There is an increasing demand from both patients and practicing oncologists for orally formulated
chemotherapy. The present study focused on the oral formulation for natural products that may be effectively used in oncologic treatment regimens.
Tumor-bearing mice treated with intratumoral administration of aqueous
ammonium oxalate-soluble and
ethanol-insoluble derivatives of Agaricus blazei showed marked
tumor regression at doses ranging from 0.1 to 2.5 mg (p < 0.05 vs. saline control; n = 7). However,
oral administration of this same fraction, either prior to, simultaneously with, or after,
tumor cell inoculation did not result in
tumor regression (p > 0.05 vs. control). When this fraction was treated with
hydrochloric acid (
acid-treated fraction; ATF), intratumoral administration resulted in a marked regression of
tumor growth comparable to that of the
acid-untreated fraction. More importantly, parenteral administration of ATF resulted in a significantly greater regression of
tumor growth than that produced by the untreated fraction (p < 0.05 vs. untreated; n = 7). When a total of 4.5 mg of ATF was given orally at varying schedules prior to, simultaneously with, or after,
tumor inoculation, a significant regression was seen using a schedule starting 4 days prior to inoculation (p < 0.05 vs. all other treatments; n = 7). NMR and molecular analyses showed that the ATF fraction had a molecular weight of approximately 10 kDa and consisted mainly of only (1,6)-beta- D-
polyglucose. These results suggest that the
oral administration of simple
acid-treated ATF results in a remarkable
tumor regression. Thus, simple
acid hydrolysis of natural products may not only bring measurable benefits in oncological practice, but may also be a useful general formulation for natural products for oral
chemotherapy.