Natural Sesquiterpenoids as Cytotoxic Anticancer Agents

Chen, Qi-Feng; Liu, Z.-P.; Wang, F.-P.

doi:10.2174/138955711797655399

Cited by 50 publications

(32 citation statements)

References 40 publications

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“…The lack of selectivity is one of the major drawbacks in many of these drugs except for a limited number of anticancer medications such as "vemurafenib" that show their effects on melanoma cells with V600E BRAF mutation and monoclonal antibodies that specifically target cancer antigens [8]. The heterogeneous nature of cancers and multidrug resistance causes the development of anticancer drugs a challenging task [9]. Fucoidans, by far, have been recognized as a biocompatible substance that indicates positive biological responses.…”

Section: Introductionmentioning

confidence: 99%

Fucoidan Purified from Sargassum polycystum Induces Apoptosis through Mitochondria-Mediated Pathway in HL-60 and MCF-7 Cells

et al. 2020

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Fucoidans are biocompatible, heterogeneous, and fucose rich sulfated polysaccharides biosynthesized in brown algae, which are renowned for their broad-spectrum biofunctional properties. As a continuation of our preliminary screening studies, the present work was undertaken to extract polysaccharides from the edible brown algae Sargassum polycystum by a modified enzyme assisted extraction process using Celluclast, a food-grade cellulase, and to purify fucoidan by DEAE-cellulose anion exchange chromatography. The apoptotic and antiproliferative properties of the purified fucoidan (F5) were evaluated on HL-60 and MCF-7 cells. Structural features were characterized by FTIR and NMR analysis. F5 indicated profound antiproliferative effects on HL-60 leukemia and MCF-7 breast cancer cells with IC50 values of 84.63 ± 0.08 µg mL−1 and 93.62 ± 3.53 µg mL−1 respectively. Further, F5 treatment increased the apoptotic body formation, DNA damage, and accumulation of HL-60 and MCF-7 cells in the Sub-G1 phase of the cell cycle. The effects were found to proceed via the mitochondria-mediated apoptosis pathway. The Celluclast assisted extraction is a cost-efficient method of yielding fucoidan. With further studies in place, purified fucoidan of S. polycystum could be applied as functional ingredients in food and pharmaceuticals.

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Section: Introductionmentioning

confidence: 99%

Fucoidan Purified from Sargassum polycystum Induces Apoptosis through Mitochondria-Mediated Pathway in HL-60 and MCF-7 Cells

et al. 2020

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“…Mansonones are, biosynthetically, thought to be phytoalexins produced by the injury of bark of some plants such as American elm ( Ulmus minor ). Mansonones E and F were reported to possess a potent cytotoxic effect on HeLa, human malignant melanoma A357-S2, MCF-7 and human histocytic lymphoma U937 cell lines [ 3 , 4 ]. In addition, antileukemic and topoisomerase inhibitory effects were reported to mansonone E. However, other mansonones such as mansones A–D, G, I–S were not investigated for their possible cytotoxic effects on several cell lines despite their structural similarity to that of mansones E and F [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Anticancer Profiling for Coumarins and Related O-Naphthoquinones from Mansonia gagei against Solid Tumor Cells In Vitro

et al. 2018

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Napthoquinones and coumarins are naturally occurring compounds with potential anticancer activity. In the current study, two O-naphthoquinons (mansonone-G and mansonone-N) and six coumarins (mansorin-A, mansorin-B, mansorin-C, mansorins-I, mansorin-II, and mansorin-III) were isolated from the heartwood of Mansonia gagei family Sterculariaceae. Isolated compounds were examined for their potential anticancer activity against breast (MCF-7), cervix (HeLa), colorectal (HCT-116) and liver (HepG2) cancer cells using Sulfarhodamine-B (SRB) assay. Mansorin-II and mansorin-III showed relatively promising cytotoxic profile in all cell lines under investigation with inhibitory concentrations (IC50s) in the range of 0.74 µM to 36 µM and 3.95 µM to 35.3 µM, respectively. In addition, mansorin-B, mansorin-C, mansorin-II and mansorin-III significantly increased cellular entrapment of the P-glycoprotein (P-gp) substrate, doxorubicin, in colorectal cancer cells expressing the P-gp pump. The inhibitory effect of the isolated compounds on P-gp pump was examined using human recombinant P-gp molecules attached to ATPase subunit. Mansorin-B and mansonone-G were found to inhibit the P-gp attached ATPase subunit. On the other hand, mansorin-C, mansorin-III and mansorin-II inhibited P-gp pump via dual action (P-gp related ATPase subunit inhibition and P-gp substrate binding site occupation). However, mansorin II was examined for its potential chemomodulatory effect to paclitaxel (PTX) against colorectal cancer cells (HCT-116 and CaCo-2). Mansorin-II significantly reduced the IC50 of PTX in HCT-116 cells from 27.9 ± 10.2 nM to 5.1 ± 1.9 nM (synergism with combination index of 0.44). Additionally, Mansorin-II significantly reduced the IC50 of PTX in CaCo-2 cells from 2.1 ± 0.8 µM to 0.13 ± 0.03 µM (synergism with combination index of 0.18). Furthermore, cell cycle analysis was studied after combination of mansorin-II with paclitaxel using DNA flow cytometry analysis. Synergism of mansorin-II and PTX was reflected in increasing apoptotic cell population in both HCT-116 and CaCo-2 cells compared to PTX treatment alone. Combination of mansorin-II with PTX in CaCo-2 cells significantly increased the cell population in G2/M phase (from 2.9 ± 0.3% to 7.7 ± 0.8%) with reciprocal decrease in G0/G1 cell fraction from 52.1 ± 1.1% to 45.5 ± 1.0%. Similarly in HCT-116 cells, mansorin-II with PTX significantly increased the cell population in G2/M phase (from 33.4 ± 2.8% to 37.6 ± 1.3%) with reciprocal decrease in the S-phase cell population from 22.8 ± 1.7% to 20.2 ± 0.8%. In conclusion, mansorin-II synergizes the anticancer effect of paclitaxel in colorectal cancer cells, which might be partially attributed to enhancing its cellular entrapment via inhibiting P-gp efflux pump.

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“…The flavonoid hispidulin, present in A. elatior , has been tested for cytotoxic activity against Jurkat E6-1, GLC4, and COLO320 cells, showing IC 50 ranging from 10.21 to 24.62 μ g/mL [ 57 , 58 ]. Other constituents of this plant, dihydroparthenolide and psilostachyin, were reported as inactive when tested against KB cells [ 59 ]; the same as was found for damsinic acid tested against U937, Jurkat and Molt 4 [ 60 ], while psilostachyin C showed no effectiveness against HeLa, MCF-7, or A431 cell lines [ 61 ] but was slightly effective against BW5147 cells, with an IC 50 value of 4.89 μ g/mL [ 62 ]. Chlorogenic acid showed IC 50 values ranging from 1.8–10.7 μ g/mL against HepG2, Hep2, HCT116, RD, and MCF7 [ 63 ].…”

Section: Resultsmentioning

confidence: 89%

Cytotoxic Activity of Extracts from Plants of Central Argentina on Sensitive and Multidrug‐Resistant Leukemia Cells: Isolation of an Active Principle from Gaillardia megapotamica

González

Joray

Laiolo

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Plants are a significant reservoir of cytotoxic agents, including compounds with the ability to interfere with multidrug-resistant (MDR) cells. With the aim of finding promising candidates for chemotherapy, 91 native and naturalized plants collected from the central region of Argentina were screened for their cytotoxic effect toward sensitive and MDR P-glycoprotein (P-gp) overexpressing human leukemia cells by means of MTT assays. The ethanol extracts obtained from Aldama tucumanensis, Ambrosia elatior, Baccharis artemisioides, Baccharis coridifolia, Dimerostemma aspilioides, Gaillardia megapotamica, and Vernonanthura nudiflora presented outstanding antiproliferative activity at 50 μg/mL, with inhibitory values from 93 to 100%, when tested on the acute lymphoblastic leukemia (ALL) cell line CCRF-CEM and the resistant derivative CEM-ADR5000, while 70–90% inhibition was observed against the chronic myelogenous leukemia (CML) cell K562 and its corresponding resistant subline, Lucena 1. Subsequent investigation showed these extracts to possess marked cytotoxicity with IC50 values ranging from 0.37 to 29.44 μg/mL, with most of them being below 7 μg/mL and with ALL cells, including the drug-resistant phenotype, being the most affected. G. megapotamica extract found to be one of the most effective and bioguided fractionation yielded helenalin (1). The sesquiterpene lactone displayed IC50 values of 0.63, 0.19, 0.74, and 0.16 μg/mL against K562, CCRF-CEM, Lucena 1, and CEM/ADR5000, respectively. These results support the potential of these extracts as a source of compounds for treating sensitive and multidrug-resistant leukemia cells and support compound 1 as a lead for developing effective anticancer agents.

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Natural Sesquiterpenoids as Cytotoxic Anticancer Agents

Cited by 50 publications

References 40 publications

Fucoidan Purified from Sargassum polycystum Induces Apoptosis through Mitochondria-Mediated Pathway in HL-60 and MCF-7 Cells

Fucoidan Purified from Sargassum polycystum Induces Apoptosis through Mitochondria-Mediated Pathway in HL-60 and MCF-7 Cells

Anticancer Profiling for Coumarins and Related O-Naphthoquinones from Mansonia gagei against Solid Tumor Cells In Vitro

Cytotoxic Activity of Extracts from Plants of Central Argentina on Sensitive and Multidrug‐Resistant Leukemia Cells: Isolation of an Active Principle from Gaillardia megapotamica

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