Displaying publications 1 - 20 of 252 in total

  1. Heng WS, Kruyt FAE, Cheah SC
    Int J Mol Sci, 2021 May 27;22(11).
    PMID: 34071790 DOI: 10.3390/ijms22115697
    Lung cancer is still one of the deadliest cancers, with over two million incidences annually. Prevention is regarded as the most efficient way to reduce both the incidence and death figures. Nevertheless, treatment should still be improved, particularly in addressing therapeutic resistance due to cancer stem cells-the assumed drivers of tumor initiation and progression. Phytochemicals in plant-based diets are thought to contribute substantially to lung cancer prevention and may be efficacious for targeting lung cancer stem cells. In this review, we collect recent literature on lung homeostasis, carcinogenesis, and phytochemicals studied in lung cancers. We provide a comprehensive overview of how normal lung tissue operates and relate it with lung carcinogenesis to redefine better targets for lung cancer stem cells. Nine well-studied phytochemical compounds, namely curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, luteolin, sulforaphane, berberine, genistein, and capsaicin, are discussed in terms of their chemopreventive and anticancer mechanisms in lung cancer and potential use in the clinic. How the use of phytochemicals can be improved by structural manipulations, targeted delivery, concentration adjustments, and combinatorial treatments is also highlighted. We propose that lung carcinomas should be treated differently based on their respective cellular origins. Targeting quiescence-inducing, inflammation-dampening, or reactive oxygen species-balancing pathways appears particularly interesting.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  2. Sim YY, Nyam KL
    Food Chem, 2021 May 15;344:128582.
    PMID: 33199120 DOI: 10.1016/j.foodchem.2020.128582
    The electronic database was searched up to July 2020, using keywords, kenaf and roselle, chemical constituents of kenaf and roselle, therapeutic uses of kenaf and roselle. Journals, books and conference proceedings were also searched. Investigations of pharmacological activities of kenaf revealed that this edible plant exhibits a broad range of therapeutic potential including antioxidant, antimicrobial, antityrosinase, anticancer, antihyperlipidemia, antiulcer, anti-inflammatory, and hepatoprotective activities. Kenaf also showed versatile utility as a functional ingredient in food, folk medicine, and animal nutritions, as well as in nanotechnology processes. The exploitation of underexploited kenaf by-products can be a significant part of waste management from an economic and environmental point of view. In addition, kenaf showed comparable nutritional, phytochemical, and pharmacological properties with Hibiscus sabdariffa (Roselle). This review has important implications for further investigations and applications of kenaf in food and pharmaceuticals industry.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  3. Maher T, Ahmad Raus R, Daddiouaissa D, Ahmad F, Adzhar NS, Latif ES, et al.
    Molecules, 2021 May 07;26(9).
    PMID: 34066963 DOI: 10.3390/molecules26092741
    Leukemia is a leukocyte cancer that is characterized by anarchic growth of immature immune cells in the bone marrow, blood and spleen. There are many forms of leukemia, and the best course of therapy and the chance of a patient's survival depend on the type of leukemic disease. Different forms of drugs have been used to treat leukemia. Due to the adverse effects associated with such therapies and drug resistance, the search for safer and more effective drugs remains one of the most challenging areas of research. Thus, new therapeutic approaches are important to improving outcomes. Almost half of the drugs utilized nowadays in treating cancer are from natural products and their derivatives. Medicinal plants have proven to be an effective natural source of anti-leukemic drugs. The cytotoxicity and the mechanisms underlying the toxicity of these plants to leukemic cells and their isolated compounds were investigated. Effort has been made throughout this comprehensive review to highlight the recent developments and milestones achieved in leukemia therapies using plant-derived compounds and the crude extracts from various medicinal plants. Furthermore, the mechanisms of action of these plants are discussed.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  4. Phang CW, Abd Malek SN, Karsani SA
    Biomed Pharmacother, 2021 May;137:110846.
    PMID: 33761587 DOI: 10.1016/j.biopha.2020.110846
    Chalcones and their derivatives belong to the flavonoid family. They have been extensively studied for their anticancer properties and some have been approved for clinical use. In this study, the in vivo anti-tumor activity of flavokawain C (FKC), a naturally occurring chalcone found in Kava (Piper methysticum Forst) was evaluated in HCT 116 cells (colon carcinoma). We also attempted to identify potential biomarkers and/or molecular targets in serum with applicability in predicting treatment outcome. The anti-tumor effects and toxicity of FKC were assessed using the xenograft nude mice model. Cisplatin was used as positive control. The anti-proliferative and apoptotic activities were then evaluated in tumor tissues treated with FKC. Furthermore, two-dimensional electrophoresis (2-DE) followed by protein identification using MALDI-TOF/TOF-MS/MS was performed to compare the serum proteome profiles between healthy nude mice and nude mice bearing HCT 116 tumor treated with vehicle solution and FKC, respectively. Our results showed that FKC treatment significantly inhibited HCT 116 tumor growth. In vivo toxicity studies showed that administration of FKC did not cause damage to major organs and had no significant effect on body weight. FKC was found to induce apoptosis in tumor, and this was associated with increased expression of cleaved caspase-3 and decreased expression of Ki67 in tumor tissues. Our proteomic analysis identified five proteins that changed in abundance - Ig mu chain C region (secreted form), GRP78, hemopexin, kininogen-1 and apolipoprotein E. Overall, our findings demonstrated the potential of FKC as an anti-cancer agent for the treatment of colon carcinoma.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  5. Shu YH, Yuan HH, Xu MT, Hong YT, Gao CC, Wu ZP, et al.
    Acta Pharmacol Sin, 2021 May;42(5):780-790.
    PMID: 32814819 DOI: 10.1038/s41401-020-0492-5
    Guangsangon E (GSE) is a novel Diels-Alder adduct isolated from leaves of Morus alba L, a traditional Chinese medicine widely applied in respiratory diseases. It is reported that GSE has cytotoxic effect on cancer cells. In our research, we investigated its anticancer effect on respiratory cancer and revealed that GSE induces autophagy and apoptosis in lung and nasopharyngeal cancer cells. We first observed that GSE inhibits cell proliferation and induces apoptosis in A549 and CNE1 cells. Meanwhile, the upregulation of autophagosome marker LC3 and increased formation of GFP-LC3 puncta demonstrates the induction of autophagy in GSE-treated cells. Moreover, GSE increases the autophagy flux by enhancing lysosomal activity and the fusion of autophagosomes and lysosomes. Next, we investigated that endoplasmic reticulum (ER) stress is involved in autophagy induction by GSE. GSE activates the ER stress through reactive oxygen species (ROS) accumulation, which can be blocked by ROS scavenger NAC. Finally, inhibition of autophagy attenuates GSE-caused cell death, termed as "autophagy-mediated cell death." Taken together, we revealed the molecular mechanism of GSE against respiratory cancer, which demonstrates great potential of GSE in the treatment of representative cancer.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  6. Daddiouaissa D, Amid A, Abdullah Sani MS, Elnour AAM
    J Ethnopharmacol, 2021 Apr 24;270:113813.
    PMID: 33444719 DOI: 10.1016/j.jep.2021.113813
    ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants have been used by indigenous people across the world for centuries to help individuals preserve their wellbeing and cure diseases. Annona muricata L. (Graviola) which is belonging to the Annonaceae family has been traditionally used due to its medicinal abilities including antimicrobial, anti-inflammatory, antioxidant and cancer cell growth inhibition. Graviola is claimed to be a potential antitumor due to its selective cytotoxicity against several cancer cell lines. However, the metabolic mechanism information underlying the anticancer activity remains limited.

    AIM OF THE STUDY: This study aimed to investigate the effect of ionic liquid-Graviola fruit pulp extract (IL-GPE) on the metabolomics behavior of colon cancer (HT29) by using an untargeted GC-TOFMS-based metabolic profiling.

    MATERIALS AND METHODS: Multivariate data analysis was used to determine the metabolic profiling, and the ingenuity pathway analysis (IPA) was used to predict the altered canonical pathways after treating the HT29 cells with crude IL-GPE and Taxol (positive control).

    RESULTS: The principal components analysis (PCA) identified 44 metabolites with the most reliable factor loading, and the cluster analysis (CA) separated three groups of metabolites: metabolites specific to the non-treated HT29 cells, metabolites specific to the treated HT29 cells with the crude IL-GPE and metabolites specific to Taxol treatment. Pathway analysis of metabolomic profiles revealed an alteration of many metabolic pathways, including amino acid metabolism, aerobic glycolysis, urea cycle and ketone bodies metabolism that contribute to energy metabolism and cancer cell proliferation.

    CONCLUSION: The crude IL-GPE can be one of the promising anticancer agents due to its selective inhibition of energy metabolism and cancer cell proliferation.

    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  7. Latifah SY, Gopalsamy B, Abdul Rahim R, Manaf Ali A, Haji Lajis N
    Molecules, 2021 Mar 12;26(6).
    PMID: 33808969 DOI: 10.3390/molecules26061554
    BACKGROUND: This study reports on the cytotoxic properties of nordamnacanthal and damnacanthal, isolated from roots of Morinda elliptica on T-lymphoblastic leukaemia (CEM-SS) cell lines.

    METHODS: MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out.

    RESULTS: Nordamnacanthal and damnacanthal at IC50 values of 1.7 μg/mL and10 μg/mL, respectively. At the molecular level, these compounds caused internucleosomal DNA cleavage producing multiple 180-200 bp fragments that are visible as a "ladder" on the agarose gel. This was due to the activation of the Mg2+/Ca2+-dependent endonuclease. The induction of apoptosis by nordamnacanthal was different from the one induced by damnacanthal, in a way that it occurs independently of ongoing transcription process. Nevertheless, in both cases, the process of dephosphorylation of protein phosphates 1 and 2A, the ongoing protein synthesis and the elevations of the cytosolic Ca2+ concentration were not needed for apoptosis to take place. Nordamnacanthal was found to have a cytotoxic effect by inducing apoptosis, while damnacanthal caused arrest at the G0/G1 phase of the cell cycle.

    CONCLUSION: Damnacanthal and nordamnacanthal have anticancer properties, and could act as potential treatment for T-lymphoblastic leukemia.

    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  8. Hariono M, Rollando R, Yoga I, Harjono A, Suryodanindro A, Yanuar M, et al.
    Molecules, 2021 Mar 08;26(5).
    PMID: 33800366 DOI: 10.3390/molecules26051464
    In our previous work, the partitions (1 mg/mL) of Ageratum conyzoides (AC) aerial parts and Ixora coccinea (IC) leaves showed inhibitions of 94% and 96%, respectively, whereas their fractions showed IC50 43 and 116 µg/mL, respectively, toward Matrix Metalloproteinase9 (MMP9), an enzyme that catalyzes a proteolysis of extracellular matrix. In this present study, we performed IC50 determinations for AC n-hexane, IC n-hexane, and IC ethylacetate partitions, followed by the cytotoxicity study of individual partitions against MDA-MB-231, 4T1, T47D, MCF7, and Vero cell lines. Successive fractionations from AC n-hexane and IC ethylacetate partitions led to the isolation of two compounds, oxytetracycline (OTC) and dioctyl phthalate (DOP). The result showed that AC n-hexane, IC n-hexane, and IC ethylacetate partitions inhibit MMP9 with their respective IC50 as follows: 246.1 µg/mL, 5.66 µg/mL, and 2.75 × 10-2 µg/mL. Toward MDA-MB-231, 4T1, T47D, and MCF7, AC n-hexane demonstrated IC50 2.05, 265, 109.70, and 2.11 µg/mL, respectively, whereas IC ethylacetate showed IC50 1.92, 57.5, 371.5, and 2.01 µg/mL, respectively. The inhibitions toward MMP9 by OTC were indicated by its IC50 18.69 µM, whereas DOP was inactive. A molecular docking study suggested that OTC prefers to bind to PEX9 rather than its catalytic domain. Against 4T1, OTC showed inhibition with IC50 414.20 µM. In conclusion, this study furtherly supports the previous finding that AC and IC are two herbals with potential to be developed as triple-negative anti-breast cancer agents.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  9. Baraya YS, Yankuzo HM, Wong KK, Yaacob NS
    J Ethnopharmacol, 2021 Mar 01;267:113522.
    PMID: 33127562 DOI: 10.1016/j.jep.2020.113522
    ETHNOPHARMACOLOGICAL RELEVANCE: Locally known as 'pecah batu', 'bayam karang', 'keci beling' or 'batu jin', the Malaysian medicinal herb, Strobilanthes crispus (S. crispus), is traditionally used by the local communities as alternative or adjuvant remedy for cancer and other ailments and to boost the immune system. S. crispus has demonstrated multiple anticancer therapeutic potential in vitro and in vivo. A pharmacologically active fraction of S. crispus has been identified and termed as F3. Major constituents profiled in F3 include lutein and β-sitosterol.

    AIM OF THE STUDY: In this study, the effects of F3, lutein and β-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model.

    MATERIALS AND METHODS: Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and β-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profile of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM).

    RESULTS: Our findings revealed significant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or β-sitosterol (TM-β) as compared with the untreated group (TM). Statistically significant reduction in body weight was observed in TM compared to the NM or treated (TM-F3, TM-L and TM-β) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause significant changes in full blood count values.

    CONCLUSION: F3 significantly reduced the total tumor burden and prevented secondary tumor development in metastatic breast cancer without significant toxicities in 4T1-induced mouse mammary carcinoma model. The current study provides further support for therapeutic development of F3 with further pharmacokinetics studies.

    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  10. Gao X, Yanan J, Santhanam RK, Wang Y, Lu Y, Zhang M, et al.
    J Food Sci, 2021 Feb;86(2):366-375.
    PMID: 33448034 DOI: 10.1111/1750-3841.15599
    Liver damage is a common liver disorder, which could induce liver cancer. Oral antioxidant is one of the effective treatments to prevent and alleviate liver damage. In this study, three flavonoids namely myricetin, isoquercitrin, and isorhamnetin were isolated and identified from Laba garlic. The isolated compounds were investigated on the protective effects against H2 O2 -induced oxidative damages in hepatic L02 cells and apoptosis inducing mechanism in hepatic cancer cells HepG2 by using MTT assay, flow cytometry and western blotting analysis. Myricetin, isoquercitrin, and isorhamnetin showed proliferation inhibition on HepG2 cells with IC50 value of 44.32 ± 0.213 µM, 49.68 ± 0.192 µM, and 54.32 ± 0.176 µM, respectively. While they showed low toxicity on normal cell lines L02. They could significantly alleviate the oxidative damage towards L02 cells (P < 0.05), via inhibiting the morphological changes in mitochondria and upholding the integrity of mitochondrial structure and function. The fluorescence intensity of L02 cells pre-treated with myricetin, isoquercitrin, and isorhamnetin (100 µM) was 89.23 ± 1.26%, 89.35 ± 1.43% and 88.97 ± 0.79%, respectively. Moreover, the flavonoids could induce apoptosis in HepG2 cells via Bcl-2/Caspase pathways, where it could up-regulate the expression of Bax and down-regulate the expression of Bcl-2, Bcl-xL, pro-Caspase-3, and pro-Caspase-9 proteins in a dose dependent manner. Overall, the results suggested that the flavonoids from Laba garlic might be a promising candidate for the treatment of various liver disorders. PRACTICAL APPLICATION: Flavonoids from Laba garlic showed selective toxicity towards HepG2 cells in comparison to L02 cells via regulating Bcl-2/caspase pathway. Additionally, the isolated flavonoids expressively barred the oxidative damage induced by H2 O2 in L02 cells. These results suggested that the flavonoids from laba garlic could be a promising agent towards the development of functional foods.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  11. Rad SK, Movafagh A
    Recent Pat Food Nutr Agric, 2021;12(1):45-57.
    PMID: 32807070 DOI: 10.2174/2212798411666200817120307
    BACKGROUND: Cinnamomum cassia (C. cassia) is an evergreen tree in China and Southern and Eastern Asia. In traditional medicine, cinnamon is widely used due to its many bioactivity effects.

    OBJECTIVE: The present novel study aims to evaluate and make a comparison of antioxidant and antiproliferative activities of different extractions of C. cassia bark using seven solvents having different polarities. Solvents polarity gradients start with the solvent of lower polarity, n-hexane, and end with water as the highest polar solvent. Among the extracts, acetone extract contains the highest phenolic and flavonoid contents; therefore, it is assessed for the ability to protect DNA from damage.

    METHODS: The extracts are evaluated for total phenolic, flavonoid contents and antioxidant activities, using FRAP, DPPH, superoxide, and hydroxyl and nitric oxide radicals scavenging assays. DNA damage protecting activity of the acetone extract is studied with the comet assay. Each of the extracts is studied for its antiproliferative effect against, MCF-7, MDA-MB-231(breast cancer), and HT29 (colon cancer), using MTT assay.

    RESULTS: The acetone extract exhibited the highest FRAP value, phenolic and flavonoids contents when compared to the other extracts and could protect 45% mouse fibroblast cell line (3T3-L1) from DNA damage at 30 μg/ml. The lowest IC50 value in DPPH, superoxide, and hydroxyl radicals scavenging was noticed in the ethyl acetate extract. IC50 value obtained for the hexane extract was the lowest compared to the other extracts in scavenging nitric oxide radicals. The hexane extract showed the highest antiproliferative effect against cancer cells followed by the chloroform extract. The ethyl acetate extract inhibited the proliferation of only MCF-7 by IC50 of 100 μg/ml, while the other extracts exhibited no IC50 in all the cancer cells.

    CONCLUSION: C. cassia showed promising antioxidant and anticancer activities with significant DNA damage protecting effect.

    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  12. Ghazali AR, Muralitharan RV, Soon CK, Salyam T, Ahmad Maulana NN, Mohamed Thaha UAB, et al.
    Asian Pac J Cancer Prev, 2020 Nov 01;21(11):3381-3386.
    PMID: 33247699 DOI: 10.31557/APJCP.2020.21.11.3381
    BACKGROUND: Traditional cooling rice powder (bedak sejuk) is a fermented rice-based cosmetic that is applied topically on one's skin, as an overnight facial mask. According to user testimonies, bedak sejuk beautifies and whitens skin, whereby these benefits could be utilised as a potential melanoma chemopreventive agent.

    OBJECTIVE: Hence, this study aimed to determine the effects of bedak sejuk made from Oryza sativa ssp. indica (Indica) and Oryza sativa ssp. japonica (Japonica) on UVB-induced B164A5 melanoma cells, and also identify the antioxidant capacities of both types of bedak sejuk.

    METHODS: The optimum dose of Indica and Japonica bedak sejuk to treat the cells was determined via the MTT assay. Then, the antioxidant capacities of both types of bedak sejuk were determined using the FRAP assay.

    RESULTS: From the MTT assay, it was found that Indica and Japonica bedak sejuk showed no cytotoxic effects towards the cells. Hence, no IC50 can be obtained and two of the higher doses, 50 and 100 g/L were chosen for treatment. In the FRAP assay, Indica bedak sejuk at 50 and 100 g/L showed FRAP values of 0.003 ± 0.001 μg AA (ascorbic acid)/g of bedak sejuk and 0.004 ± 0.0003 μg AA/g of bedak sejuk. Whereas Japonica bedak sejuk at 50 g/L had the same FRAP value as Indica bedak sejuk at 100 g/L. As for Japonica bedak sejuk at 100 g/L, it showed the highest antioxidant capacity with the FRAP value of 0.01 ± 0.0007 μg AA/g of bedak sejuk which was statistically significant (p < 0.05) when compared to other tested concentrations.

    CONCLUSION: In conclusion, Japonica bedak sejuk has a higher antioxidant capacity compared to Indica bedak sejuk despite both being not cytotoxic towards the cells. Regardless, further investigations need to be done before bedak sejuk could be developed as potential melanoma chemoprevention agents.

    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  13. Hariono M, Rollando R, Karamoy J, Hariyono P, Atmono M, Djohan M, et al.
    Molecules, 2020 Oct 14;25(20).
    PMID: 33066411 DOI: 10.3390/molecules25204691
    Matrix metalloproteinase9 (MMP9) is known to be highly expressed during metastatic cancer where most known potential inhibitors failed in the clinical trials. This study aims to select local plants in our state, as anti-breast cancer agent with hemopexin-like domain of MMP9 (PEX9) as the selective protein target. In silico screening for PEX9 inhibitors was performed from our in house-natural compound database to identify the plants. The selected plants were extracted using methanol and then a step-by-step in vitro screening against MMP9 was performed from its crude extract, partitions until fractions using FRET-based assay. The partitions were obtained by performing liquid-liquid extraction on the methanol extract using n-hexane, ethylacetate, n-butanol, and water representing nonpolar to polar solvents. The fractions were made from the selected partition, which demonstrated the best inhibition percentage toward MMP9, using column chromatography. Of the 200 compounds screened, 20 compounds that scored the binding affinity -11.2 to -8.1 kcal/mol toward PEX9 were selected as top hits. The binding of these hits were thoroughly investigated and linked to the plants which they were reported to be isolated from. Six of the eight crude extracts demonstrated inhibition toward MMP9 with the IC50 24 to 823 µg/mL. The partitions (1 mg/mL) of Ageratum conyzoides aerial parts and Ixora coccinea leaves showed inhibition 94% and 96%, whereas their fractions showed IC50 43 and 116 µg/mL, respectively toward MMP9. Using MTT assay, the crude extract of Ageratum exhibited IC50 22 and 229 µg/mL against 4T1 and T47D cell proliferations, respectively with a high safety index concluding its potential anti-breast cancer from herbal.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  14. Looi ML, Wong AKH, Gnapragasan SA, Japri AZ, Rajedadram A, Pin KY
    J Zhejiang Univ Sci B, 2020 9 8;21(9):745-748.
    PMID: 32893531 DOI: 10.1631/jzus.B2000278
    Piper betle (PB), also known as "betel" in Malay language, is a tropical Asian vine. PB leaves are commonly chewed by Asians along with betel quid. It contains phenols such as eugenol and hydroxychavicol along with chlorophyll, β-carotene, and vitamin C (Salehi et al., 2019). Extracts from PB leaves have various medicinal properties including anticancer, antioxidant, anti-inflammatory, and antibacterial effects (Salehi et al., 2019). Previous research has shown that PB induces cell cycle arrest at late S or G2/M phase and causes apoptosis at higher doses (Wu et al., 2014; Guha Majumdar and Subramanian, 2019). A combination of PB leaf extract has also been shown to enhance the cytotoxicity of the anticancer drug, 5-fluorouracil (5-FU), in cancer cells (Ng et al., 2014).
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  15. Alhuthali HM, Bradshaw TD, Lim KH, Kam TS, Seedhouse CH
    BMC Cancer, 2020 Jul 07;20(1):629.
    PMID: 32635894 DOI: 10.1186/s12885-020-07119-2
    BACKGROUND: Acute myeloid leukemia (AML) is a heterogenous hematological malignancy with poor long-term survival. New drugs which improve the outcome of AML patients are urgently required. In this work, the activity and mechanism of action of the cytotoxic indole alkaloid Jerantinine B (JB), was examined in AML cells.

    METHODS: We used a combination of proliferation and apoptosis assays to assess the effect of JB on AML cell lines and patient samples, with BH3 profiling being performed to identify early effects of the drug (4 h). Phosphokinase arrays were adopted to identify potential driver proteins in the cellular response to JB, the results of which were confirmed and extended using western blotting and inhibitor assays and measuring levels of reactive oxygen species.

    RESULTS: AML cell growth was significantly impaired following JB exposure in a dose-dependent manner; potent colony inhibition of primary patient cells was also observed. An apoptotic mode of death was demonstrated using Annexin V and upregulation of apoptotic biomarkers (active caspase 3 and cleaved PARP). Using BH3 profiling, JB was shown to prime cells to apoptosis at an early time point (4 h) and phospho-kinase arrays demonstrated this to be associated with a strong upregulation and activation of both total and phosphorylated c-Jun (S63). The mechanism of c-Jun activation was probed and significant induction of reactive oxygen species (ROS) was demonstrated which resulted in an increase in the DNA damage response marker γH2AX. This was further verified by the loss of JB-induced C-Jun activation and maintenance of cell viability when using the ROS scavenger N-acetyl-L-cysteine (NAC).

    CONCLUSIONS: This work provides the first evidence of cytotoxicity of JB against AML cells and identifies ROS-induced c-Jun activation as the major mechanism of action.

    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  16. Tan JBL, Kwan YM
    Food Chem, 2020 Jul 01;317:126411.
    PMID: 32087517 DOI: 10.1016/j.foodchem.2020.126411
    Widely used throughout the world as traditional medicine for treating a variety of diseases ranging from cancer to microbial infections, members of the Tradescantia genus show promise as sources of desirable bioactive compounds. The bioactivity of several noteworthy species has been well-documented in scientific literature, but with nearly seventy-five species, there remains much to explore in this genus. This review aims to discuss all the bioactivity-related studies of Tradescantia plants and the compounds discovered, including their anticancer, antimicrobial, antioxidant, and antidiabetic activities. Gaps in knowledge will also be identified for future research opportunities.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  17. Lee JJ, Saiful Yazan L, Kassim NK, Che Abdullah CA, Esa N, Lim PC, et al.
    Molecules, 2020 Jun 04;25(11).
    PMID: 32512700 DOI: 10.3390/molecules25112610
    Christia vespertilionis, commonly known as 'Daun Rerama', has recently garnered attention from numerous sources in Malaysia as an alternative treatment. Its herbal decoction was believed to show anti-inflammatory and anti-cancer effects. The present study investigated the cytotoxicity of the extract of root and leaf of C. vespertilionis. The plant parts were successively extracted using the solvent maceration method. The most active extract was further fractionated to afford F1-F8. The cytotoxic effects were determined using MTT assay against human breast carcinoma cell lines (MCF-7 and MDA-MB-231). The total phenolic content (TPC) of the extracts were determined. The antioxidant properties of the extract were also studied using DPPH and β-carotene bleaching assays. The ethyl acetate root extract demonstrated selective cytotoxicity especially against MDA-MB-231 with the highest TPC and antioxidant properties compared to others (p < 0.05). The TPC and antioxidant results suggest the contribution of phenolic compounds toward its antioxidant strength leading to significant cytotoxicity. F3 showed potent cytotoxic effects while F4 showed better antioxidative strength compared to others (p < 0.05). Qualitative phytochemical screening of the most active fraction, F3, suggested the presence of flavonoids, coumarins and quinones to be responsible toward the cytotoxicity. The study showed the root extracts of C. vespertilionis to possess notable anti-breast cancer effects.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  18. Nasiri R, Dabagh S, Meamar R, Idris A, Muhammad I, Irfan M, et al.
    Nanotechnology, 2020 May 08;31(19):195603.
    PMID: 31978907 DOI: 10.1088/1361-6528/ab6fd4
    The present study aims at engineering, fabrication, characterization, and qualifications of papain (PPN) conjugated SiO2-coated iron oxide nanoparticles 'IONPs@SiO2-PPN'. Initially fabricated iron oxide nanoparticles (IONPs) were coated with silica (SiO2) using sol-gel method to hinder the aggregation and to enhance biocompatibility. Next, PPN was loaded as an anticancer agent into the silica coated IONPs (IONPs@SiO2) for the delivery of papain to the HeLa cancer cells. This fabricated silica-coated based magnetic nanoparticle is introduced as a new physiologically-compatible and stable drug delivery vehicle for delivering of PPN to the HeLa cancer cell line. The IONPs@SiO2-PPN were characterized using FT-IR, AAS, FESEM, XRD, DLS, and VSM equipment. Silica was amended on the surface of iron oxide nanoparticles (IONPs, γ-Fe2O3) to modify its biocompatibility and stability. The solvent evaporation method was used to activate PPN vectorization. The following tests were performed to highlight the compatibility of our proposed delivery vehicle: in vitro toxicity assay, in vivo acute systemic toxicity test, and the histology examination. The results demonstrated that IONPs@SiO2-PPN successfully reduced the IC50 values compared with the native PPN. Also, the structural alternations of HeLa cells exposed to IONPs@SiO2-PPN exhibited higher typical hallmarks of apoptosis compared to the cells treated with the native PPN. The in vivo acute toxicity test indicated no clinical signs of distress/discomfort or weight loss in Balb/C mice a week after the intravenous injection of IONPs@SiO2 (10 mg kg-1). Besides, the tissues architectures were not affected and the pathological inflammatory alternations detection failed. In conclusion, IONPs@SiO2-PPN can be chosen as a potent candidate for further medical applications in the future, for instance as a drug delivery vehicle or hyperthermia agent.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  19. Chan EWC, Wong SK, Tangah J, Inoue T, Chan HT
    J Integr Med, 2020 May;18(3):189-195.
    PMID: 32115383 DOI: 10.1016/j.joim.2020.02.006
    Flavonoids are by far the most dominant class of phenolic compounds isolated from Morus alba leaves (MAL). Other classes of compounds are benzofurans, phenolic acids, alkaloids, coumarins, chalcones and stilbenes. Major flavonoids are kuwanons, moracinflavans, moragrols and morkotins. Other major compounds include moracins (benzofurans), caffeoylquinic acids (phenolic acids) and morachalcones (chalcones). Research on the anticancer properties of MAL entailed in vitro and in vivo cytotoxicity of extracts or isolated compounds. Flavonoids, benzofurans, chalcones and alkaloids are classes of compounds from MAL that have been found to be cytotoxic towards human cancer cell lines. Further studies on the phytochemistry and anticancer of MAL are suggested. Sources of information were PubMed, PubMed Central, ScienceDirect, Google, Google Scholar, J-Stage, PubChem and China National Knowledge Infrastructure.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  20. Seifaddinipour M, Farghadani R, Namvar F, Bin Mohamad J, Muhamad NA
    Molecules, 2020 Apr 13;25(8).
    PMID: 32295069 DOI: 10.3390/molecules25081776
    Pistacia (Pistacia vera) hulls (PV) is a health product that has been determined to contain bioactive phytochemicals which have fundamental importance for biomedical use. In this study, PV ethyl acetate extraction (PV-EA) fractions were evaluated with the use of an MTT assay to find the most cytotoxic fraction, which was found to be F13b1/PV-EA. After that, HPTLC was used for identify the most active compounds. The antioxidant activity was analyzed with DPPH and ABTS tests. Apoptosis induction in MCF-7 cells by F13b1/PV-EA was validated via flow cytometry analysis and a distinctive nuclear staining method. The representation of genes like Caspase 3, Caspase 8, Bax, Bcl-2, CAT and SOD was assessed via a reverse transcription (RT_PCR) method. Inhabitation of Tubo breast cancer cell development was examined in the BALB-neuT mouse with histopathology observations. The most abundant active components available in our extract were gallic acid and the flavonoid quercetin. The F13b1/PV-EA has antiradical activity evidence by its inhibition of ABTS and DPPH free radicals. F13b1/PV-EA displayed against MCF-7 a suppressive effect with an IC50 value of 15.2 ± 1.35 µg/mL. Also, the expression of CAT, SOD, Caspase 3, Caspase 8 and Bax increased and the expression of Bcl-2 decreased. F13b1/PV-EA dose-dependently inhibited tumor development in cancer-induced mice. Thus, this finding introduces F13b1/PV-EA as an effectual apoptosis and antitumor active agent against breast cancer.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
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