In vitro and in vivo antitumor activity of Macrothelypteris torresiana and its acute/subacute oral toxicity by X.H. Huang, P.C. Xiong, C.M. Xiong, Y.L. Cai, A.H. Wei, J.P. Wang, X.F. Liang, J.L. Ruan
ABSTRACT
The aim of this study was to evaluate the antitumor potential
of Macrothelypteris torresiana by studying in vitro antitumor activity
of the protoapigenone, as well as in vivo antitumor activity and
acute/subacute oral toxicity of the total flavonoid fraction from the
roots of M. torresiana. Considering that the protoapigenone is a main
constituent of the total flavonoid fraction and it might play a key role
in the antitumor activity of M. torresiana, the MTT assay was used to
investigate the in vitro antitumor activity of the protoapigenone. Our
study revealed that the protoapigenone of M. torresiana showed
significant antitumor activity towards Hep G2, Tca-8113, MCF-7, M5 and
K562 with [IC.sub.50] values of 2.3, 0.6, 0.8, 0.3 and 0.9 [mu]g/ml,
respectively. The antitumor potential of the total flavonoid fraction
was evaluated using preparations 1, 2 and 3, which were prepared by
total flavonoid fraction directly diluted with sterile saline, dissolved
using sodium carboxymethyl cellulose (CMC-Na) and included by
hydroxypropyl-[beta]-cyclodextrin, respectively. These were investigated
in vivo using mouse sarcoma S-180 in BALB/c mice after completing tumor
inoculation for 24 h. Pronounced antitumor activity was observed in the
treated groups for preparations 2 and 3, and the high and medium doses
in particular showed very high inhibition ratio of tumor growth
(<50%). No significant difference was observed when compared to the
positive control group (5-fluorouracil). The acute/subacute oral
toxicity test was performed, and the results of acute oral toxicity
showed that the [LD.sub.50] values of preparations 2 and 3 were 2.76 and
0.87 g/kg body wt., respectively. According to the results of the
subacute oral toxicity study, the total flavonoid fraction had low
toxicity. The overall results of this study suggest that the total
flavonoid fraction from the roots of M. torresiana shows significant
antitumor activity and represents a potential source of medicine for the
treatment of cancer.
NOTE Macrothelypteris torresiana (Gaud.) Ching (Thelypteridaceae) is widely
distributed in the south of China and has been used as folk medicine
mainly for the treatment of diseases such as hydropsy and traumatic
bleeding (Institute of Botany, 1976; Ding, 1982). This recent scientific
attention was because of some unusual flavonoids isolated from the
species M. torresiana showing significant antitumor activities. Among of
them, a unique flavonoid named protoapigenone showed significant
antitumor activity against human cancer cell lines Hep G2, Hep 3B
(liver), MCF-7 (breast), A549 (lung) and MDA-MB-231 with [IC.sub.50]
values of 1.60, 0.23, 0.78, 3.88 and 0.27 ([mu]g/ml, respectively (Lin
et al., 2005).