BCH3021 Lecture Notes - Lecture 6: Taxus Brevifolia, Focal Adhesion, Paclitaxel
Lecture 6 – Cytoskeletal Dynamics and Cancer: Metastasis, Cytoskeletal-
directed Treatments of Cancer
1. Microtubule targeting agents – TBAs
• Inhibitors of microtubule dynamics during mitosis
o Cancer cells can alter mutations
o Stop cell from proliferating
• Tubulin-binding agents – TBAs
• Microtubule – stabilisizing
o Taxanes (taxol, placitaxol) and epothilones (chemicals)
▪ Taxol: (pacific yew tree)
• Binds and stabilized microtubules
• Expensive to obtain
o Binds and stabilized microtubules
• Microtubule – destabilising
o Vincristin, vinblastine, vinoerlbine
o Binds subunits and prevents polymerization
• These eventually kill dividing cells, efficient against various types of
tumour cells in a human cancer patient
• Tubulin targeting Agents (TBAs)
o Bind to beta-tubulin
o Suppress spindle microtubule dynamics
o Extended mitotic arrest leads to cell death
o Freeze dividing cell →
o 8 different isomers of beta tubule →
o TUBB3 – increases resistance: doesn’t bind taxol very well
o Inhibitors of microtubule dynamics during mitosis
2. Actin Polymerization/turnover in Cells
• Cell movement and focal adhesion
o Rearranging actin cytoskeleton
o Cofilin: stabilising protein that
stabilises actin
o Capping protein
o Arp2/3 – helps branch actin
▪ Signalling pathways
can upregulate increase
concentration of
branching protein
complex → promote
formation of branch
networks of actin
o Net assembly of actin
filaments at leading edge
• Picks up presence of colon cancer
• Actin polymerization stimulates
membrane protrusion – filopodia
o Puts cortex under stress
• Lamellipodium: contacts point by integrin
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