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Antitumor activity of thevetoside in vitro
Objective:
To study the effects of thevetoside (TS), a cardiac glycoside, and an inhibitor of Na+, K(+)-ATPase, on tumor cells cultured in vitro.
Methods:
The cytotoxic effects of TS on tumor cells were determined by trypan blue dye exclusion, neutral red vital staining and clonogenic assay. The time-effect relationship and growth inhibition of tumor cells by TS were assayed with trypan blue exclusion method.
Results:
TS at low doses (0.005-0.1 mg.L-1), with dose dependence, was able to kill SMMC-7721, SGC-7901 and HeLa cells. IC50 values for SMMC-7721, SGC-7901 and HeLa cells were 0.007, 0.011 and 0.018 mg.L-1 by trypan blue dye exclusion test and 0.016, 0.055 and 0.078 mg.L-1 by neutral red vital staining test. TS inhibited the clonal forming rate of SMMC-7721 and SGC-7901 significantly with IC50 values of 0.021 and 0.036 mg.L-1, respectively. Only when the cells were continuously treated with TS for more than 8 hours, the drug-induced cell lethality could be displayed and strengthened quickly. The growth of tumor cells was notably inhibited after they were exposed to 0.1 microgram/ml of TS for 12 hours. All the experimental results of antitumor activity in vitro showed that SMMC-7721 was most sensitive to TS among the three kinds of tumor cells.
Conclusions:
TS has cytotoxic action on tumor cells cultured in vitro and this lethal effect must have an action process, in which tumor cells are not dead but suffer from deadly injury and lost the capability of unlimited proliferation.
Insights
Thevetoside (TS), a cardiac glycoside, exhibits cytotoxic effects on various tumor cells in vitro. This compound inhibits tumor cell proliferation, indicating potential as an anticancer agent.
Area of Science:
- Pharmacology
- Oncology
- Cell Biology
Background:
- Cardiac glycosides, such as thevetoside (TS), are known inhibitors of Na+, K(+)-ATPase.
- Tumor cells possess distinct cellular mechanisms that may be targeted by cytotoxic agents.
Purpose of the Study:
- To investigate the in vitro cytotoxic effects of thevetoside (TS) on SMMC-7721, SGC-7901, and HeLa tumor cell lines.
- To determine the dose- and time-dependent activity of TS on tumor cell viability and proliferation.
Main Methods:
- Cytotoxicity was assessed using trypan blue dye exclusion, neutral red vital staining, and clonogenic assays.
- Time-course and dose-response relationships were evaluated to establish IC50 values and growth inhibition parameters.
Main Results:
- Thevetoside demonstrated dose-dependent cytotoxicity against SMMC-7721, SGC-7901, and HeLa cells, with varying IC50 values across assays.
- Significant inhibition of clonal formation was observed for SMMC-7721 and SGC-7901 cells.
- Continuous exposure to TS for over 8 hours was required for observable and strengthening cell lethality, with notable growth inhibition at 0.1 µg/ml after 12 hours.
- SMMC-7721 cells exhibited the highest sensitivity to TS among the tested cell lines.
Conclusions:
- Thevetoside exerts a cytotoxic action on cultured tumor cells.
- TS induces a lethal injury in tumor cells, impairing their ability for unlimited proliferation, rather than immediate cell death.