MT L2 Mitotic spindle poisons

Question 1

What are microtubules?

Answer 1

responsible for maintaining structure of the cell and for separating sets of chromosomes during mitosis.

Interfering with formation and remodeling inhibits mitosis and therefore the proliferation of cancer cells

Question 2

microdubules are assembalies of …………

each has….

Answer 2

tubulin dimers

one alpha and one beta subunit

Question 3

how do tubulin dimers work

Answer 3

spiral strucutre onto a base plate - remodelled by the loss of pull of free tubulin dimers and growing and shrinking dynamic equillibrium,

microtubules are in dynamic equillibrium with tubulin dimers

Question 4

What do mitotic spindle poisons interfer with

Answer 4

the dynamic equillibrium of microtubules with individul tubulin dimers

Question 5

name 4 vinka alyaloids

Answer 5

vinblastine
vincristine
vindesine
Vinorelbine

Question 6

how do vinca alkyloids work (3 steps)

Answer 6

1. bind strongly to tubulin dimers causing conformatoional change and preventing binding to microtubules
2. also bind to individual tubulin dimers to stop them adding on
3. individual complexes of vinca alkyloid and tubuin dimer condense into paracrystlline aggregates - irriversible process

(le chatelier’s principle applies - microtubules shrink)

Question 7

What cancers can we use Vincristine for

Answer 7

Leukaemias
Lymphomas
Mammary carcinoma
Neuroblastoma
Rhabdomyosarcoma

Question 8

What cancers can we use Vinblastine for

Answer 8

Lymphomas
Testicular carcinomas
Ovarian carcinomas
Bladder carcinomas
Hodgkin’s lymphoma

Question 9

What cancers can we use Vindesine

Answer 9

Leukaemias

Lymphomas

Question 10

What cancers can we use Vinorelbine

Answer 10

Non-small-cell lung carcinoma

Mammary carcinoma

Question 11

additional way vinblastine works?

Answer 11

caps off the +ve end ff micro tubule, prevetting new tubulin dimers adding

Question 12

name two taxol/taxol like drugs

Answer 12

Paclitaxel (taxol)

Docetaxel (taxotere)

Question 13

What is paclitaxel used for?

Answer 13

mammary and ovarian carcinoma

Question 14

what is docetaxel used for

Answer 14

prostate
mammary
ovarian
and
lung
(all carcinomas)

Question 15

Action of taxoles

Answer 15

Taxols bind to taxol-binding sites on the inside surface of the microtubule, preventing disassembly as dimers cannot dissociate off the end.

The microtubule cannot grow/shrink therefore inappropriate microtubules remain.

Concerntration of free tubulin dimers decreases so new microtubultes cannot be formed

Question 16

name two colchicine like drugs

Answer 16

colchicine and Combretastatin A-4

Question 17

When is colchcine used

Answer 17

no currently approved for cancer

approved for gout

Question 18

when is combretastatin a-4 used

Answer 18

in clinical trials for cancer

Question 19

what is the mode of action of BOTH colchicine like drugs?

Answer 19

binds at colchicine-binding sites on b-tubulin in MICROTUBULES disfavours disassembly of inappropriate microtubules.
AND
binds to colchicine-binding sites on the b-tubulin SUBUNITS, disfavouring assembly of protofilaments.

bulkiness of the drug stops subunit binding. Fowls up assembly and stops association