Doxorubicin HCL

Biological Activity

Doxorubicin (Adriamycin) HCl is an antineoplastic agent used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. Doxorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis. Doxorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication. In studies with isolated nuclei, adriamycin was also a more potent inhibitor of DNA synthesis than RNA synthesis. However, with intact cells, adriamycin inhibited both DNA and RNA synthesis to about the same extent. The inhibition produced by adriamycin on RNA synthesis in intact cells was greater than that observed in the cell-free systems. Adriamycin inhibited protein synthesis in a cell-free system consisting of polyribosomes, transfer RNA, and enzymes but did not inhibit protein synthesis in intact cells. Combination therapy experiments with sirolimus (rapamycin) and doxorubicin have shown promise in treating Akt-positive lymphomas in mice.

Product Citations

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  Mol Med Rep. 2021 Mar;23(3):219.

  Shengxian decoction decreases doxorubicin‑induced cardiac apoptosis by regulating the TREM1/NF‑κB signaling pathway
  Doxorubicin HCL purchased from AbMole

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  2020 Aug.

  Blockage of AMPK-ULK1 pathway mediated autophagy promotes cell apoptosis to increase doxorubicin sensitivity in breast cancer (BC) cells: an in vitro study
  Doxorubicin HCL purchased from AbMole

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  PLoS One. 2017 Jul 13;12(7):e0181340.

  Development and characterization of a human three-dimensional chondrosarcoma culture for in vitro drug testing
  Doxorubicin HCL purchased from AbMole

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  Biomaterials 2012 Jun;4345-52.

  Antitumor efficacy following the intracellular and interstitial release of liposomal doxorubicin
  Doxorubicin HCL purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Ther Deliv (2015). Figure 2. Doxorubicin HCl
	Method	equilibrium dialysis
	Cell Lines	HeLa cells
	Concentrations	1 mg/ml
	Incubation Time	24 h
	Results	Similar to the effect of acyl chain length on the release rate of doxorubicin, PEGylation of the liposome tended to decrease the release rate.

	Source	Ther Deliv (2015). Figure 1. Doxorubicin HCl
	Method	WST-8 assay
	Cell Lines	HeLa cells
	Concentrations	1.0 μg/ml
	Incubation Time	24 h
	Results	Cytotoxicity and intracellular uptake of doxorubicin were not positively correlated in liposomes no. 2–5, 13–15 and 16–18.

Protocol

Cell Experiment
Cell lines	Human choriocarcinoma cell line
Preparation method	Briefly, cells were plated on 96-well plates (10,000 cells/well) and a day after (cell culture 80% confluent) were exposed to doxorubicin (0–8 mM), L-DOX (0–8 mM) or PL-DOX (0–200 mM) in non-supplemented serum-free growth medium for 4 h. After exposure, the cells were washed and further incubated for 20 h.
Concentrations	0–8 µM
Incubation time	24 h

Animal Experiment
Animal models	Male Sprague-Dawley rats
Formulation
Dosages	4 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

Cellular pharmacokinetic mechanisms of adriamycin resistance and its modulation by 20(S)-ginsenoside Rh2 in MCF-7/Adr cells.
Zhang J, et al. Br J Pharmacol. 2012 Jan;165(1):120-34. PMID: 21615726.

Design, synthesis, and preliminary evaluation of doxazolidine carbamates as prodrugs activated by carboxylesterases
David J Burkhart, et al. J Med Chem. 2006 Nov 30;49(24):7002-12. PMID: 17125253.

Screening of antioxidants from medicinal plants for cardioprotective effect against doxorubicin toxicity
Suvara K Wattanapitayakul, et al. Basic Clin Pharmacol Toxicol. 2005 Jan;96(1):80-7. PMID: 15667600.

Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells.
Momparler RL, et al. Cancer Res. 1976 Aug;36(8):2891-5. PMID: 1277199.