Mechanisms involved in the cytoprotective effects of Lonomia obliqua venom on human endometrial stromal cells.

The pathophysiology of recurrent pregnancy loss (RPL) involves deficiencies in the proliferation and migration capacities of endometrial stromal cells (hESCs), which impair embryo implantation and development. Since animal venoms are rich source of bioactive molecules, we aimed to characterize the cytoprotective effects of Lonomia obliqua venom on hESCs. hESCs were isolated from endometrial biopsies and the mechanisms of L. obliqua venomous secretions on cell viability, proliferation and migration were characterized. Venom components were identified by chromatography and proteomic analyses. L. obliqua venom induced hESC proliferation, viability and migration in a dose-dependent manner, both in the presence and absence of serum. By ion-exchange chromatography, one fraction enriched in cytoprotective components and devoid of hemotoxins was obtained. Venom proteome identified at least six protein classes with potential cytoprotective properties (hemolins, lipocalins, hemocyannins, antiviral proteins, antimicrobial peptides, and protease inhibitors). L. obliqua venom protected hESCs from oxidative insult. Cytoprotection was also related to nitric oxide and PKC-ERK-activation and down-regulation of cAMP-PKA-dependent pathways that control cell proliferation. L. obliqua venom-induced hESC viability, proliferation and migration occurs mainly by protecting against oxidative damage and activating ERK. Thus, L. obliqua venom components are promising pharmacological tools to understand the underlying mechanisms of hESC deficiency in RPL.

Oxidative stress promotes cytotoxicity in human cancer cell lines exposed to Escallonia spp. extracts.

BACKGROUND: Standard cancer treatments show a lack of selectivity that has led to the search for new strategies against cancer. The selective elimination of cancer cells modulating the redox environment, known as "selective oxycution", has emerged as a viable alternative. This research focuses on characterizing the unexplored Escallonia genus plant extracts and evaluating their potential effects on cancer's redox balance, cytotoxicity, and activation of death pathways. METHODS: 36 plant extracts were obtained from 4 different species of the Escallonia genus (E. illinita C. Presl, E. rubra (Ruiz & Pav.) Pers., E. revoluta (Ruiz & Pav.) Pers., and E. pulverulenta (Ruiz & Pav.) Pers.), which were posteriorly analyzed by their phytoconstituents, antioxidant capacity, and GC-MS. Further, redox balance assays (antioxidant enzymes, oxidative damage, and transcription factors) and cytotoxic effects (SRB, ∆Ψmt, and caspases actives) of those plant extracts were analyzed on four cell lines (HEK-293T, MCF-7, HT-29, and PC-3). RESULTS: 36 plant extracts were obtained, and their phytoconstituents and antioxidant capacity were established. Further, only six extracts had EC50 values < 10 µg*mL- 1, indicating high toxicity against the tested cells. From those, two plant extracts were selective against different cancer cell lines: the hexane extract of E. pulverulenta´s stem was selective for HT-29, and the ethyl acetate extract of E. rubra´s stem was selective for PC-3. Both extracts showed unbalanced redox effects and promoted selective cell death. CONCLUSIONS: This is the first study proving "selective oxycution" induced by Chilean native plant extracts.

Effect of Electrical Stimulation on PC12 Cells Cultured in Different Hydrogels: Basis for the Development of Biomaterials in Peripheral Nerve Tissue Engineering.

Extensive damage to peripheral nerves is a health problem with few therapeutic alternatives. In this context, the development of tissue engineering seeks to obtain materials that can help recreate environments conducive to cellular development and functional repair of peripheral nerves. Different hydrogels have been studied and presented as alternatives for future treatments to emulate the morphological characteristics of nerves. Along with this, other research proposes the need to incorporate electrical stimuli into treatments as agents that promote cell growth and differentiation; however, no precedent correlates the simultaneous effects of the types of hydrogel and electrical stimuli. This research evaluates the neural differentiation of PC12 cells, relating the effect of collagen, alginate, GelMA, and PEGDA hydrogels with electrical stimulation modulated in four different ways. Our results show significant correlations for different cultivation conditions. Electrical stimuli significantly increase neural differentiation for specific experimental conditions dependent on electrical frequency, not voltage. These backgrounds allow new material treatment schemes to be formulated through electrical stimulation in peripheral nerve tissue engineering.

Cytotoxic Activity, Topoisomerase I Inhibition and In Silico Studies of New Sesquiterpene-aryl Ester Derivatives of (-) Drimenol.

In this study, we aimed to evaluate two sets of sesquiterpene-aryl derivatives linked by an ester bond, their cytotoxic activities, and their capacity to activate caspases 3/7 and inhibit human topoisomerase I (TOP1). A total of 13 compounds were synthesized from the natural sesquiterpene (-)-drimenol and their cytotoxic activity was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and an immortalized non-tumoral cell line (MCF-10). From the results, it was observed that 6a was the most promising compound due to its cytotoxic effect on three cancer cell lines and its selectivity, 6a was 100-fold more selective than 5-FU in MCF-7 and 20-fold in PC-3. It was observed that 6a also induced apoptosis by caspases 3/7 activity using a Capsase-Glo-3/7 assay kit and inhibited TOP1. A possible binding mode of 6a in a complex with TOP1-DNA was proposed by docking and molecular dynamics studies. In addition, 6a was predicted to have a good pharmacokinetic profile for oral administration. Therefore, through this study, it was demonstrated that the drimane scaffold should be considered in the search of new antitumoral agents.

Rootstock increases the physiological defence of tomato plants against Pseudomonas syringae pv. tomato infection.

Climate change has intensified the infection of tomato plants by pathogens such as Pseudomonas syringae pv. tomato (Pst). Rootstocks may increase plant tolerance to leaf phytopathogens. The aim of this study was to evaluate the effects of the tolerant Poncho Negro (R) tomato rootstock on physiological defence and the role of hydrogen sulfide (H2S) in susceptible Limachino (L) tomato plant responses to Pst attack. Ungrafted (L), self-grafted (L/L), and grafted (L/R) plants were infected with Pst. Rootstock increased the concentration of antioxidant compounds including ascorbate in the scion. Tolerant rootstock induced an increase of H2S in the scion, which correlated with enhanced expression of the SlAPX2 gene. A high accumulation of salicylic acid was observed in Pst-inoculated grafted L/L and L/R plants, but this was higher in L/R plants. The increase of H2S during Pst infection was associated with a reduction of ethylene in L/R plants. Our study indicates that the Poncho Negro rootstock reduced the symptoms of bacterial speck disease in the Limachino tomato plants, conferring tolerance to Pst infection. This study provides new knowledge about the impact of rootstock in the defence of tomato plants against leaf pathogens that could be used in sustainable management of tomato cultivation.

Antitumoral Activity of Leptocarpha rivularis Flower Extracts against Gastric Cancer Cells.

Leptocarpha rivularis is a native South American plant used ancestrally by Mapuche people to treat gastrointestinal ailments. L. rivularis flower extracts are rich in molecules with therapeutic potential, including the sesquiterpene lactone leptocarpin, which displays cytotoxic effects against various cancer types in vitro. However, the combination of active molecules in these extracts could offer a hitherto unexplored potential for targeting cancer. In this study, we investigated the effect of L. rivularis flower extracts on the proliferation, survival, and spread parameters of gastric cancer cells in vitro. Gastric cancer (AGS and MKN-45) and normal immortalized (GES-1) cell lines were treated with different concentrations of L. rivularis flower extracts (DCM, Hex, EtOAc, and EtOH) and we determined the changes in proliferation (MTS assay, cell cycle analysis), cell viability/cytotoxicity (trypan blue exclusion assay, DEVDase activity, mitochondrial membrane potential MMP, and clonogenic ability), senescence (ß-galactosidase activity) and spread potential (invasion and migration assays using the Boyden chamber approach) in all these cells. The results showed that the DCM, EtOAc, and Hex extracts display a selective antitumoral effect in gastric cancer cells by affecting all the cancer parameters tested. These findings reveal an attractive antitumoral potential of L. rivularis flower extracts by targeting several acquired capabilities of cancer cells.

Estudio comparativo de la actividad anti-fúngica de extractos secuenciales de Fuchsia lycioides contra Candida sp / comparative study of the antifungal activity of sequencial extracts of Fuchsia lycioides against Candida sp

The genus Fuchsia is generally used in herbal preparations to treat conditions caused by microorganisms. Based on the popular use of this type of plants, the objective of this study was to obtain sequential extracts of increasing polarity from the branches of Fuchsia lycioides by maceration at room temperature and by the Soxhlet method at 60ºC, to later evaluate the antifungal capacity of the extracts against different clinical isolates of the Candida genus. The ethyl acetate extract exhibited strong anti-fungal activity, selectively inhibiting C. albicans strains with MIC and CMF values of 10 and 15 µg/mL, respectively; comparable with the drug itraconazole®. The analysis of the extract by GC-MS showed a high concentration of terpenoids (mainly phytol) and phenylpropanoids (mainly cinnamic acid), possibly responsible for the antifungal activity of the ethyl acetate extract of F. lycioides.

El género Fuchsia se usa generalmente en preparaciones de hierbas para tratar afecciones provocadas por microorganismos. En base al uso popular de este tipo de plantas, el objetivo de este estudio fue obtener los extractos secuenciales de polaridad creciente de las ramas de Fuchsia lycioides por maceración a temperatura ambiente y por el método Soxhlet a 60ºC, para luego evaluar la capacidad antifúngica de los extractos frente a diferentes aislados clínicos del genero Candida. El extracto de acetato de etilo exhibió una fuerte actividad antifúngica inhibiendo en forma selectiva las cepas de C. albicans con valores de CMI y de CMF de 10 y 15 µg/mL, respectivamente; comparables con el fármaco itraconazol®. El análisis del extracto por CG-EM mostró una alta concentración de terpenoides (principalmente fitol) y fenilpropanoides (principalmente ácido cinámico), posibles responsables de la actividad antifúngica del extracto de acetato de etilo de F. lycioides.

Chemical Analysis and In Vitro Bioactivity of Essential Oil of Laurelia sempervirens and Safrole Derivatives against Oomycete Fish Pathogens.

In this study, the essential oil (EO) from Laurelia sempervirens was analyzed by GC/MS and safrole (1) was identified as the major metabolite 1, was subjected to direct reactions on the oxygenated groups in the aromatic ring and in the side chain, and eight compounds (4 to 12) were obtained by the process. EO and compounds 4-12 were subjected to biological assays on 24 strains of the genus Saprolegnia, specifically of the species 12 S. parasitica and 12 S. australis. EO showed a significant effect against Saprolegnia strains. Compound 6 presents the highest activity against two resistant strains, with minimum inhibitory concentration (MIC) and minimum oomyceticidal concentration (MOC) values of 25 to 100 and 75 to 125 µg/mL, respectively. The results show that compound 6 exhibited superior activities compared to the commercial controls bronopol and azoxystrobin used to combat these pathogens.

Antifungal Nanoformulation for Biocontrol of Tomato Root and Crown Rot Caused by Fusarium oxysporum f. sp. radicis-lycopersici.

Tomatoes (Solanum lycopersicum L.) are the most cultivated and important vegetable crop in the world. These plants can wilt during crop growth due to fusarium wilt (fusariosis), a disease that damages tomato vascular systems. The Fusarium isolated and analyzed in this work correspond to Fusarium oxysporum f. sp. radicis-lycopersici. The isolates were molecularly identified, and analysis was done on the in vitro effects of the nanoemulsions (previously obtained from extracts of Chilean medicinal plants of the genera Psoralea and Escallonia) to inhibit mycelial and conidial germination of the isolates. Subsequently, the nanoemulsions were evaluated under greenhouse conditions for preventive control of fusariosis in the root and crown, with high levels of disease control observed using the highest concentrations of these nanoemulsions, at 250 and 500 ppm.

In Vitro Antifungal Activity and Toxicity of Dihydrocarvone-Hybrid Derivatives against Monilinia fructicola.

The aim of this study was to synthesize a series of novel and known dihydrocarvone-hybrid derivatives (2-9) and to evaluate mycelial growth activity of hybrid molecules against two strains of Monilinia fructicola, as well as their toxicity. Dihydrocarvone-hybrid derivatives have been synthesized under sonication conditions and characterized by FTIR, NMR, and HRMS. Antifungal efficacy against both strains of M. fructicola was determined by half maximal effective concentration (EC50) and toxicity using the brine shrimp lethality test (BSLT). Among the synthesized compounds, 7 and 8 showed the best activity against both strains of M. fructicola with EC50 values of 148.1 and 145.9 µg/mL for strain 1 and 18.1 and 15.7 µg/mL for strain 2, respectively, compared to BC 1000® (commercial organic fungicide) but lower than Mystic® 520 SC. However, these compounds showed low toxicity values, 910 and 890 µg/mL, respectively, compared to Mystic® 520 SC, which was highly toxic. Based on the results, these hybrid compounds could be considered for the development of more active, less toxic, and environmentally friendly antifungal agents against phytopathogenic fungi.

Analyses of Virulence Genes of Clavibacter michiganensis subsp. michiganensis Strains Reveal Heterogeneity and Deletions That Correlate with Pathogenicity.

Clavibacter michiganensis subsp. michiganensis (Cmm) is the causal agent of bacterial canker of tomato. Differences in virulence between Cmm strains have been reported. The aim of this study was the characterization of nine Cmm strains isolated in Chile to reveal the causes of their differences in virulence. The virulence assays in tomato seedlings revealed different levels of severity associated with the strains, with two highly virulent strains and one causing only mild symptoms. The two most virulent showed increased cellulase activity, and no cellulase activity was observed in the strain causing mild symptoms. In three strains, including the two most virulent strains, PCR amplification of the 10 virulence genes analyzed was observed. In the strain causing mild symptoms, no amplification was observed for five genes, including celA. Sequence and cluster analyses of six virulence genes grouped the strains, as has been previously reported, except for gene pelA1. Gene sequence analysis from the genomes of five Chilean strains revealed the presence of deletions in the virulence genes, celB, xysA, pat-1, and phpA. The results of this study allow us to establish correlations between the differences observed in disease severity and the presence/absence of genes and deletions not previously reported.

Volatile Organic Compounds (VOCs) Produced by Gluconobacter cerinus and Hanseniaspora osmophila Displaying Control Effect against Table Grape-Rot Pathogens.

Table grapes (Vitis vinifera) are affected by botrytis bunch rot and summer bunch rot, the latter a complex disease caused by Botrytis cinerea, Aspergillus spp., Penicillium expansum and Rhizopus stolonifer. To search for biocontrol alternatives, a new bioproduct composed of Gluconobacter cerinus and Hanseniaspora osmophila, a consortium called PUCV-VBL, was developed for the control of fungal rots in table grapes. Since this consortium presents new biocontrol species, the effect of their VOCs (volatile organic compounds) was evaluated under in vitro and in vivo conditions. The VOCs produced by the PUCV-VBL consortium showed the highest mycelial inhibition against Botrytis cinerea (86%). Furthermore, H. osmophila was able to inhibit sporulation of A. tubingensis and P. expansum. VOCs' effect in vivo was evaluated using berries from Red Globe, Thompson Seedless and Crimson Seedless grapes cultivars, demonstrating a mycelial inhibition by VOCs greater than 70% for all evaluated fungal species. The VOC identification of the PUCV-VBL consortium was analyzed by solid-phase microextraction coupled to gas chromatography-mass spectrometry (SPME-GCMS). A total 26 compounds were identified, including 1-butanol 3-methyl, propanoic acid ethyl ester, ethyl acetate, phenylethyl alcohol, isobutyl acetate and hexanoic acid ethyl ester. Our results show that VOCs are an important mode of action of the PUCV-VBL biological consortium.

Diffusible Compounds Produced by Hanseniaspora osmophila and Gluconobacter cerinus Help to Control the Causal Agents of Gray Rot and Summer Bunch Rot of Table Grapes.

Gray and summer bunch rot are important diseases of table grapes due to the high economic and environmental cost of their control with synthetic fungicides. The ability to produce antifungal compounds against the causal agents Botrytis, Aspergillus, Penicillium, and Rhizopus of two microorganisms isolated from table grapes and identified as Hanseniaspora osmophila and Gluconobacter cerinus was evaluated. In dual cultures, both biocontrol agents (together and separately) inhibited in vitro mycelial growth of these pathogens. To identify the compounds responsible for the inhibitory effect, extractions were carried out with organic solvents from biocontrol agents separately. Through dual cultures with pathogens and pure extracts, only the hexane extract from H. osmophila showed an inhibitory effect against Botrytis cinerea. To further identify these compounds, the direct bioautography technique was used. This technique made it possible to determine the band displaying antifungal activity at Rf = 0.05-0.2. The compounds present in this band were identified by GC-MS and compared to the NIST library. The most abundant compounds, not previously reported, corresponded to alkanes, ketones, alcohols, and terpenoids. H. osmophila and G. cerinus have the potential to control the causal agents of gray and summer bunch rot of table grapes.

Ultrasound assisted synthesis and cytotoxicity evaluation of known 2',4'-dihydroxychalcone derivatives against cancer cell lines.

This work reports on the development of an efficient and ecofriendly ultrasound assisted method for the high yield synthesis (70.0-94.0%) of eighteen oxyalkylated derivatives of 2',4'-dihydroxychalcone. Synthesized compounds were subjected to in vitro biological assays against HT-29 (colorectal), MCF-7 (breast), and PC-3 (prostate) human tumor cell lines, these cell lines are among the ten most aggressive malignancies diagnosed in the world. Cytotoxicity evaluations showed that four of the synthesized compounds exhibited moderate to very high toxic activity against MCF-7 (IC50 = 8.4-34.3 µM) and PC-3 (IC50 = 9.3-29.4 µM) - comparable to 5-fluorouracil (IC50 16.4-22.3 µM). The same compounds only showed moderate activity against HT-29 (IC50 15.3-36.3 µM), closer to daunorubicin (IC50 15.1 µM). Next, although selectivity index (SI) of compounds was weak, compound 18 exhibited a remarkable and selective cytotoxic activity (5.8-10.57) against cancer cells. Outside of these, most compounds significantly reduced cell survival, increased reactive oxygen species (ROS) and caspase activity, and decreased mitochondrial membrane permeability. In this sense, a portion of anti-proliferative activity is due to apoptosis. Notwithstanding, due to its remarkable response, chalcone 18 may be a potential alternative as a chemotherapeutic anti-carcinogen.

Activity of Adesmia boronioides resinous exudate against phytopathogenic bacteria.

Resinous exudate obtained from the aerial parts of Adesmia boronioides Hook.f. were evaluated to determine anti-phytopathogenic effects. Briefly, resinous exudate was obtained by dipping fresh plant material in dichloromethane; chemical composition was determined by GC-MS; and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated against four phytopathogenic bacteria. Resinous exudate yield was 8.5% (resin/fresh plant), of which esquel-6-en-9-one (14.25%), esquel-7-en-9-one (5.86%), and veratric acid (2.59%) were the effective antibacterial compounds. Tested against Pectobacterium carotovorum subsp. carotovora, Erwinia amylovora, Bacillus subtilis, and Pseudomonas syringae, MICs and MBCs ranged from 16 to 128 µg/mL and 32-256 µg/mL, respectively. These results provide initial evidence that resinous bush A. boronioides is a new and alternative source of substances with agricultural interest.

Use of clomiphene citrate protocol for controlled ovarian stimulation impairs endometrial maturity.

INTRODUCTION: Despite recent advances in assisted reproduction techniques and recent knowledge regarding embryo and endometrium quality, implantation and birth rates remain low. The objective of this study was to investigate whether clomiphene citrate alters endometrial maturation in infertile patients. METHODS: In a prospective self-matched cohort study, we assessed the ovulation of women in spontaneous and stimulated cycles (with clomiphene citrate). We determined the ovulation day by ultrasound scanning. In both cycles, we took four blood samples (BS1 - at early proliferative phase, BS2 - at mid proliferative phase, BS3 - after ovulation and BS4 - at mid luteal phase) to determine the serum concentrations of FSH, LH, estradiol and progesterone. We retrieved an endometrial biopsy five days after ovulation, followed by blinded analysis and classification according to Noyes criteria, in both cycles. RESULTS: Twenty-two participants completed the study. There were significant differences in FSH BS3 (p=0.001), in LH BS3 and BS4 (p<0.001 and p=0.049, respectively), in estradiol BS2, BS3 and BS4 (p<0.001, p=0.024 and p<0.001, respectively) and in progesterone BS3 and BS4 (p=0.028 and p<0.001, respectively). Considering Noyes criteria, there was a one-day delay when comparing the stimulated cycle with the spontaneous cycle (p=0.004), and a two-day delay when comparing the stimulated cycle with the biopsy day. CONCLUSION: This study indicates that ovarian stimulation with clomiphene citrate delays the endometrial maturity, and could possibly impair the implantation process due to asynchrony.

Chemical Composition, Antioxidant and Anticancer Activities of Leptocarpha rivularis DC Flower Extracts.

An evaluation of antioxidant and anticancer activity was screened in Leptocarpha rivularis DC flower extracts using four solvents (n-hexane (Hex), dichloromethane (DCM), ethyl acetate (AcOEt), and ethanol (EtOH)). Extracts were compared for total extract flavonoids and phenol contents, antioxidant activity (2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), ferric reducing antioxidant potential (FRAP), total reactive antioxidant properties (TRAP) and oxygen radical absorbance capacity (ORAC)) across a determined value of reduced/oxidized glutathione (GSH/GSSG), and cell viability (the sulforhodamine B (SRB) assay). The most active extracts were analyzed by chromatographic analysis (GC/MS) and tested for apoptotic pathways. Extracts from Hex, DCM and AcOEt reduced cell viability, caused changes in cell morphology, affected mitochondrial membrane permeability, and induced caspase activation in tumor cell lines HT-29, PC-3, and MCF-7. These effects were generally less pronounced in the HEK-293 cell line (nontumor cells), indicating clear selectivity towards tumor cell lines. We attribute likely extract activity to the presence of sesquiterpene lactones, in combination with other components like steroids and flavonoids.

Sonochemical Synthesis of 2'-Hydroxy-Chalcone Derivatives with Potential Anti-Oomycete Activity.

This work reports on the synthesis of eight new 2'-hydroxy-chalcones with potential anti-phytopathogenic applications in agroindustry, among others, via Claisen-Schmidt condensation and ultrasound assisted reaction. Assays showed three chalcones with allyl moieties strongly inhibited growth of phytopathogenic oomycete Phytophthora infestans; moreover, compound 8a had a half maximal effective concentration (EC50) value (32.5 µg/mL) similar to that of metalaxyl (28.6 µg/mL). A software-aided quantitative structure-activity relationship (QSAR) analysis of the whole series suggests that the structural features of these new chalcones-namely, the fluoride, hydroxyl, and amine groups over the carbon 3' of the chalcone skeleton-increase anti-oomycete activity.

Synthesis and Anti-Saprolegnia Activity of New 2',4'-Dihydroxydihydrochalcone Derivatives.

In the present study, seven 2',4'-dihydroxydihydrochalcone derivatives (compounds 3-9) were synthesized and their capacity as anti-Saprolegnia agents were evaluated against Saprolegnia parasitica, S. australis, S. diclina. Derivative 9 showed the best activity against the different strains, with minimum inhibitory concentration (MIC) and minimum oomyceticidal concentration (MOC) values between 100-175 µg/mL and 100-200 µg/mL, respectively, compared with bronopol and fluconazole as positive controls. In addition, compound 9 caused damage and disintegration cell membrane of all Saprolegnia strains over the action of commercial controls.

Antioxidant and Anti-Proliferative Activity of Essential Oil and Main Components from Leaves of Aloysia polystachya Harvested in Central Chile.

The aim of this study was to determine, first, the chemical composition of Aloysia polystachya (Griseb) Moldenke essential oil, from leaves harvested in central Chile; and second, its antioxidant and cytotoxic activity. Eight compounds were identified via gas chromatography-mass spectrometry (GC-MS) analyses, with the most representative being R-carvone (91.03%), R-limonene (4.10%), and dihydrocarvone (1.07%). For Aloysia polystachya essential oil, antioxidant assays (2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2, ferric reducing antioxidant power (FRAP), and total reactive antioxidant potential (TRAP)) showed good antioxidant activity compared to commercial antioxidant controls; and anti-proliferative assays against three human cancer cell lines (colon, HT-29; prostate, PC-3; and breast, MCF-7) determined an IC50 of 5.85, 6.74, and 9.53 µg/mL, and selectivity indices of 4.75, 4.12, and 2.92 for HT-29, PC-3, and MCF-7, respectively. We also report on assays with CCD 841 CoN (colon epithelial). Overall, results from this study may represent, in the near future, developments for natural-based cancer treatments.