Herbal Extract Selectively Kills Cancer Cells

An extract prepared from the traditional medical herb Anemarrhena asphodeloides induces cell death (apoptosis) in cancer cells but does not have this effect on normal tissues.

The drug candidate BN108, derived from A. asphodeloides, was found to cause the selective cytotoxicity of some types of cancer cell lines. BN108 has been under development by investigators at the pharmaceutical company Bionovo (Emeryville, CA, USA). In a paper published in the September 30, 2009, online edition of the journal PLoS ONE a team from Bionovo described the active component of BN108 and explained the molecular basis for its anticancer effect.

They explained that chemical fractionation of BN108 revealed that its cytotoxicity was associated with a class of steroidal saponins called timosaponins. Timosaponin BII (TBII) is a major saponin in BN108, but it showed little cytotoxicity. A much less abundant component, TAIII, induced cell death in tumor cells but not in normal cells, reproducing the selectivity of the total extract BN108. Glycosidase treatment, by removing the extra sugar moiety in TBII, converted it to TAIII and conferred cytotoxic activity.

Analysis of the mechanisms of death induced by TAIII revealed activation of two distinct proapoptotic pathways: first, inhibition of mTORC1 manifested in much reduced phosphorylation of mTORC1 targets; second, induction of endoplasmic reticulum stress. Because these drugs did not inhibit mTORC1 and caused only a slight inducement of ER stress in normal cells, they selectively killed tumor cells.

"BN108 and timosaponin AIII (TAIII) are cytotoxic towards tumor cells but significantly less to normal cells," said senior author Dr. Emma Shtivelman, director of cancer research at Bionovo. "BN108 and TAIII kill tumor cells by eliciting two responses: first, they inhibit the oncogenic pathway known as mTORC1 that is abnormally activated in many tumors. Second, they induce a profound stress in the endoplasmic reticulum of tumor cells. This dual effect of the drug on tumor cells leads to their demise. Normal cells do not have a highly active mTORC1, and TAIII has no effect on the basal activity of this pathway in noncancerous cells. Therefore, after treatment with the same dose of TAIII or BN108, tumor cells succumb to death, while normal cells survive."

Dr. Isaac Cohen, CEO of Bionovo said, "An important feature of any new anticancer therapy is the drug's selectivity toward cancer cells, which should result in low toxicity, thus allowing it to be administered for a long duration. BN108 and its active component TAIII, orally administered, have a promising future for treatment of cancer because of their apparent ability to kill cancer cells while sparing normal cells. BN108 and TAIII are part of Bionovo's broad pipeline of novel selective anticancer agents."

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