03-03-2012, 04:52 PM
Anticancer Activity of Chamaejasmine:Effect on Tubulin Protein
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Introduction
Cancer, which is a great threat to human life, is a serious disease with a complex pathogenesis.
Many chemotherapeutic drugs have been developed to treat cancer, including DNA-alkylating agents
and antimitotic agents [1,2]. A great number of natural products such as taxol and vinca alkaloids are
well known for their effective antimitotic activity. However, their complex synthesis, difficult
formulation, and lack of oral availability makes these drugs suboptimum for clinical treatment of
cancer [3]. Hence, there is considerable interest in the development of novel molecules that inhibit
tubulin polymerization.
In the past three decades, microtubules continue to be one of the most successful cancer
chemotherapeutic targets [4-8]. The taxenes and vinca alkaloids are well-characterized anti-mitotic
compounds which are widely used in clinical situations. However, the development of multidrug
resistance has limited the potency of these antimitotic compounds [9]. Therefore, there has been a great
interest in identifying novel microtubule inhibitors that can overcome various modes of resistance and
exhibit improved pharmacology profiles [10-12].
Results and Discussion
2.1. Cytotoxicity Assays
The cytotoxicity of chamaejasmine was evaluated on nine human cancer cell lines (MCF-7, A549,
SGC-7901, HCT-8, HO-4980, Hela, HepG2, PC-3 and LNCap) and two normal cell lines (Vero and
MDCK) using MTT assays. Taxol was used as positive control. The results are listed in Table 1. As
shown, chamaejasmine exhibited strong cytotoxicity against all nine cancer cell lines. Among all of
them, chamaejasmine showed more notable cytotoxicity than taxol against MCF-7, HO-4980, A549
and PC-3, with IC50 values of 4.02, 5.31, 4.84 and 2.28 μM, respectively
3. Experimental
3.1. Materials
Chamaejasmine and taxol were obtained from Sigma Chemical Co. (St. Louis, MO, USA) and were
stored in glass vials with Teflon sealed caps at −20 ± 0.5 °C in the absence of light. A 10 mM stock
solution of chamaejasmine was prepared in dimethyl sulfoxide (DMSO) and stored at −80 °C.
Deionized water was used in all experiments.
3.2. Growth of Cells
MCF-7, A549, SGC-7901, HCT-8, HO-4980, Hela, HepG2, PC-3, LNCap, Vero, MDCK cell lines
were purchased from Harbin Medical University, China. All the tumor cells were maintained in
Roswell Park Memorial Institute 1640 (RPMI 1640) medium supplemented with 10% fetal bovine
serum and 100 U/mL penicillin and 100 μg/mL streptomycin. Vero and MDCK were maintained in
DMEM medium supplemented with 10% fetal bovine serum and 100 U/mL penicillin and 100 μg/mL
streptomycin. The cells were kept at 37 °C in a humidified atmosphere containing 5% CO2.