John Gallien  Bhairavi Srinageshwar  Kellie Gallo  Gretchen Holtgrefe  Sindhuja Koneru  Paulina Sequeiros Otero  Catalina Alvarez Bueno  Jamie Mosher  Alison Roh  D. Stave Kohtz  Douglas Swanson  Ajit Sharma  Gary Dunbar  Julien Rossignol 《Molecules (Basel, Switzerland)》2021,26(19)

Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state. Curcumin, a well-known anti-inflammatory antioxidant, is a potential candidate for treatment of GB. To facilitate efficient delivery of therapeutic doses of curcumin into cells, we encapsulated the drug in surface-modified polyamidoamine (PAMAM) dendrimers. We studied the in vitro effectiveness of a traditional PAMAM dendrimer (100% amine surface, G4 NH₂), surface-modified dendrimer (10% amine and 90% hydroxyl-G4 90/10-Cys), and curcumin (Cur)-encapsulated dendrimer (G4 90/10-Cys-Cur) on three species of glioblastoma cell lines: mouse-GL261, rat-F98, and human-U87. Using an MTT assay for cell viability, we found that G4 90/10-Cys-Cur reduced viability of all three glioblastoma cell lines compared to non-cancerous control cells. Under similar conditions, unencapsulated curcumin was not effective, while the non-modified dendrimer (G4 NH₂) caused significant death of both cancerous and normal cells. By harnessing and optimizing the components of PAMAM dendrimers, we are providing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma.  相似文献   

    

Idowu E. Fadayomi  Okiemute R. Johnson-Ajinwo  Elisabete Pires  James McCullagh  Tim D.W. Claridge  Nicholas R. Forsyth  Wen-Wu Li 《Molecules (Basel, Switzerland)》2021,26(19)

Objectives: The toxicity of chemotherapeutic anticancer drugs is a serious issue in clinics. Drug discovery from edible and medicinal plants represents a promising approach towards finding safer anticancer therapeutics. Justicia insularis T. Anderson (Acanthaceae) is an edible and medicinal plant in Nigeria. This study aims to discover cytotoxic compounds from this rarely explored J. insularis and investigate their underlying mechanism of action. Methods: The cytotoxicity of the plant extract was evaluated in human ovarian cancer cell lines and normal human ovarian surface epithelia (HOE) cells using a sulforhodamine B assay. Bioassay-guided isolation was carried out using column chromatography including HPLC, and the isolated natural products were characterized using GC-MS, LC-HRMS, and 1D/2D NMR techniques. Induction of apoptosis was evaluated using Caspase 3/7, 8, and 9, and Annexin V and PI based flow cytometry assays. SwissADME and SwissTargetPrediction web tools were used to predict the molecular properties and possible protein targets of identified active compounds. Key finding: The two cytotoxic compounds were identified as clerodane diterpenoids: 16(α/β)-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide (1) and 16-oxo-cleroda-3,13(14)E-dien-15-oic acid (2) from the Acanthaceous plant for the first time. Compound 1 was a very abundant compound (0.7% per dry weight of plant material) and was shown to be more potent than compound 2 with IC₅₀ values in the micromolar range against OVCAR-4 and OVCAR-8 cancer cells. Compounds 1 and 2 were less cytotoxic to HOE cell line. Both compounds induced apoptosis by increasing caspase 3/7 activities in a concentration dependent manner. Compound 1 further increased caspase 8 and 9 activities and apoptosis cell populations. Compounds 1 and 2 are both drug like, and compound 1 may target various proteins including a kinase. Conclusions: Clerodane diterpenoids (1 and 2) in J. insularis were identified as cytotoxic to ovarian cancer cells via the induction of apoptosis, providing an abundant and valuable source of hit compounds for the treatment of ovarian cancer.  相似文献   

    

Huihai Yang  Man-Kit Cheung  Grace Gar-Lee Yue  Ping-Chung Leung  Chun-Kwok Wong  Clara Bik-San Lau 《Molecules (Basel, Switzerland)》2021,26(19)

Herba Patriniae (HP) are medicinal plants commonly used in colorectal cancer (CRC) patients. In this study, network pharmacology was used to predict the active components and key signaling pathways of HP in CRC. Patrinia heterophylla, one type of HP, was chosen for validation of the network pharmacology analysis. The phytochemical profile of Patrinia heterophylla water extract (PHW) was determined by UHPLC-MS. MTT, RT-PCR, and Western blot assays were performed to evaluate the bioactivities of PHW in colon cancer cells. Results showed that 15 potentially active components of HP interacted with 28 putative targets of CRC in the compound–target network, of which asperglaucide had the highest degree. Furthermore, the ErbB signaling pathway was identified as the pathway mediated by HP with the most potential against CRC. Both RT-PCR and Western blot results showed that PHW significantly downregulated the mRNA and protein levels of EGFR, PI3K, and AKT in HCT116 cells. Asperglaucide, present in PHW, exhibited an anti-migratory effect in HCT116 cells, suggesting that it could be an active component of PHW in CRC treatment. In conclusion, this study has provided the first scientific evidence to support the use of PHW in CRC and paved the way for further research into the underlying mechanisms of PHW against CRC.  相似文献   

    

Andreas S. Kalogirou  Michael P. East  Tuomo Laitinen  Chad D. Torrice  Kaitlyn A. Maffuid  David H. Drewry  Panayiotis A. Koutentis  Gary L. Johnson  Daniel J. Crona  Christopher R. M. Asquith 《Molecules (Basel, Switzerland)》2021,26(19)

A focused series of substituted 4H-1,2,6-thiadiazin-4-ones was designed and synthesized to probe the anti-cancer properties of this scaffold. Insights from previous kinase inhibitor programs were used to carefully select several different substitution patterns. Compounds were tested on bladder, prostate, pancreatic, breast, chordoma, and lung cancer cell lines with an additional skin fibroblast cell line as a toxicity control. This resulted in the identification of several low single digit micro molar compounds with promising therapeutic windows, particularly for bladder and prostate cancer. A number of key structural features of the 4H-1,2,6-thiadiazin-4-one scaffold are discussed that show promising scope for future improvement.  相似文献   

    

Kuen-Jang Tsai  Hsin-Yi Tsai  Chin-Chuan Tsai  Tai-Yu Chen  Tsung-Hua Hsieh  Chun-Lin Chen  Lulekiwe Mbuyisa  Yaw-Bin Huang  Ming-Wei Lin 《Molecules (Basel, Switzerland)》2021,26(21)

  相似文献   

    

Daniel L. Farkas 《Molecules (Basel, Switzerland)》2021,26(21)

Light is a powerful investigational tool in biomedicine, at all levels of structural organization. Its multitude of features (intensity, wavelength, polarization, interference, coherence, timing, non-linear absorption, and even interactions with itself) able to create contrast, and thus images that detail the makeup and functioning of the living state can and should be combined for maximum effect, especially if one seeks simultaneously high spatiotemporal resolution and discrimination ability within a living organism. The resulting high relevance should be directed towards a better understanding, detection of abnormalities, and ultimately cogent, precise, and effective intervention. The new optical methods and their combinations needed to address modern surgery in the operating room of the future, and major diseases such as cancer and neurodegeneration are reviewed here, with emphasis on our own work and highlighting selected applications focusing on quantitation, early detection, treatment assessment, and clinical relevance, and more generally matching the quality of the optical detection approach to the complexity of the disease. This should provide guidance for future advanced theranostics, emphasizing a tighter coupling—spatially and temporally—between detection, diagnosis, and treatment, in the hope that technologic sophistication such as that of a Mars rover can be translationally deployed in the clinic, for saving and improving lives.  相似文献   

    

Vernica Ibez Gaspar  Jasmin McCaul  Hilary Cassidy  Craig Slattery  Tara McMorrow 《Molecules (Basel, Switzerland)》2021,26(20)

The natural compound curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma (RCC) cells when combined with TNF-related apoptosis-inducing ligand (TRAIL), a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, the therapeutic effects of curcumin are limited by its low bioavailability. Similar compounds to curcumin with higher bioavailability, such as demethoxycurcumin (DMC) and 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), can potentially have similar anticancer effects and show a similar synergy with TRAIL, thus reducing RCC viability. This study aims to show the effects of DMC and EF24 in combination with TRAIL at reducing ACHN cell viability and ACHN cell migration. It also shows the changes in death receptor 4 (DR4) expression after treatment with these compounds individually and in combination with TRAIL, which can play a role in their mechanism of action.  相似文献   

    

Choon Ping Tan  Laura Sinigaglia  Valentí Gomez  Joanna Nicholls  Nagy A. Habib 《Molecules (Basel, Switzerland)》2021,26(21)

  相似文献   

    

Laphatrada Yurasakpong  Chanin Nantasenamat  Saksit Nobsathian  Kulathida Chaithirayanon  Somjai Apisawetakan 《Molecules (Basel, Switzerland)》2021,26(21)

Betulinic acid (BA) is a pentacyclic triterpene usually isolated from botanical sources. Numerous studies have reported the inhibitory effect of BA against human colorectal cancer cells (CRC). However, its effect on the expression of the molecular chaperone HSPA is unclear. The aim of this research is to investigate the anti-cancer activities of BA purified from Piper retrofractum and study its effect on the expression of HSPA in colorectal cancer HCT116 and SW480 cells. The viability of both cancer cells was reduced after they were treated with an increasing dosage of BA. Flow cytometry assay revealed that levels of cell apoptosis significantly increased after incubation with BA in both cancer cells. Pro-apoptotic markers including Bax, cleaved-caspase-3 and cleaved-caspase-9 were increased while anti-apoptotic marker Bcl-2 was decreased after BA treatment. Western blot also showed that the expression of HSPA fluctuated upon BA treatment, whereby HSPA was increased at lower BA concentrations while at higher BA concentrations HSPA expression was decreased. Preliminary molecular docking assay showed that BA can bind to the nucleotide binding domain of the HSP70 at its ADP-bound state of the HSP70. Although further research is needed to comprehend the BA-HSPA interaction, our findings indicate that BA can be considered as potential candidate for the development of new treatment for colorectal cancer.  相似文献   

    

Klaudia Michalska  Agnieszka Galanty  Thanh Nguyen Le  Janusz Malarz  Nguyen Quoc Vuong  Van Cuong Pham  Anna Stojakowska 《Molecules (Basel, Switzerland)》2021,26(22)

Maesa membranacea A. DC. (Primulaceae) is a plant species that has been frequently used by practitioners of the traditional ethnobotany knowledge from northern and central Vietnam. However, the chemical constituents of the plant remained unknown until recently. Chromatographic separation of a chloroform-soluble fraction of extract from leaves of M. membranacea led to the isolation of two new polyesterified ursane triterpenes (1–2) and two known apocarotenoids: (+)-dehydrovomifoliol (3) and (+)-vomifoliol (4). The chemical structures of the undescribed triterpenoids were elucidated using 1D and 2D MNR and HRESIMS spectral data as 2α,6β,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20β-diol (1) and 2α,6β,22α-triacetoxy-urs-12-ene-3α,11α,20β-triol (2). The newly isolated triterpenoids were tested for their cytotoxic activity in vitro against two melanoma cell lines (HTB140 and A375), normal skin keratinocytes (HaCaT), two colon cancer cell lines (HT29 and Caco-2), two prostate cancer cell lines (DU145 and PC3) and normal prostate epithelial cells (PNT-2). Doxorubicin was used as a reference cytostatic drug. The 2α,6β,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20β-diol demonstrated cytotoxic activity against prostate cancer cell lines (Du145—IC₅₀ = 35.8 µg/mL, PC3—IC₅₀ = 41.6 µg/mL), and at a concentration of 100 µg/mL reduced viability of normal prostate epithelium (PNT-2) cells by 41%.  相似文献