Cancer patients' behaviors and attitudes toward natural health products.

BACKGROUND: Natural health products (NHPs), including vitamins, minerals, and herbal supplements, are the most common complementary and alternative medicine (CAM) among cancer patients. Our survey determined the attitudes and behaviors of cancer patients toward natural complementary therapies that should be considered to implement an integrative approach in the future. METHODS: Our survey was conducted in four hospitals in Belgium. Questionnaires were posted online from October 2020 to October 2021 for cancer patients. Descriptive statistics were used to analyze the data. A [Formula: see text] test was applied to study the type of NHP consumed according to diagnosis time. Fischer's exact test compared patients who had changed their consumption since diagnosis and those who had not. RESULTS: Out of 349 questionnaires collected, only 59 met all inclusion criteria. 83.1 % of the patients agreed that conventional medicine (CM) could benefit from complementary therapies, but they did not estimate (72.3 % of the patients) that those latter are more effective than conventional medicine. More than half of the patients used five or more NHPs. The most frequent NHPs consumed daily were vitamins (64.4 %), followed by other products (i.e., probiotics, gemmotherapy, birch sap and omega 3/6) (42.4 %) and herbs (40.7 %). Almost all patients started taking NHPs before their cancer diagnosis, but 72.7 % have changed their consumption significantly (p = 0.009) since their diagnosis. Boosting the immune system (79.7 %) and limiting conventional treatment side effects (76.9 %) were the most common reasons for NHPs' use. 74.4 % of the patients did not take complementary therapies to delay or avoid conventional treatment. CONCLUSIONS: The combination and high diversity of NHPs consumption highlight the importance of educating patients and healthcare providers (HCPs) about the risk of drug interactions associated with these natural products. Most cancer patients are more interested in using this non-mainstream medicine to complement their conventional treatment than as an alternative. Knowing the patients' reasons and understanding patients' attitudes toward NHPs will be essential for HCPs to address NHPs' use.

Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database.

Cancer patients could combine herbal treatments with their chemotherapy. We consulted VigiBase, a WHO database of individual case safety reports (ICSRs) which archives reports of suspected Adverse Drug Reactions (ADRs) when herbal products are used in conjunction with anti-cancer treatment. We focused on the possible interactions between antineoplastic (L01 ATC class) or hormone antagonists (L02B ATC class) with 10 commonly used herbs (pineapple, green tea, cannabis, black cohosh, turmeric, echinacea, St John's wort, milk thistle and ginger) to compare ADRs described in ICSRs with the literature. A total of 1057 ICSRs were extracted from the database but only 134 were complete enough (or did not concern too many therapeutic lines) to keep them for analysis. Finally, 51 rationalizable ICSRs could be explained, which led us to propose a pharmacokinetic or pharmacodynamic interaction mechanism. Reports concerned more frequently women and half of the rationalizable ICSRs involved Viscum album and Silybum marianum. 5% of the ADRs described could have been avoided if clinicians had had access to the published information. It is also important to note that in 8% of the cases, the ADRs observed were life threatening. Phytovigilance should thus be considered more by health care professionals to best treat cancer patients and for better integrative care.

In Vitro Antioxidant and Anticancer Properties of Various E. senegalensis Extracts.

Although Erythrina senegalensis is a plant widely used in traditional medicine in sub-Saharan Africa, its biological properties have been poorly investigated to date. We first characterized by conventional reactions the composition of several stem bark extracts and evaluated in acellular and cellular assays their pro- or antioxidant properties supported by their high phenolic and flavonoid content, particularly with the methanolic extract. The pro- or antioxidant effects observed did not correlate with their IC50 concentrations against five cancer cell lines determined by MTT assay. Indeed, the CH2Cl2 extract and its ethyl acetate (EtOAc) subfraction appeared more potent although they harbored lower pro- or antioxidant effects. Nevertheless, at equipotent concentration, both extracts induced ER- and mitochondria-derived vacuoles observed by fluorescent microscopy that further led to non-apoptotic cell death. LC coupled to high resolution MS investigations have been performed to identify chemical compounds of the extracts. These investigations highlighted the presence of compounds formerly isolated from E. senegalensis including senegalensein that could be retrieved only in the EtOAc subfraction but also thirteen other compounds, such as 16:3-Glc-stigmasterol and hexadecanoic acid, whose anticancer properties have been previously reported. Nineteen other compounds remain to be identified. In conclusion, E. senegalensis appeared rich in compounds with antioxidant and anticancer properties, supporting its use in traditional practice and its status as a species of interest for further investigations in anticancer drug research.

Priming of mesenchymal stem cells with a hydrosoluble form of curcumin allows keeping their mesenchymal properties for cell-based therapy development.

Mesenchymal stem cells are increasingly studied for their use as drug-carrier in addition to their intrinsic potential for regenerative medicine. They could be used to transport molecules with a poor bioavailability such as curcumin in order to improve their clinical usage. This natural polyphenol, well-known for its antioxidant and anti-inflammatory properties, has a poor solubility that limits its clinical potential. For this purpose, the use of NDS27, a curcumin salt complexed with hydroxypropyl-beta-cyclodextrin (HPßCD), displaying an increased solubility in aqueous solution, is preferred. This study aims to evaluate the uptake of NDS27 into skeletal muscle-derived mesenchymal stem cells (mdMSCs) and the effects of such uptake onto their mesenchymal properties. It appeared that the uptake of NDS27 into mdMSCs is concentration-dependent and not time-dependent. The use of a concentration of 7 µmol/L which does not affect the viability and proliferation also allows preservation of their adhesion, invasion and T cell immunomodulatory abilities.

Systematic Review of Potential Anticancerous Activities of Erythrina senegalensis DC (Fabaceae).

The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant Erythrina senegalensis, focusing on compounds harboring activities against cancer models detailed in depth herein at both in vitro and in vivo preclinical levels. The review was conducted through Pubmed and Google Scholar. Nineteen out of the forty-two secondary metabolites isolated to date from E. senegalensis displayed interesting in vitro and/or in vivo antitumor activities. They belonged to alkaloid (Erysodine), triterpenes (Erythrodiol, maniladiol, oleanolic acid), prenylated isoflavonoids (senegalensin, erysenegalensein E, erysenegalensein M, alpinumisoflavone, derrone, warangalone), flavonoids (erythrisenegalone, senegalensein, lupinifolin, carpachromene) and pterocarpans (erybraedine A, erybraedine C, phaseollin). Among the isoflavonoids called "erysenegalensein", only erysenealenseins E and M have been tested for their anticancerous properties and turned out to be cytotoxic. Although the stem bark is the most frequently used part of the plant, all pterocarpans were isolated from roots and all alkaloids from seeds. The mechanisms of action of its metabolites include apoptosis, pyroptosis, autophagy and mitophagy via the modulation of cytoplasmic proteins, miRNA and enzymes involved in critical pathways deregulated in cancer. Alpinumisoflavone and oleanolic acid were studied in a broad spectrum of cancer models both in vitro and in preclinical models in vivo with promising results. Other metabolites, including carpachromen, phaseollin, erybraedin A, erysenegalensein M and maniladiol need to be further investigated, as they display potent in vitro effects.

Active free secretory component and secretory IgA in human milk: do maternal vaccination, allergy, infection, mode of delivery, nutrition and active lifestyle change their concentrations?

BACKGROUND: Free secretory component (free SC) in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion, but its concentration in human milk is unknown. To evaluate the relationship between free SC and SIgA, the influence of maternal factors (vaccination during pregnancy, allergy, previous infections, nutrition, mode of delivery and active lifestyle) on the concentrations of those secretory immune components in human milk was investigated. METHODS: Concentration of active free SC and SIgA in 124 milk samples from 91 mothers were measured via ELISA. RESULTS: Free SC in milk from Tdap-vaccinated mothers was lower than the Tdap-flu-vaccinated, flu-vaccinated or Rhogam-vaccinated mothers. Free SC in mothers who had a cesarean delivery was higher than mothers who had a vaginal delivery. Free SC in the nonallergic group was higher than the allergic group. Free SC was higher in mothers who rarely/never eat junk food, than in mothers who always/frequently eat junk food. Free SC also was higher in the moderate exercise group (active lifestyle) compared with the group who rarely/never exercise (sedentary lifestyle). Free SC in human milk was not affected by previous maternal infection or probiotic supplementation whereas SIgA was not changed by all investigated maternal factors. CONCLUSION: This study suggests that active free SC is more impacted by maternal factors than active SIgA in human milk. IMPACT: Active free secretory component (free SC) is more impacted by maternal factors than active secretory IgA (SIgA) in human milk. Vaccination during pregnancy, allergy, nutrition, type of delivery and active lifestyle affect the secretion of free SC in human milk, but not SIgA secretion. Free SC in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion against pathogens and its active concentration in milk strongly varies between mothers, partially due to their specific maternal background.

Discovery of Novel Potent Reversible and Irreversible Myeloperoxidase Inhibitors Using Virtual Screening Procedure.

The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. However, evidence has emerged that MPO-derived oxidants contribute to propagation of inflammatory diseases. Because of the deleterious effects of circulating MPO, there is a great interest in the development of new efficient and specific inhibitors. Here, we have performed a novel virtual screening procedure, depending on ligand-based pharmacophore modeling followed by structure-based virtual screening. Starting from a set of 727842 compounds, 28 molecules were selected by this virtual method and tested on MPO in vitro. Twelve out of 28 compounds were found to have an IC50 less than 5 µM. The best inhibitors were 2-(7-methoxy-4-methylquinazolin-2-yl)guanidine (28) and (R)-2-(1-((2,3-dihydro-1H-imidazol-2-yl)methyl)pyrrolidin-3-yl)-5-fluoro-1H-benzo[d]imidazole (42) with IC50 values of 44 and 50 nM, respectively. Studies on the mechanism of inhibition suggest that 28 is the first potent mechanism-based inhibitor and inhibits irreversibly MPO at nanomolar concentration.

Investigation of the Lignan Content in Extracts from Linum, Callitris and Juniperus Species in Relation to Their In Vitro Antiproliferative Activities.

Podophyllotoxin, a lignan still extracted from the rhizomes of Podophyllum hexandrum (Berberidaceae), is the starting molecule for the semisynthesis of widely used anticancer drugs such as etoposide. However, this source is threatened by the over-collection of P. hexandrum. Plants belonging to the Linaceae and Cupressaceae families could be attractive alternative sources with species that contain the lignan podophyllotoxin or its precursors and derivatives. Wild flax species, such as Linum flavum, as well as some Juniperus and Callitris species were investigated for their lignan content, and the in vitro antiproliferative capacity of their extracts was assayed on four tumor cell lines. Some of the lignans were detected by LC-HRMS for the first time in these extracts.In addition, lignans purified from these plants and compounds semisynthesized from commercially available podophyllotoxin were tested in terms of their in vitro antiproliferative activity. The genus Juniperus was the most promising given its in vitro antiproliferative effects, which were also observed with extracts from L. flavum and Callitris species.The in vitro antiproliferative effect of the plant extracts studied here appears to correlate well with the contents of the aryltetralin lignan podophyllotoxin and its glycoside as well as with deoxypodophyllotoxin and 6-methoxypodophyllotoxin. The strongest correlation between the lignan content of the extracts and the antiproliferative activity was observed for 6-methoxypodophyllotoxin. Regarding the possibility of producing large renewable amounts of 6-methoxypodophyllotoxin, this molecule could be of interest to produce new anticancer drugs and to bypass the resistance mechanisms against podophyllotoxin-derived drugs.

5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells.

Plants of the Amaryllidaceae family produce a large variety of alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting proliferation of cancer cells resistant to various pro-apoptotic stimuli and representing tumors with dismal prognoses refractory to current chemotherapy, such as glioma, melanoma, non-small-cell lung, esophageal, head and neck cancers, among others. Using this discovery as a starting point and taking advantage of a concise biomimetic route to the crinine skeleton, a collection of crinine analogues were synthetically prepared and evaluated against cancer cells. The compounds exhibited single-digit micromolar activities and retained this activity in a variety of drug-resistant cancer cell cultures. This investigation resulted in the discovery of new bicyclic ring systems with significant potential in the development of effective clinical cancer drugs capable of overcoming cancer chemotherapy resistance.

Cytotoxic Activity of Lomatiol and 7-(3'-Hydroxymethyl-3'-methylallyloxy)coumarin.

7-(3'-Hydroxymethyl-3'-methylallyloxy)coumarin, bearing a 3'-hydroxy-3'-methylallyl group as the O-side chain, and lomatiol, a lapachol derivative sharing the same structural feature, were tested for their in vitro growth inhibitory activities on six cancer cell lines using the MTT colorimetric assay, along with the respective 3',3'-dimethylallyl derivatives and unprenylated products used for comparison. Data revealed that lomatiol displayed the strongest growth inhibitory activities in vitro although not as efficient as the parent compound lapachol. The oxidized O-prenylcoumarin recorded better growth inhibitory capacities than the prenylated and unprenylated parent products

Glanduliferins A and B, two new glucosylated steroids from Impatiens glandulifera, with in vitro growth inhibitory activity in human cancer cells.

Impatiens glandulifera has been imported from Himalaya in Europe and is considered as an invasive alien plant whose spreading arouses increasing interest among scientific literature. Via anti-cancer bioguiding, two new glucosylated steroids, named glanduliferins A and B, were isolated from the dried stem of I. glandulifera plants, together with the well-known α-spinasterol and 2-methoxy-1,4-naphthoquinone, which are also isolated from roots and leaves. They were characterized as 17-(2-hydroxy-2-pentamethylcyclopropyl-ethyl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopents[a]phenathren-3-O-(4-O-acetyl)-α-D-glucopyranoside and 17-(4-ethyl-1,5-dimethyl-hex-2-enyl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopents[a]phenathren-3-O-(6-O-acetyl)-ß-D-glucopyranoside using various NMR and HRESIMS techniques and chemical methods. In vitro determination of the growth inhibitory activity of the four isolated compounds using the MTT colorimetric assay revealed mean IC50 growth inhibitory value of ~30 µM for glanduliferin A while glanduliferin B and α-spinasterol were poorly active till 100 µM. 2-methoxy-1,4-naphthoquinone revealed to be active in the single micromolar digit range as previously described. Quantitative videomicroscopy analyses of the effects of glanduliferins A and B suggested cytostatic rather than cytotoxic activity in U373 glioblastoma (GBM) cells.

Natural and Synthetic Furanones with Anticancer Activity.

This paper describes the enantioselective synthesis of analogues of sapinofuranones A and B, namely 5-substitutes dihydro- and 5H-furan-ones, and their in vitro growth inhibitory activity against six cancer cell lines in comparison with fungal furanones such as diplofuranone A, diplobifuranylones A and B, as well as (S,S)-enantiomer of sapinofuranone B. The compounds under study displayed weak if any in vitro growth inhibitory activity against the analysed cancer cell lines. -However, it seems that among dihydro- and 5H-furan-ones bearing a 1-hydroxypentyl side chain, the stereochemistry of the furanone ring and that of hydroxylated methine could modify the in vitro growth activity of these compounds. The natural furanones that showed a different unsaturated chain at C-4 or rearranged into a dihydrofuran ring appeared to be inactive in terms of growth inhibitory activity, e.g. displaying growth inhibitory concentration at 50% (GIs) > 100 ptM in all six cancer cell lines analysed.

Jonquailine, a new pretazettine-type alkaloid isolated from Narcissus jonquilla quail, with activity against drug-resistant cancer.

A new alkaloid, belonging to the pretazettine group of Amaryllidaceae alkaloids, was isolated from dried bulbs of Narcissus jonquilla quail and named jonquailine. Its structure, including the absolute configuration, was elucidated using various NMR, ECD and ESI MS techniques. Initial biological evaluation revealed significant antiproliferative effects against glioblastoma, melanoma, uterine sarcoma and non-small-cell lung cancer cells displaying various forms of drug resistance, including resistance to apoptosis and multi-drug resistance. Jonquailine was also found to synergize with paclitaxel in its antiproliferative action against drug-resistant lung cancer cells. The results obtained compared with literature data also showed that the hydroxylation at C-8 is an important feature for the anticancer activity but this seems unaffected by the stereochemistry or the acetalization of the lactol.

Synthesis and anti-cancer activity of naturally occurring 2,5-diketopiperazines.

Three naturally occurring oxyprenylated diketopiperazines were synthesized and preliminarily tested as growth inhibitory agents in vitro against various cancer cell lines. The compounds were tested on six human cancer cell lines with different sensitivity to proapoptotic stimuli using the MTT colorimetric assay. The data revealed that of the chemicals under study only deoxymicelianamide (11) displayed the highest activity, recording mean IC50 growth inhibitory values ranging from 2 to 23 µM. A comparative study with the non-geranylated saturated derivative of (11) revealed the importance of the presence of the geranyloxy side chain and the exocyclic 2,5-DPK double bond moiety for the observed activity.

Growth inhibitory activity for cancer cell lines of lapachol and its natural and semi-synthetic derivatives.

A series of 17 selected natural and semisynthetic 1,4-naphthoquinones were synthesized, and their growth inhibitory activity was evaluated in vitro. The compounds were tested on six human cancer cell lines using the MTT colorimetric assay. The data revealed that of the chemicals under study only lapachol, its acetate and 3-geranyllawsone displayed the highest activity, recording mean IC50 values ranging from 15 to 22 µM.

Secondary metabolites from a culture of the fungus Neosartorya pseudofischeri and their in vitro cytostatic activity in human cancer cells.

Four known (1, 2, 3, and 6) and three new compounds including a 1,4-diacetyl-2,5-dibenzylpiperazine derivative (4), a quinazolinone-containing indole derivative (5), and a new ester of 2,4-dihydroxy-6-methylbenzoic acid (7) were isolated from the fungus Neosartorya pseudofischeri S. W. Peterson. Compound 2 displayed in vitro growth inhibitory activity that ranged between the activities of etoposide and carboplatin, chosen as reference compounds, in six distinct cancer cell lines. Compound 1 displayed less activity than 2. Computer-assisted phase-contrast microscopy-related analysis revealed that 2 displayed cytostatic, not cytotoxic, effects in human U373 glioblastoma and A549 non-small cell lung cancer apoptosis-resistant cells with marked inhibition of mitotic rates. Cancer cells in the remaining phases of the cell cycle were unchanged. Flow cytometry analysis further confirmed that 2 does not induce apoptotic features in U373 or A549 cancer cells. Thus, 2 represents a novel chemical scaffold from which derivatives for anticancer cytostatic compounds can be derived.

In vitro growth inhibitory effects of cytochalasins and derivatives in cancer cells.

The in vitro anticancer activity of eight natural cytochalasins and three hemisynthetic derivatives of cytochalasin B on six cancer cell lines was evaluated. The IC (50) in vitro growth inhibitory concentrations, as determined by an MTT colorimetric assay, ranged between 3 and 90 µM and did not relate to the intrinsic sensitivity of the cancer cell lines to proapoptotic stimuli. Structure activity relationship (SAR) analyses revealed that the presence of an unmodified hydroxyl group at C-7 of the perhydroisoinsolyl-1-one residue as well as the functionalities and the conformational freedom of the macrocycle are all important features for cytochalasin-mediated anticancer activities in vitro. Computer-assisted phase-contrast microscopy revealed two groups of cytochalasins, i.e., cytotoxic versus cytostatic ones. Our data open new possibilities for tuning cytochalasin targets and developing nontoxic, cytostatic cytochalasins to combat cancers associated with poor prognoses, such as those that display intrinsic resistance to proapoptotic stimuli.