Synergists and Antagonists of Mitotic Poisons

Lettré, Hans

doi:10.1111/j.1749-6632.1954.tb45907.x

Cited by 29 publications

(6 citation statements)

References 30 publications

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“…The discovery that 6 has the ability to arrest cells at mitosis was made by Lettre et al , A natural compound screen initiated by Ye et al of known antimicrotubule assembly inhibitors, 3 , 6 , and others, illustrated common structural features that may be influential in microtubule binding. Each of the compounds described above share similar motifs; these compounds contain a hydrophobic trimethoxyphenyl group, the presence of a lactone, tropolone, or aromatic ring(s), and a small hydrophilic group such as OH or NH 2 .…”

Section: Noscapinementioning

confidence: 99%

Progress Toward the Development of Noscapine and Derivatives as Anticancer Agents

2015

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Many nitrogen-moiety containing alkaloids derived from plant origins are bioactive and play a significant role in human health and emerging medicine. Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, has been used as a cough suppressant since the mid 1950s, illustrating a good safety profile. Noscapine has since been discovered to arrest cells at mitosis, albeit with moderately weak activity. Immunofluorescence staining of microtubules after 24 h of noscapine exposure at 20 μM elucidated chromosomal abnormalities and the inability of chromosomes to complete congression to the equatorial plane for proper mitotic separation ( Proc. Natl. Acad. Sci. U. S. A. 1998 , 95 , 1601 - 1606 ). A number of noscapine analogues possessing various modifications have been described within the literature and have shown significantly improved antiprolific profiles for a large variety of cancer cell lines. Several semisynthetic antimitotic alkaloids are emerging as possible candidates as novel anticancer therapies. This perspective discusses the advancing understanding of noscapine and related analogues in the fight against malignant disease.

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Section: Noscapinementioning

confidence: 99%

Progress Toward the Development of Noscapine and Derivatives as Anticancer Agents

2015

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“…From "fiber models" (27), the mitotic apparatus has been viewed as a contractile system of the actomyosin type. In explants of chicken fibroblasts, colchicine was thought to inhibit the action of ATP (14), but this conclusion has been challenged (28). In melanocytes, Lerner and Takahashi (8) have summarized the evidence, by no means complete, for a birefringent, gelated and contractile network imbedding the melanin granules, and for the participation of ATP in the reversible gel-to-sol reaction effected by MSH.…”

Section: Colchicine Action In Relation To a Tp And Contractilementioning

confidence: 99%

On the Action of Colchicine

Malawista

1965

The Journal of Experimental Medicine

119

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This work was begun (1, 2) in an attempt to discover if there is a common basis for the therapeutic effect of colchicine ill acute gouty arthritis (3) and for its effect on the mitotic apparatus (4). Effects of colchicine have been attributed to decreased protoplasmic viscosity in both dividing (5) and resting (6, 7) cells. Experiments in cell systems hitherto employed to study colchicine action, though often elegant in design, have been technically complex and slow in operation. In the present work we have introduced a new system in which to study the action of colchicine: the frog melanocyte, x In this cell type, changes in cytoplasmic viscosity are effected rapidly and reversibly (8) and are easily controlled and measured (9, 10). Frog skin darkens when treated with melanocyte-stimulating hormone (MSH). Darkening, measured by reflectance, is due to dispersion of melanin granules in melanocytes, and is thought to be accompanied by a gel-to-sol cytoplasmic transformation. When washed, the skin lightens, with aggregation of melanin granules and cytoplasmic gelation.In using this model to study the effect of colchicine, observations were ilmde which led to a general theory of colchicine action and to the resultant possibility of using colchicine to construct biophysical models of other cell systems. MethodsPreparation of Frog Skin.--Skin from the frog Rana pipiens was prepared and mounted on rings as previously described by Shizume et al. (9). Four samples were obtained from each frog, two from the legs and two from the thighs. Thus four frogs supplied sixteen skin samples, arranged as follows, after Wright and Lerner (10).Group designed to compensate for variations in reactivity of skin from one frog to another, as well as among different areas of a given frog. Note that each group contains one skin specimen from each frog and one from each area sampled. Thus for any single experiment one control group and up to three experimental groups were available.All skin specimens were soaked in four changes of frog Ringer's solution over a period greater than 1 hour before any observations were made. (A change of Ringer's solution is also referred to as a "wash.") Measurement of Melanin Granule Dispersion.--Changes in the state of dispersion of melanin granules within melanocytes were measured as changes in reflectance when the whole skin specimen was placed over a search unit attached to a photoelectric meter. The procedure was as described previously (9), except for the establishment of the scale of reflectance: for the white enamel disc and green filter (both of which accompanied the meter), the sensitivity control knobs were set at 65. All readings of skin were taken without a filter and with the skin immersed in approximately 20 ml of solution in a 50 ml beaker. The reading of a given skin specimen after initial soaking in Ringer's solution was taken as its baseline, or zero value; subsequent increase or decrease in reflectance units was measured from basefine. Sixteen specimens could be read in a 5 minute period. T...

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“…Noscapine, a phthalide isoquinoline alkaloid, is a natural product from Papaver somniferum (Opium poppy) and is being widely used as an antitussive agent in many countries (Empey et al, 1979;Karlsson et al, 1990;Padma et al, 2013). Noscapine is known for its mitotic poisoning effect (Lettre, 1954). It is known that noscapine is also capable of inducing apoptosis through the activation of various pathways in different cancer cell lines (DeBono et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

9‐Ethynyl noscapine induces G2 /M arrest and apoptosis by disrupting tubulin polymerization in cervical cancer

et al. 2021

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Noscapine is a phthalide isoquinoline alkaloid present in the latex of Papaver somniferum and has demonstrated potent antitumor activity in various cancer models. Structural changes in the core molecule of noscapine architecture have produced a number of potent analogs. We have recently synthesized the novel noscapine analogs (3, 4, and 5) with different functional groups appended at ninth position of natural noscapine. The anticancer activity of these compounds has been investigated using various human cancer cell lines such as HeLa (cervical cancer), DU‐145 (prostate cancer), MCF‐7 (breast cancer), and IMR‐32 (neuroblastoma). One of the compounds in this series, 9‐ethynyl noscapine (5), has demonstrated good anticancer activity against HeLa cells. Biological studies demonstrated that compound 5 decreased cell viability and colony formation in HeLa cells in a concentration dependent manner. To further uncover the mechanism in detail, we evaluated compound 5 effect on cell cycle progression, microtubule dynamics, and apoptosis. Cell cycle and western blotting analysis revealed that 9‐ethynyl noscapine treatment resulted in cell cycle arrest at G2/M and decreased CDK1 and cyclinB1 protein expression. We also observed that 9‐ethynyl noscapine (5) treatment leads to disruption in tubulin polymerization and induction of apoptosis by decreasing expression of bcl2, pro‐caspase 3, and activation of cytochrome C. Taken together, our results indicate that 9‐ethynyl noscapine (5) effectively supresses the growth of cervical cancer cells (HeLa) by disrupting tubulin polymerization, cell cycle progression leading to apoptosis.

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Synergists and Antagonists of Mitotic Poisons

Cited by 29 publications

References 30 publications

Progress Toward the Development of Noscapine and Derivatives as Anticancer Agents

Progress Toward the Development of Noscapine and Derivatives as Anticancer Agents

On the Action of Colchicine

9‐Ethynyl noscapine induces G2 /M arrest and apoptosis by disrupting tubulin polymerization in cervical cancer

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