Vincristine Sulfate

Vincristine sulfate is an antitumor vinca alkaloid which inhibits microtubule formation in mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. It binds to microtubule with a Ki of 85 nM.

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Natural Products >> Alkaloid

Research Areas >> Cancer

Vincristine inhibits net addition of tubulin dimers at assembly ends of steady-state microtubules with Ki of 85 nM[1]. Vincristine stabilizes the spindle apparatus resulting in failure of the chromosomes to segregate leading to metaphase arrest and inhibition of mitosis at low concentrations. At higher concentrations, Vincristine may disrupt and induce total depolymerization of microtubules[2]. Vincristine induces apoptosis in tumor cells and inhibits SH-SY5Y cell proliferation with IC50 of 0.1 μM. Vincristine induces mitotic arrest and promots the expression of caspase-3 and -9 and cyclin B, while decreasing the expression of cyclin D[3]. Vincristine induced neurotoxicity is caused by interference with microtubule function, which results in blockage of axonal transport and thus in axonal degeneration[4].

Vincristine (3 mg/kg, i.p.) induces mean growth delay of > 120 and > 52 day, and repopulates fractions of 0.06% and 5%, administrated in mice bearing bilateral subcutaneous xenografts Rh12 or Rh18, respectively[5].

Cells are plated in 2 mL of medium in 35 mm plates at a concentration of about 5×104 cells/mL and grow for 24 h at 37°C in an atmosphere of 5% CO2 and 95% air. Then medium is replaced with fresh medium lacking or containing 4 nM drug and proliferation is continued for 3 days. Cell counts are done each day in a Coulter Counter after detaching the cells with trypsin and EDTA.

[1]. Jordan, M.A., et al. Comparison of the effects of vinblastine, vincristine, vindesine, and vinepidine on microtubule dynamics and cell proliferation in vitro. Cancer Res, 1985. 45(6): p. 2741-7.

[2]. Gidding, C.E., et al, Vincristine revisited. Crit Rev Oncol Hematol, 1999. 29(3): p. 267-87.

[3]. Donoso, J.A., et al, Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on axonal fibrillar organelles in vitro. Cancer Res, 1977. 37(5): p. 1401-7.

[4]. Horton, J.K., et al. Relationships between tumor responsiveness, vincristine pharmacokinetics and arrest of mitosis in human tumor xenografts. Biochem Pharmacol, 1988. 37(20): p. 3995-4000.

[5]. Baguley, B.C., et al, Inhibition of growth of colon 38 adenocarcinoma by vinblastine and colchicine: evidence for a vascular mechanism. Eur J Cancer, 1991. 27(4): p. 482-7.

[6]. Zhang D, et al. Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance. Int J Nanomedicine. 2017 Mar 16;12:2081-2108.

Nocodazole | Monomethyl auristatin E | VcMMAE | Mertansine | Eribulin mesylate | Epothilone D | Vinorelbine (ditartrate) | epothilone B | McMMAF | MMAF (Hydrochloride) | Ixabepilone | Taltobulin | Estramustine phosphate sodium | Ansamitocin P-3 | Combretastatin A4 disodium phosphate

MOLECULAR WEIGHT :

923.14

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1900 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1010 ug/kg

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Kidney, Ureter, Bladder - urine volume increased Blood - normocytic anemia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1700 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

>4 mg/kg

TOXIC EFFECTS :

Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

4 mg/kg

TOXIC EFFECTS :

Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Bird - chicken

DOSE/DURATION :

4 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

4500 ug/kg/21D-I

TOXIC EFFECTS :

Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1500 ug/kg/3D-I

TOXIC EFFECTS :

Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1250 ug/kg/33D-I

TOXIC EFFECTS :

Endocrine - other changes Blood - changes in bone marrow (not otherwise specified) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

4 mg/kg/4D-I

TOXIC EFFECTS :

Gastrointestinal - alteration in gastric secretion Endocrine - other changes Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

1450 ug/kg/16W-I

TOXIC EFFECTS :

Peripheral Nerve and Sensation - recording from afferent nerve Peripheral Nerve and Sensation - recording from peripheral motor nerve

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

600 ug/kg

SEX/DURATION :

male 15 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

1250 ug/kg

SEX/DURATION :

male 10 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

250 ug/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

300 ug/kg

SEX/DURATION :

female 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

250 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

250 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

250 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

250 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

750 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

Sperm Morphology

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Dominant lethal test

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Sex chromosome loss and nondisjunction

MUTATION DATA

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TEST SYSTEM :

Rodent - hamster Ovary

DOSE/DURATION :

125 ug/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 379,83,1997 *** REVIEWS *** IARC Cancer Review:Animal Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,365,1981 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,365,1981 IARC Cancer Review:Group 3 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,372,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - M2867 No. of Facilities: 33 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 1452 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - M2867 No. of Facilities: 476 (estimated) No. of Industries: 1 No. of Occupations: 8 No. of Employees: 18880 (estimated) No. of Female Employees: 13761 (estimated)