Abstract
Tenacissoside C, a natural bioactive compound of C21 steroidal
saponins, was isolated and purified from air-dried stems of Marsdenia
tenacissima. In the present study, the MTT assay showed that
tenacissoside C exhibited obvious cytotoxicity in K562 cells with
IC50 values of 31.4, 22.2, and 15.1 µM for 24, 48, and 72 h,
respectively. Flow cytometry analysis indicated that the antiproliferative
activity induced by tenacissoside C might be executed via G0/G1 cell cycle
arrest and proapoptosis in K562 cells. Western blotting analysis elucidated
that: A) Tenacissoside C induced K562 cell cycle (G0/G1) arrest via
downregulating cycline D1 protein expression; and B) Tenacissoside C induced
K562 cell apoptosis via the mitochondrial pathway by downregulating Bcl-2
and Bcl-xL protein expression, upregulating Bax and Bak protein expression,
and activating caspase-9 and caspase-3. In vivo, significant tumor
growth inhibition activity of tenacissoside C was observed in K562
cell-bearing nude mice, accompanied by a significant antiangiogenic effect
in vivo against K562 cells (a marked decrease in MVD) and
associated with enhanced apoptotic cell death (TUNEL staining assay in
vivo), both in dose-dependent manners. The treatment with
tenacissoside C did not significantly affect body mass and macroscopic
examination of the organs in this mouse tumor model.
Key words
Marsdenia tenacissima
- Asclepiadaceae - tenacissoside C - antitumor - cytotoxicity - K562 cell - apoptosis
