Paclitaxel

Biological Activity

Paclitaxel (Taxol) is a potent anti-neoplastic and anti-mitotic taxane compound used in cancer chemotherapy. Paclitaxel binds to the N-terminus of β-tubulin and and stabilizes microtubules arresting the cell cycle at the G2/M phase. The microtubule damage induces apoptosis through a JNK-dependent pathway followed by a JNK-independent pathway, perhaps related to the activation of protein kinase A (PKA) or of Raf-1 kinase, resulting in phosphorylation of Bcl-2. Paclitaxel stabilizes microtubules and as a result, interferes with the normal breakdown of microtubules during cell division. The ability of paclitaxel to inhibit spindle function is generally attributed to its suppression of microtubule dynamics, but recent studies have demonstrated that suppression of dynamics occurs at concentrations lower than those needed to block mitosis. At the higher therapeutic concentrations, paclitaxel appears to suppress microtubule detachment from centrosomes, a process normally activated during mitosis. The binding site for paclitaxel has been identified on the beta-tubulin subunit. In vitro and in vivo studies have demonstrated that paclitaxel is extensively metabolised by the liver to 3 primary metabolites.

Product Citations

• 

  Drug Deliv. 2021 Dec;28(1):2256-2267.

  GLUT1 targeting and hypoxia-activating polymer-drug conjugate-based micelle for tumor chemo-thermal therapy
  Paclitaxel purchased from AbMole

• 

  Transl Lung Cancer Res. 2021 Feb;10(2):1007-1019.

  Triptolide inhibits epithelial-mesenchymal transition phenotype through the p70S6k/GSK3/β-catenin signaling pathway in taxol-resistant human lung adenocarcinoma
  Paclitaxel purchased from AbMole

• 

  Chem Pharm Bull (Tokyo). 2021;69(4):325-332.

  MiR-509-3p Induces Apoptosis and Affects the Chemosensitivity of Cervical Cancer Cells by Targeting the RAC1/PAK1/LIMK1/Cofilin Pathway
  Paclitaxel purchased from AbMole

• 

  Oncogene. 2020 Sep;39(37):6024-6040.

  CRMP2 is a therapeutic target that suppresses the aggressiveness of breast cancer cells by stabilizing RECK
  Paclitaxel purchased from AbMole

• 

  Cell Cycle. 2018;17(10):1235-1244.

  Apatinib, a novel tyrosine kinase inhibitor, suppresses tumor growth in cervical cancer and synergizes with Paclitaxel.
  Paclitaxel purchased from AbMole

• 

  Cancer Biol Ther. 2018 Feb 5.

  Buformin suppresses proliferation and invasion via AMPK/S6 pathway in cervical cancer and synergizes with paclitaxel
  Paclitaxel purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Cell Cycle (2018 Jul). Figure 6. Paclitaxel (Abmole Bioscience)
	Method	Tumor xenografts growth assay
	Cell Lines	mice
	Concentrations	150 mg/kg/day
	Incubation Time	days 1 to 14
	Results	Apatinib or Paclitaxel significantly suppressed the growth of SiHa xenografts, and the combination with the 2 drugs further augmented this effect

	Source	Customer experimental result (2018 Aug). Figure 1. Paclitaxel (Abmole)
	Method	apoptosis assay
	Cell Lines	MDA-MB-231 cells
	Concentrations	2μM
	Incubation Time	24 hours
	Results	MDA-MB-231 cells were treated by paclitaxel (2μM) for 24 hours, obvious apoptosis was observed compared with the negative group.

	Source	Cancer Biol Ther (2018). Figure 7. Paclitaxel (Abmole Bioscience, Shanghai, China)
	Method	intraperitoneal injection
	Cell Lines	female Balb/c nude mice
	Concentrations	15 mg/kg/twice a week
	Incubation Time	10 days
	Results	As the growth curve demonstrates, compared to the control group, tumor growth was significantly suppressed in both the buformin and paclitaxel groups.

	Source	Cancer Biol Ther (2018). Figure 6. Paclitaxel (Abmole Bioscience, Shanghai, China)
	Method	Buformin synergizes with chemotherapy
	Cell Lines	C33A cells
	Concentrations	1 μM
	Incubation Time
	Results	In C33A cells, low-dose buformin (1μM) significantly enhanced the anti-proliferative effects when combined with cisplatin, paclitaxel, or 5-FU

	Source	J Control Release (2015). Figure 7. Paclitaxel
	Method	Viability assays
	Cell Lines	PC-3 cells
	Concentrations	5 μM
	Incubation Time	24 h
	Results	PtX from the medium caused the cells to eventually lose their elongated, branched shape and become spherical before they started dissociating and dying.

	Source	J Control Release (2015). Figure 5. Paclitaxel
	Method	Measurement of EV-bound Paclitaxel
	Cell Lines	PCa cells
	Concentrations	5 μM
	Incubation Time	24 and 48 h
	Results	The cytotoxic effect of the PtX-EVs on autologous PCa cells was compared to the free drug by viability assays. Cell viability curves were established as a function of PtX-EV dose for both PC-3 and LNCaP cells

Protocol

Cell Experiment
Cell lines	human neonatal dermal microvascular ECs (HMVECs), human umbilical vein ECs (HUVECs), human umbilical artery ECs (HUAVECs), normal human astrocytes (NHAs), normal human dermal fibroblasts (NHDFs), normal human epidermal keratinocytes (NHEKs
Preparation method	Cells including human neonatal dermal microvascular ECs (HMVECs), human umbilical vein ECs (HUVECs), human umbilical artery ECs (HUAVECs), normal human astrocytes (NHAs), normal human dermal fibroblasts (NHDFs), normal human epidermal keratinocytes (NHEKs), human mammary epithelial cells (HMEpCs), human prostate epithelial cells (PrEpCs) and human umbilical artery smooth muscle cells (UASMCs) are cultured. Cell proliferations are performed in 96-well plates using cells between passages 6 and 12. Cells are seeded at 3000–5000 cells/well and allowed to attach for 4 hours. Paclitaxel, diluted in culture medium, is added in quadruplicate wells and the cells ae incubated for 3 days before MTS reagents are added to quantitate the live cells in each well.
Concentrations	0.1-100 pM
Incubation time	72 h

Animal Experiment
Animal models	nude athymic mice with BC-V and BC-ER tumors
Formulation	Dissolved in absolute ethanol with an equal volume of cremophor and diluted 1:4 with sterile physiological saline before use
Dosages	20 mg/kg
Administration	i.v.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

[1] Peltier S, et al. Pharm Res. Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded lipid nanocapsules.

[2] Liebmann JE, et al. Br J Cancer. Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines.

[3] Sonnichsen DS, et al. Clin Pharmacokinet. Clinical pharmacokinetics of paclitaxel.