Vinblastine Sulfate

Vinblastine sulfate is a cytotoxic alkaloid used against various cancer types. Vinblastine sulfate inhibits the formation of microtubule and suppresses nAChR with an IC50 of 8.9 μM.

Signaling Pathways >> Autophagy >> Autophagy

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

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Natural Products >> Alkaloid

Research Areas >> Cancer

IC50: 8.9 μM(nAChR)[1]

Vinblastine does not depolymerize spindle microtubules, yet it powerfully blocks mitosis (for example, IC50 0.8 nM in HeLa cells) and cells die by apoptosis[2]. In NB4 cells, vinblastine produces alteration of p53 and DNA fragmentation. Vinblastine treatment has an antiproliferative effect via the induction of apoptosis producing Bax/Bcl-2 imbalance. Vinblastine treatment suppresses NFκB expression and depresses NFκB-DNA binding activity while maintaining JNK activation that subsequently results in apoptotic response through caspase-dependent pathway[3]. Vinblastine is found to trigger apoptosis as evidenced by the loss of mitochondrial membrane potential, the release of both cytochrome c and apoptosis inducing factor, activation of caspase-9 and 3, and cleavage of Poly (ADP-ribose)-Polymerase[4].

Vinblastine is a widely used anticancer drug with undesired side effects. Its conjugation with carrier molecules could be an efficient strategy to reduce these side effects[5].

[1]. McKay DB, et al. Nicotinic and nonnicotinic receptor-mediated actions of vinblastine. Proc Soc Exp Biol Med. 1993 Jul;203(3):372-6.

[2]. Pandya P, et al. Molecular recognition pattern of cytotoxic alkaloid vinblastine with multiple targets. J Mol Graph Model. 2014 Nov;54:1-9.

[3]. Calviño E, et al. JNK and NFκB dependence of apoptosis induced by vinblastine in human acute promyelocytic leukaemia cells. Cell Biochem Funct. 2015 Jun;33(4):211-9.

[4]. Selimovic D, et al. Vinblastine-induced apoptosis of melanoma cells is mediated by Ras homologous A protein (Rho A) via mitochondrial and non-mitochondrial-dependent mechanisms. Apoptosis. 2013 Aug;18(8):980-97.

[5]. Bánóczi Z, et al. Synthesis and in vitro antitumor effect of vinblastine derivative-oligoarginine conjugates. Bioconjug Chem. 2010 Nov 17;21(11):1948-55.

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 :

909.16

WISWESSER LINE NOTATION :

T C6 B5665/BS 2AB S BX IN QN NU&&TTTJ FO1 I1 KVO1 KQ LOV1 M2 E- CT F6 D596 A EN ON&&TTJ CVO1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

557 ug/kg

TOXIC EFFECTS :

Blood - leukopenia Skin and Appendages - hair

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

305 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 :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

355 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 - rat

DOSE/DURATION :

37 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 :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

423 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 :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2700 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 :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

324 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 :

9500 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

500 ug/kg

TOXIC EFFECTS :

Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

4300 ug/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 :

3 mg/kg/15D-I

TOXIC EFFECTS :

Gastrointestinal - other changes Blood - leukopenia Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

500 ug/kg/5D-I

TOXIC EFFECTS :

Gastrointestinal - ulceration or bleeding from stomach Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

125 ug/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

125 ug/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

350 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - musculoskeletal system

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 - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

50 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 :

350 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 :

Subcutaneous

DOSE :

10 mg/kg

SEX/DURATION :

female 11-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

500 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

1 mg/kg

SEX/DURATION :

female 1 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - other effects to embryo

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

Sperm Morphology

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Sperm Morphology

MUTATION DATA

TEST SYSTEM :

Rodent - hamster

DOSE/DURATION :

24 ug/kg

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 327,237,1995 *** 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: 26,349,1981 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: 26,349,1981 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: 7,371,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 83934 No. of Facilities: 33 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 1386 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 83934 No. of Facilities: 273 (estimated) No. of Industries: 1 No. of Occupations: 6 No. of Employees: 14022 (estimated) No. of Female Employees: 10067 (estimated)