-
Molecules (Basel, Switzerland) Apr 2022The objectives of this study were to investigate the melanogenetic potential of the psoralen derivatives 5-hydroxypsoralen, 5-methoxypsoralen, 8-hydroxypsoralen,...
The objectives of this study were to investigate the melanogenetic potential of the psoralen derivatives 5-hydroxypsoralen, 5-methoxypsoralen, 8-hydroxypsoralen, 8-methoxypsoralen, and 5,8-dimethoxypsoralen in B16F10 melanoma cells. The results indicated that melanin production is significantly stimulated in B16F10 melanoma cells with 5-methoxypsoralen, 8-methoxypsoralen, and 5,8-dimethoxypsoralen, especially for 5-methoxypsoralen (bergapten), as reported previously. In addition, Western blot results showed that the protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2) increase after bergapten treatment for the first time. The results also showed that bergapten promotes the phosphorylation of Akt at Ser 473 and glycogen synthase kinase-3β at Ser 9. Moreover, bergapten increased the content of β-catenin in the cell cytoplasm and nucleus by reducing the phosphorylated β-catenin (p-β-catenin) content. The results also indicated that bergapten regulates melanogenesis by upregulating the phosphorylation of p38 and JNK-mitogen-activated protein kinase. Taken together, these findings suggest that the regulation of melanogenesis by bergapten may be mediated by the β-catenin and MAPK signaling pathways and that bergapten might provide new insights into the pathogenesis of pigmented diseases.
Topics: 5-Methoxypsoralen; Animals; Cell Line, Tumor; Ficusin; Furocoumarins; Melanins; Melanoma; Melanoma, Experimental; Methoxsalen; Monophenol Monooxygenase; beta Catenin
PubMed: 35565964
DOI: 10.3390/molecules27092613 -
Oxidative Medicine and Cellular... 2022Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit... (Review)
Review
Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit juice. This compound presents antibacterial, anti-inflammatory, hypolipemic, and anticancer effects and is successfully used as a photosensitizing agent. The present review focuses on the research evidence related to the therapeutic properties of bergapten collected in recent years. Many preclinical and studies have been evidenced the therapeutic action of BP; however, few clinical trials have been carried out to evaluate its efficacy. These clinical trials with BP are mainly focused on patients suffering from skin disorders such as psoriasis or vitiligo. In these trials, the administration of BP (oral or topical) combined with UV irradiation induces relevant lesion clearance rates. In addition, beneficial effects of bergamot extract were also observed in patients with altered serum lipid profiles and in people with nonalcoholic fatty liver. On the contrary, there are no clinical trials that investigate the possible effects on cancer. Although the bioavailability of BP is lower than that of its 8-methoxypsoralen (8-MOP) isomer, it has fewer side effects allowing higher concentrations to be administered. In conclusion, although the use of BP has therapeutic applications on skin disorders as a sensitizing agent and as components of bergamot extract as hypolipemic therapy, more trials are necessary to define the doses and treatment guidelines and its usefulness against other pathologies such as cancer or bacterial infections.
Topics: 5-Methoxypsoralen; Humans; Methoxsalen; Oils, Volatile; Photosensitizing Agents; Plant Extracts; Ultraviolet Rays
PubMed: 35509838
DOI: 10.1155/2022/8615242 -
Cancer Medicine Nov 2022This trial explores SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) METHODS: Forty-nine... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This trial explores SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) METHODS: Forty-nine patients were randomized to daily 460 or 920 mg oral SM-88 with MPS (SM-88 Regimen). The primary endpoint was objective response rate (RECIST 1.1).
RESULTS
Thirty-seven patients completed ≥ one cycle of SM-88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality-of-life (QOL) was maintained and trended in favor of 920 mg. SM-88 Regimen was well tolerated; a single patient (1/49) had related grade 3 and 4 adverse events, which later resolved. In the intention-to-treat population of 49 patients, the median overall survival (mOS) was 3.4 months (95% CI: 2.7-4.9 months). Those treated in the second line had an mOS of 8.1 months and a median PFS of 3.8 months. Survival was higher for patients with stable versus progressive disease (any line; mOS: 10.6 months vs. 3.9 months; p = 0.01).
CONCLUSIONS
SM-88 Regimen has a favorable safety profile with encouraging QOL effects, disease control, and survival trends. This regimen should be explored in the second-line treatment of patients with mPDAC.
CLINICALTRIALS
gov Identifier: NCT03512756.
Topics: Humans; Methoxsalen; Phenytoin; Antineoplastic Combined Chemotherapy Protocols; Sirolimus; Quality of Life; Pancreatic Neoplasms; Adenocarcinoma
PubMed: 35499204
DOI: 10.1002/cam4.4768 -
Molecules (Basel, Switzerland) Jan 2022L., an indigenous plant in Egypt, is widely used in traditional medicine due to its various pharmacological properties. We aimed to evaluate the anticancer properties...
L., an indigenous plant in Egypt, is widely used in traditional medicine due to its various pharmacological properties. We aimed to evaluate the anticancer properties of fruit methanol extract (AME) against liver cancer and to elucidate the active compound(s) and their mechanisms of action. Three fractions from AME (Hexane, CHCl, and EtOAc) were tested for their anticancer activities against HepG2 cell line in vitro (cytotoxicity assay, cell cycle analysis, annexin V-FITC apoptosis assay, and autophagy efflux assay) and in silico (molecular docking). Among the AME fractions, CHCl fraction revealed the most potent cytotoxic activity. The structures of compounds isolated from the CHCl fraction were elucidated using H- and C-NMR and found that Compound (xanthotoxin) has the strongest cytotoxic activity against HepG2 cells (IC 6.9 ± 1.07 µg/mL). Treating HepG2 cells with 6.9 µg/mL of xanthotoxin induced significant changes in the DNA-cell cycle (increases in apoptotic pre-G1 and G2/M phases and a decrease in the S-phase). Xanthotoxin induced significant increase in Annexin-V-positive HepG2 cells both at the early and late stages of apoptosis, as well as a significant decrease in autophagic flux in cancer compared with control cells. In silico analysis of xanthotoxin against the DNA-relaxing enzyme topoisomease II (PDB code: 3QX3) revealed strong interaction with the key amino acid Asp479 in a similar fashion to that of the co-crystallized inhibitor (etoposide), implying that xanthotoxin has a potential of a broad-spectrum anticancer activity. Our results indicate that xanthotoxin exhibits anticancer effects with good biocompatibility toward normal human cells. Further studies are needed to optimize its antitumor efficacy, toxicity, solubility, and pharmacokinetics.
Topics: Ammi; Computer Simulation; Furocoumarins; In Vitro Techniques; Methoxsalen
PubMed: 35164207
DOI: 10.3390/molecules27030943 -
Transplantation and Cellular Therapy May 2022Therapy for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) involves intensive immunosuppression, which is associated with significant risk of infection....
Therapy for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) involves intensive immunosuppression, which is associated with significant risk of infection. Extracorporeal photopheresis (ECP) is used to treat SR-aGVHD and is considered more immunomodulatory than immunosuppressive. However, pediatric data are mostly retrospective and often involve multistep ECP that includes apheresis followed by separate photosensitizing/reinfusion on another device. This study aimed to prospectively evaluate the efficacy and safety of a single-device ECP system in children with SR-aGVHD. In this open-label multicenter phase 3 study of the Therakos CellEx Photopheresis System in children/young adults age 1 to 21 years with SR-aGVHD. Patients were treated 3 times per week for 4 weeks, then twice weekly through week 12 while maintaining standard aGVHD prophylaxis. The primary efficacy endpoint was the proportion of patients achieving an overall response (OR) at day +28 without the addition of next-line systemic treatment. Secondary endpoints included the proportion of patients achieving OR at weeks 8 and 12; the mean weekly steroid dose at weeks 4, 8, and 12; and treatment-emergent adverse events (TEAEs). Twenty-nine children (median age, 8 years) were enrolled. OR was 55% by day 28, 74% by week 8, and 79% by week 12. Progressive improvements were observed in the skin and the gastrointestinal tract. The mean steroid dose was decreased from 1.54 mg/kg/day at baseline to 0.90 mg/kg/day at week 4; 35% of patients achieved a >50% steroid dose reduction by week 4, and 75% achieved a >50% steroid dose reduction by week 12. Of the 168 TEAEs reported among 25 patients (86%), 28 events (17%) were infections and 14 events (8%) were considered likely treatment related (all nonserious). Of 627 ECP treatments administered in children and young adults, 68% required blood priming. TEAEs related to Uvadex or ECP were rare, hypocalcemia was the most common (3 events total). Three deaths occurred and were deemed unrelated to ECP by the investigators. Use of the Therakos CellEx Photopheresis System was effective in children with SR-aGVHD, with more than one-half experiencing improvement by day 28 and further responses observed over 12 weeks. Very few TEAEs were attributable to ECP, and no new safety signals were observed.
Topics: Adolescent; Adult; Child; Child, Preschool; Graft vs Host Disease; Humans; Infant; Photopheresis; Prospective Studies; Retrospective Studies; Steroids; Young Adult
PubMed: 35124293
DOI: 10.1016/j.jtct.2022.01.025 -
Frontiers in Chemistry 2021In this work, we synthesize the sulfonated Schiff bases of the chitosan derivatives 2a-2j without the use of a catalyst in two moderately straightforward steps with good...
In this work, we synthesize the sulfonated Schiff bases of the chitosan derivatives 2a-2j without the use of a catalyst in two moderately straightforward steps with good yield within a short reaction time. The morphology and chemical structure of chitosan derivatives were investigated using FT-IR, NMR (H-C), XRD, and SEM. Furthermore, our chitosan derivatives were tested for their anticancer activity against the MCF-7 cancer cell line, and doxorubicin was used as a standard. In addition, the normal cell lines of the breast cancer cell MCF-10A, and of the lung cell MRC-5 were tested. Compound 2 h, with a GI value of 0.02 µM for MCF-7, is highly active compared with the standard doxorubicin and other compounds. The synthesized compounds 2a-2j exhibit low cytotoxicity, with IC > 100 μg/ml, against normal cell lines MCF-10A, MRC-5. We also provide the results of an study involving the Methoxsalen protein (1Z11). Compound 2h exhibits a higher binding affinity for 1Z11 protein (-5.9 kcal/mol) and a lower binding affinity for Doxorubicin (-5.3 kcal/mol) than certain other compounds. As a result of the aforementioned findings, the use of compound 2h has an anticancer drug will be researched in the future.
PubMed: 35111729
DOI: 10.3389/fchem.2021.796599 -
International Journal of Molecular... Dec 2021Aqueous-ethanol extracts (70%) from the leaves of Regel. (Ranunculaceae Juss.)-collected from natural populations of Kyrgyzstan-were studied by liquid chromatography...
Aqueous-ethanol extracts (70%) from the leaves of Regel. (Ranunculaceae Juss.)-collected from natural populations of Kyrgyzstan-were studied by liquid chromatography with high-resolution mass spectrometry (LC-HRMS). There was no variation of the metabolic profiles among plants that were collected from different populations. More than 160 compounds were found in the leaves, of which 72 were identified to the class level and 58 to the individual-compound level. The class of flavonoids proved to be the most widely represented (19 compounds), including six aglycones [quercetin, kaempferol, aromadendrin, 6-methoxytaxifolin, phloretin, and (+)-catechin] and mono- and diglycosides (the other 13 compounds). In the analyzed samples of , 14 fatty acid-related compounds were identified, but coumarins and furochromones that were found in were the most interesting result; furochromones khelloside, khellin, visnagin, and cimifugin were found in for the first time. Coumarins 5,7-dihydroxy-4-methylcoumarin, scoparone, fraxetin, and luvangetin and furochromones methoxsalen, 5--methylvisammioside, and visamminol-3'-O-glucoside were detected for the first time in the genus Salisb. For all the above compounds, the structural formulas are given. Furthermore, detailed information (with structural formulas) is provided on the diversity of chromones and furochromones in other representatives of . The presence of chromones in plants of the genus confirms its closeness to the genus L. because chromones are synthesized by normal physiological processes only in these members of the Ranunculaceae family.
Topics: Chromatography, Liquid; Chromones; Coumarins; Mass Spectrometry; Phytochemicals; Ranunculaceae
PubMed: 35008829
DOI: 10.3390/ijms23010406 -
Biomedicine & Pharmacotherapy =... Feb 2022Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and... (Review)
Review
Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and unsatisfactory long-term treatment effect. Recent studies have shown that butyrylcholinesterase (BuChE) inhibitors or double acetyl and butyryl cholinesterase inhibitors have better curative effects on AD, and the side effects are lower than those of specific AChE inhibitors. Dual target cholinesterase inhibitors have become a new hotspot in the research of anti-AD drugs. Herein, the synthesis and bioactivities of BuChE inhibitors were reviewed.
Topics: Acridines; Alzheimer Disease; Butyrylcholinesterase; Cholinesterase Inhibitors; Humans; Methoxsalen; Structure-Activity Relationship
PubMed: 34953393
DOI: 10.1016/j.biopha.2021.112556 -
International Journal of Molecular... Nov 2021Cytochrome P450 2A13 is an omitted brother of CYP2A6 that has an important role in the drug metabolism of liver. Due to extrahepatic expression, it has gained less... (Review)
Review
Cytochrome P450 2A13 is an omitted brother of CYP2A6 that has an important role in the drug metabolism of liver. Due to extrahepatic expression, it has gained less attention than CYP2A6, despite the fact that it plays a significant role in toxicant-induced pulmonary lesions and, therefore, lung cancer. The purpose of this mini-review is to summarize the basic knowledge about this enzyme in relation to the substrates, inhibitors, genetic polymorphisms, and transcriptional regulation that are known so far (September 2021).
Topics: Animals; Aryl Hydrocarbon Hydroxylases; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Lung; Lung Neoplasms; Methoxsalen; Polymorphism, Genetic; Substrate Specificity
PubMed: 34830188
DOI: 10.3390/ijms222212306 -
Acta Dermatovenerologica Alpina,... Jun 2021Hypopigmented mycosis fungoides (HMF) is a rare variant of patch stage MF, which is often misdiagnosed. A 35-year-old male presented with non-pruritic white patches on...
Hypopigmented mycosis fungoides (HMF) is a rare variant of patch stage MF, which is often misdiagnosed. A 35-year-old male presented with non-pruritic white patches on his chest that had been present for 10 years. The patient had previously been treated for leprosy without any improvement. Physical examination showed well-defined multiple hypopigmented patches and macules on the chest, posterior trunk, and gluteus, with some lesions exhibiting anhidrosis and central erythema. The result of sensibility examination was unclear. Slit-skin-smear examination for acid-fast bacilli and anti-phenolic-glycolipid-1 examination were negative. Histopathological examination showed Pautrier microabscesses. The patient was diagnosed with HMF and was treated with 16 mg methylprednisolone b.i.d., topical application of desoximetasone, and 1% methoxsalen lotion followed by sun exposure. A significant improvement was observed during the following 6 months. This case shows that HMF needs to be considered in patients presenting with chronic unexplained hypopigmented patches to avoid unnecessary treatment and progression to more advanced stages.
Topics: Adrenal Cortex Hormones; Adult; Humans; Hypopigmentation; Leprosy; Male; Mycosis Fungoides; Skin Neoplasms
PubMed: 34169706
DOI: No ID Found