activity, while one was inactive against all four cell lines. The preliminary activity demonstrated by the Jamaican ball moss and its cycloartanes against selected leukemia cell lines continues to throw light on the broad anticancer activity of ball moss. Further studies to evaluate the efficacy of these molecules in other leukemia cell lines are required in order to validate the activity of these molecules, as well as to determine their mechanisms of action and ascertain the activity in vivo in order to establish efficacy and safety profiles.