In vitro anticancer activities of Leonurus heterophyllus sweet (Chinese motherwort herb).
OBJECTIVE
To investigate the anticancer activities of Chinese motherwort herb (Leonurus heterophyllus Sweet; LHS).


METHODS
Dried LHS was extracted and reconstituted in phosphate-buffered saline. The in vitro antiproliferation activities of the extract were tested against seven human cancer cell lines. The DNA ladder assay and cell morphologic studies were performed to verify the drug's apoptotic activities. The possible pathway by which LHS induced apoptosis was also explored by examining mitochondrial depolarization, cytochrome c release, and caspase-3 activation.


RESULTS
The LHS extract was effective in inhibiting the growth of all seven cancer cell lines tested. The IC(50) (50% inhibition concentrations, milligrams of raw material per milliliter) were in the range of 8.0-40.0 when the drug exposure time was 48 hours. The inhibitory action of the herbal extract was time- and dose-dependent. A significant decrease in activity was seen when the drug exposure time was shortened. Microscopic examination of the LN CaP and other cancer cell lines after treatment with LHS revealed morphologic changes that are typical of cells undergoing apoptosis. DNA fragmentation was obvious in the DNA latter assay and this confirmed the induction of apoptosis of the cancer cells by LHS. The mitochondria of the LHS-treated cells were found to undergo depolarization. Cytochrome c was released into the cytosol from the LHS-treated cells but not from the control cells. Cells treated with LHS showed cleavage of the full-length poly[ADP(ribose)] polymerase (PARP; 112 kd) to generate the 85-kd cleaved PARP fragment indicating the activation of caspase-3.


CONCLUSIONS
LHS was able to induce apoptosis of all the tumor cell lines tested. The antiproliferation effect was dose- and time-dependent. The mitochondrion was found to be involved in the apoptosis induced by the LHS extract.
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects; D031332:Leonurus; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic