Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Podophyllotoxin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMedDate not supplied

[A model-based comparison of cost effectiveness of imiquimod versus podophyllotoxin for the treatment of external anogenital warts in France].

OBJECTIVES: For the National health scheme, to compare the costs and the efficacy of treatment of external anogenital warts with imiquimod and podophyllotoxin and laser therapy in the case of failure or relapse. PATIENTS AND METHODS: A model simulating the two successive treatments was built. In the first phase, the two topical treatments applied by the patients: podophyllotoxin for 4 weeks and imiquimod for 16 weeks were compared. In the case of failure or relapse, laser therapy that is widely used in France in this indication and, was applied. The efficacy of the topical treatments was assessed after reanalysis of the results of two controlled clinical trials versus placebo. These two trials were retained because they were comparable in method and had been recently published at the same time. A review of the literature assessed the results of laser therapy. A survey was conducted to collect the medical resources consumed by the different treatments. RESULTS: Imiquimod provided a clearance rate of 49.5 p. 100, i.e., the disappearance of the lesions at 16 weeks, greater than that of podophyllotoxin (28.3 p. 100) at 4 weeks. The relapse rate was lowest with imiquimod (13.3 p. 100) than with podophyllotoxin (30.9 p. 100). The remission rate without relapse 3 months after the end of treatment was, including the laser, of 62 p. 100 following imiquimod and of 47 p. 100 following podophyllotoxin. The costs per patient cured was of 668 Euros for imiquimod and of 689 Euros for podophyllotoxin. CONCLUSION: Imiquimod, because of its greater initial efficacy, is at least as cost-effective as podophyllotoxin the treatment of external genital warts.

Adjuvants, Immunologic↗
PubMed2002

Production of podophyllotoxin by plant cell cultures of Podophyllum hexandrum in bioreactor.

Submerged cultivation of Podophyllum hexandrum for the production of podophyllotoxin was carried out in a 3l stirred tank bioreactor fitted with a low-shear Setric impeller. The specific requirements of the medium, such as carbon source (sugar) and light, were established for the growth of and podophyllotoxin production by P. hexandrum in suspension cultures. Substitution of sucrose by glucose resulted in higher growth and podophyllotoxin production. The biosynthesis of podophyllotoxin was favored when plant cells were cultivated in the dark. An agitation speed of 100 rpm was sufficient to mix the culture broth in the bioreactor without causing any significant cell damage. Biomass and podophyllotoxin accumulation in 3 l bioreactor under batch growth conditions were 6.5 g/l and 4.26 mg/l, respectively, in 22 d. This resulted in an overall podophyllotoxin productivity of 0.19 mg/(l.d), which represented an increase of 27% in comparison to its productivity in a shake flask. Podophyllotoxin production was found to be a combined growth-associated and non-growth associated process.

Journal Article↗
PubMed1986

Inhibition of respiration in mitochondria and in digitonin-treated rat hepatocytes by podophyllotoxin.

The effects of the microtubular inhibitor, podophyllotoxin, on mitochondrial respiration were determined using isolated, digitonin-permeabilized hepatocytes and isolated mitochondria. In hepatocytes, podophyllotoxin (1.5 mM) inhibited coupled and uncoupled respiration of both FAD and NAD-linked substrates. In mitochondria, podophyllotoxin inhibited State III respiration, prevented the return to State IV respiration, and inhibited uncoupled respiration. There was no inhibition of ascorbate/TMPD oxidation in either the hepatocytes or the mitochondria. Podophyllotoxin had no effect upon oligomycin inhibition of coupled respiration. Oligomycin had no effect on the podophyllotoxin-inhibition of uncoupled respiration in either hepatocytes or mitochondria. The results indicate that podophyllotoxin alters electron flow at a site early in the electron transport chain.

Animals↗
PubMed1982

VP16-213 and podophyllotoxin. A study on the relationship between chemical structure and biological activity.

VP16-213, a semi-synthetic derivative of podophyllotoxin, is an effective antitumor agent in the treatment of a variety of leukemias and solid tumors. A comparison of the mechanism of action of VP16-213 and podophyllotoxin has revealed that although both drugs inhibit the uptake of nucleosides into HeLa cells, they exhibit other biological properties which are quite distinct. Podophyllotoxin is a potent inhibitor of microtubule assembly in vitro, while VP16-213 has no effect in this system. VP16-213 induces single stranded breaks in HeLa cells DNA, an effect which may be related to its antitumor activity. In contrast to VP16-213 treated cells, podophyllotoxin-treated cells maintain DNA integrity. Structure-activity relationship studies have identified some of chemical sites of VP16-213 and podophyllotoxin responsible for each of their biological properties. These studies illustrate that chemical modification of podophyllotoxin can generate derivatives which possess new and unique biological properties.

Animals↗
PubMed1991

Expression of c-myc proto-oncogene during podophyllotoxin induced IW32 erythroleukemia cell differentiation.

The effect of hemin or podophyllotoxin on the differentiation of the erythropoietin (epo)-producing IW32 erythroleukemia cells was investigated. Podophyllotoxin induced IW32 cells to differentiate, and hemin potentiated the differentiation. Hemin had no effect on cell proliferation whereas podophyllotoxin inhibited cell growth. c-myc mRNA levels decreased biphasically by hemin or podophyllotoxin, while the combined treatment of hemin plus podophyllotoxin did not result in the initial decrease in c-myc mRNA level. Our data suggested that down-regulation of c-myc expression was not a prerequisite of IW32 cell differentiation induced by hemin and podophyllotoxin combined.

Animals↗
PubMed1976

Effects of podophyllotoxin and VP-16-213 on microtubule assembly in vitro and nucleoside transport in HeLa cells.

VP-16-213, a semisynthetic derivative of podophyllotoxin, is an active antitumor agent. In this paper, the effects of VP-16-213 and podophyllotoxin on microtubule assembly in vitro and nucleoside transport in HeLa cells are compared. At 100 muM, VP-16-213 does not inhibit microtubule assembly in vitro, while 5 muM podophyllotoxin completely prevents the formation of microtubules. The presence of the glucoside moiety in VP-16-213 is responsible for the inactivity of VP-16-213 in this system because 4'-demethylepipodo-phyllotoxin, the nonglucoside congener of VP-16-213, inhibits microtubule assembly. In HeLa cells, VP-16-213 and podophyllotoxin share a common biological property; both agents inhibit the uptake of thymidine and uridine into cells by inhibiting the facilitated diffusional component of nucleoside transport. The conncentrations of drug necessary to inhibit thymidine and uridine uptake into HeLa cells by 50% are 10 and 5 muM, respectively, for podophyllotoxin, and 25 and 20 muM for VP-16-213. The action of podophyllotoxin on nucleoside transport appears unrelated to its effect on microtubule assembly, since VP-16-213, which does not inhibit microtubule assembly, inhibits nucleoside transport.

Adenosine↗
PubMed2006

Frequency and timing of leaf removal affect growth and podophyllotoxin content of Podophyllum peltatum in full sun.

Podophyllotoxin is a pharmaceutical compound found in leaves and rhizomes of American mayapple (P. peltatum L.), a species being investigated as an alternative to that of the Indian mayapple (P. emodi). Leaves alone can serve as a renewable source of podophyllotoxin (and other lignans) leaving rhizomes undisturbed to produce leaf biomass in subsequent years. It is not known, however, how frequently or severely plants can be defoliated without adversely affecting future plant growth, lignan content, or podophyllotoxin yield (g.m(-2)). This study compared harvest strategies that were mild to severe in frequency and timing of leaf removal. A wild population in full sun was subjected to leaf removal treatments of varying frequency (every year, every 2nd or 3rd year) and timing (early or late). Control plots not previously harvested were included every year. Plots were 1.0 m2 and established during spring of 2001. Duration of the study was four years. P. peltatum plants did not tolerate the most severe harvest treatment: annual harvest frequency in combination with early harvest time. Early annual harvests reduced total leaf dry mass and total leaf area in a consistent and linear manner. In contrast, plants tolerated annual harvests when conducted late in the growing season and tolerated early harvests when conducted every 2nd or 3rd year. The number of sexual shoots was reduced to zero by early annual harvests. Podophyllotoxin content was 2.7 to 6.5 times greater in leaves harvested early compared to those harvested late, though content was significantly greater in only two out of four years. In conclusion, we can recommend leaf removal every year from well-established P. peltatum populations grown in full sun if harvests are conducted late in the growing season. This harvest strategy ensures maximum podophyllotoxin yield without jeopardizing future leaf biomass yield. Leaves harvested early appear to have greater podophyllotoxin content, but we discourage early harvest every year. Instead, our results indicate that leaves can be harvested early every other year without reducing long-term performance of P. peltatum populations.

Agriculture↗
PubMed2003

Er:YAG laser followed by topical podophyllotoxin for hard-to-treat palmoplantar warts.

BACKGROUND AND OBJECTIVES: Palmoplantar warts are often hard to treat. They tend to relapse and the course of therapy is frustrating in many cases. The erbium:YAG laser(Er:YAG) with a wavelength of 2.94 rm is capable of achieving a rapid and precise ablation of warts, but about 14% of patients are non-responders as shown in a previous study. Podophyllotoxin is an established antimitotic agent derived from podophyllum plant resin, approved for human papilloma virus (HPV)-induced genital warts. The combination of both ablative Er:YAG laser and topical 0.5% podophyllotoxin solution in hard-to-treat palmoplantar HPV warts was investigated. PATIENTS AND METHODS: Thirty-five patients with hard-to-treat warts(palmar or plantar) with a mean age of (32.2+12.1) years, range 17-50 years, with various pretreatments that had failed, were treated once by Er:YAG laser ablation with a spot size of 3 mm, a frequency between 8 Hz and 10 Hz, and a fluence of 5.7-11.3 J/cm2. After wound healing, topical podophyllotoxin 0.5% solution was applied for 3 days followed by a break of 4 days. Four to six treatment cycles with podophyllotoxin were performed. RESULTS: After laser treatment followed by topical podophyllotoxin cream a complete response was observed in 31 patients (88.6%). Two patients with plantar warts and a complete response showed a relapse within 3 months after treatment (5.7%). None of the patients developed pigmentary changes,wound infections or scarring. CONCLUSION: The therapy of hard-to-treat warts with a combination of Er:YAG laser and topical podophyllotoxin is safe and effective. Compared with laser alone, the CR percentage seems to be higher and the percentage of relapses reduced.

Administration, Topical↗
PubMed2005

Synthesis and identification of antigenic conjugates of podophyllotoxin.

AIM: To synthesize and identify artificial antigen of podophyllotoxin for the production of podophyllotoxin polyclonal antibody. METHODS: The hapten was synthesized by two different chemical approaches and characterized by TLC, IR, NMR, and MS. Mixed anhydride reaction (MAR) and active ester method (AEM) were used to couple the podophyllotoxin to carrier proteins (BSA and OVA). Characterization of artificial antigens was done by using spectroscopy and electrophoresis. The anti-podophyllotoxin polyclonal antibodies were obtained through immunizing rabbits. RESULTS: The results from IR, NMR and MS showed that 4-O-succinoyl podophyllotoxin (hapten) was successfully synthesized. The coupling molar ratios of the hapten and carrier proteins were 88.6 for Hapten-BSA1, 40.3 for Hapten-BSA2, 17.8 for Hapten-OVA1, and 54.2 for Hapten-OVA2. Hapten conjugates coupled with BSA yielded two sets of the specific and affinitive polyclonal antibodies. One set of antibodies showed an IC50 value of 2.21 microg.mL(-1) with a detection limit of 0.12 microg.mL(-1). CONCLUSION: Antigenic conjugates were artificially synthesized, and based on these artificial antigens, polyclonal antibodies against podophyllotoxin were raised from rabbits immunized with two different immunogens and characterized with an indirect ELISA format.

Animals↗
PubMed1981

Incorporation of radioactive tubulin into microtubules at steady state. Experimental and theoretical analysis of the effect of podophyllotoxin.

Addition of a substoichiometric amount of podophyllotoxin to microtubules which are at steady state decreases the rate of incorporation of radioactive subunits into the microtubules. The magnitude of this effect depends on the fraction of the total number of each of the microtubule ends which is capped by tubulin-podophyllotoxin subunits; these fractions depend on the concentration of podophyllotoxin used. A quantitative relationship is presented which correlates the extent of tubulin-podophyllotoxin capping of the microtubule ends with alterations in the rate for steady state subunit incorporation. An analysis based upon this relationship reveals that tubulin-podophyllotoxin caps both ends of the microtubule. Previously proposed mechanisms which involve tubulin-podophyllotoxin capping at only one end of the microtubule are analyzed.

Animals↗
PubMed2005

Development of an enzyme-linked immunosorbent assay for podophyllotoxin.

A competitive indirect enzyme-linked immunosorbent assay (ciELISA) for podophyllotoxin was developed by using polyclonal antibody, and its suitability for the determination of this analyte in spiked water samples was studied. To avoid antibody production to the linker, the succinoyl-podophyllotoxin (hapten) mimicking the analyte was synthesized and conjugated with the carrier proteins bovine serum albumin (BSA) and ovalbumin (OVA) by mixed anhydride reaction (MAR) and active ester method (AEM). Polyclonal antibodies raised against Hapten-BSA(1) synthesized by MAR and Hapten-BSA(2) by AEM were screened and selected for the ciELISA. One set of antibodies from the rabbit M4440 immunized with Hapten--BSA(1) showed an I(50) value of 2.21 microg/mL with a detection limit of 0.12 microg/mL, and the other set from the rabbit M4469 immunized with Hapten-BSA(2) had an I(50) value of 0.7897 microg/mL with a detection limit of 0.0056 microg/mL. This assay showed the cross-reactivities with the structurally closely related compounds. Recoveries from the podophyllotoxin-fortified tap water in the assay were in the range of 72--115%. A good correlation between podophyllotoxin concentration measured by the ELISA and HPLC (R(2)=0.9924, Y=1.195X-0.257) was obtained from linear regression analysis. These results indicate that the ELISA could be a convenient and supplemental analytical tool for monitoring podophyllotoxin and its analogues in waters without previous extraction or cleanup.

Animals↗
PubMedDate not supplied

Production of podophyllotoxin using cross-species coculture of Linum flavum hairy roots and Podophyllum hexandrum cell suspensions.

Novel cross-species coculture systems using Linum flavum hairy roots and Podophyllum hexandrum cell suspensions were applied for in vitro production of podophyllotoxin. The hairy roots and suspensions were cocultured in Linsmaier and Skoog medium in dual shake flasks and dual bioreactors. In separate experiments, coniferin feeding was shown to be an effective strategy for increasing the accumulation of podophyllotoxin in P. hexandrum suspensions. Because roots of L. flavum are a natural source of coniferin, hairy roots of this species were used in coculture with P. hexandrum to provide an in situ supply of coniferin. Compared with P. hexandrum suspensions cultured alone in shake flasks or bioreactors, podophyllotoxin concentrations in cocultured P. hexandrum cells were increased by 240% and 72% in dual shake flask and dual bioreactor systems, respectively. The availability and stability of coniferin in the medium are the most likely factors limiting podophyllotoxin synthesis in coculture. Intensification of the coculture process is required to further improve total podophyllotoxin accumulation on a volumetric basis.

Bioreactors↗
PubMed2002

Evaluation of Podophyllum peltatum accessions for podophyllotoxin production.

In an effort to develop a sustainable source of podophyllotoxin for the production of anticancer drugs such as etoposide, teniposide and etopophos, Podophyllum peltatum accessions with podophyllotoxin-rich leaf biomass were identified and transplanted to different growing conditions by vegetative cuttings. Results indicate that the lignan profile in leaves does not change over time or due to environment conditions. Podophyllotoxin and alpha-peltatin content in the blades seems to be stable with an inverse relationship of concentration between these compounds. A podophyllotoxin-rich leaf accession showed low biosynthetic capability to synthesize alpha- and beta-peltatin and the converse was also true, indicating that selection and cultivation of high-yielding podophyllotoxin leaf biomass may reduce production costs.

Biomass↗
PubMed2003

Variation of podophyllotoxin in leaves of Eastern Red Cedar (Juniperus virginiana).

Leaves of Eastern red cedar (Juniperus virginiana L. Cupressaceae) have been reported to contain podophyllotoxin, a pharmaceutical compound used to manufacture drugs for treatment of cancer, rheumatoid arthritis, genital warts, psoriasis, and multiple sclerosis. Podophyllotoxin content of leaves of immature, mature male, and mature female plants (approximately 1.45 mg x g -1) was significantly higher than that of leaves of juvenile plants (0.60 mg x g -1). Sampling date also affected podophyllotoxin content. Leaves harvested in January and April exhibited higher podophyllotoxin contents (1.56 and 1.45 mg x g -1, respectively) than leaves harvested in February and June (1.06 and 1.08 mg x g -1, respectively). There was no obvious pattern or trend in the data due to sampling date. There was no significant interaction between plant type and sampling date. These results indicate that foliage of mature Eastern red cedar, a waste product of the lumber industry, could be a low-yielding, but relatively stable, source of podophyllotoxin.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Self-treatment of female external genital warts with 0.5% podophyllotoxin cream (Condyline) vs weekly applications of 20% podophyllin solution.

Sixty women with genital warts were randomly allocated to treatment with either weekly application of 20% podophyllin solution or self-treatment with 0.5% podophyllotoxin cream twice daily for three days in weekly intervals. After a maximum of 4 treatment cycles a final assessment was carried out after 3 months. Primary clearance after termination of treatment was 82% for podophyllotoxin and 59% for podophyllin solution. After excluding relapses at the 3-month follow-up, final clearance for podophyllotoxin (71%) was significantly better (P < 0.05) than that for podophyllin solution (48%). The total frequency of warts eradicated was 94% with podophyllotoxin and 74% with podophyllin solution (P < 0.001). Local adverse effects were generally mild or moderate. Podophyllotoxin cream provides a mode of easy application for women with external genital warts and had in this study a significantly better effect than podophyllin solution.

Administration, Cutaneous↗
PubMed2001

Two new podophyllotoxin glucosides from Sinopodophyllum emodi (Wall.) Ying.

Two new aryltetralin-type lignans, isopodophyllotoxin 7'-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (1) and 4-demethyl-picropodophyllotoxin 7'-O-beta-D-glucopyranoside (2), along with eight known podophyllotoxin derivatives: 4-demethyl-podophyllotoxin 7'-O-beta-D-glucopyranoside (3), podophyllotoxin 7'-O-beta-D-glucopyranoside (4), deoxypodophyllotoxin (5), picropodophyllotoxin (6), podophyllotoxin (7), 4-demethyl-picropodophyllotoxin (8), 4-demethyl-podophyllotoxin (9), and 4-demethyl-deoxypodophyllotoxin (10), were isolated from the roots and rhizomes of Sinopodophyllum emodi (Wall.) Ying (Berberidaceae). Their structures were identified based on NMR spectral data and chemical evidence.

Glucosides↗
PubMed1991

[Preliminary report of podophyllotoxin in the treatment of genital warts in China].

Sixty-five patients with various types of genital warts were treated with 0.5% podophyllotoxin ethanol solution provided by Conpharm AB Sweden including 49 male and 16 female patients. The patients were treated topically bid, for 3 days as one treatment. If the desired effect was not achieved following one treatment, it was repeated in weekly intervals for no more than 3 treatments. Cumulative cure rates of 73.85%, 80% and 81.54% were obtained with podophyllotoxin treatment after the 1st, 2nd and 3rd treatments respectively. The genital warts cured by podophyllotoxin relapsed after one month at a rate of 14.9%. None of the patients treated with podophyllotoxin showed any systemic side effects, but mild local superficial erosions and slight pain appeared in most of the patients on the 3rd day of therapy. It is our opinion that external use of 0.5% podophyllotoxin for treating genital warts should be the method of choice for its high cure rate, time saving, safety and convenience.

Administration, Topical↗
PubMed1984

4'-Demethylepipodophyllotoxin-beta-D-glucoside: a new podophyllotoxin derivative with VM-26-like and VP-16-213-like activities.

Mutants of Chinese hamster ovary (CHO) cells independently selected for resistance to the anticancer drug 4'-demethylepipodophyllotoxin thenylidene-beta-D-glucoside (VM-26) and the microtubule inhibitor podophyllotoxin exhibit mutually an exclusive cross-resistance pattern toward various podophyllotoxin derivatives that possess either VM-26-like or podophyllotoxin-like activities, respectively. The cross-resistance studies with these mutants have led to the identification of a new podophyllotoxin derivative, 4'-demethylepipodophyllotoxin-beta-D-glucoside (compound No. 13), which possesses VM-26-like and 4'-demethylepipodophyllotoxin ethylidene-beta-D-glucoside (VP-16-213)-like activity. This inference is strongly supported by our observation that, like VM-26 and VP-16-213, compound No. 13 showed no antimitotic activity (as seen by the effect on the mitotic index) but was highly active in inducing DNA strand breaks, sister chromatid exchanges, and mutations at the hypoxanthine-guanine phosphoribosyl transferase and adenosine kinase loci in CHO cells. On the basis of structure-activity data of various podophyllotoxin derivatives, three structural features have been identified that appear essential for VM-26-like activity. These are: 1) the presence of an hydroxyl group at the 4'-carbon, 2) an epi-configuration at the C-4 position, and 3) the presence of a glycoside moiety on the hydroxyl group at the C-4 position. In addition, the nature of the glycoside substituents at the C-4 position greatly affects the relative VM-26-like activity of various compounds.

Animals↗