**5. Antineoplasic activity of the plant material obtained by biotechnological cultures**

From the callus culture of *Eriobotrya japonica*, nine triterpenes (ursolic acid; oleanolic acid; maslinic acid; tormentic acid; 2α,19α-dihydroxy-3-oxo-urs-12-en-28 oic acid; 2α-hydroxyursolic acid; hyptadienic acid, and the mixture of 3-O-*cis-*pcoumaroyl tormentic acid and 3-O-*trans*-p-coumaroyl tormentic acid) were isolated. The main triterpenes of the callus tissues were tormentic acid (50 mg/g DW) and 2α,19α-dihydroxy-3-oxo-urs-12-en-28-oic acid (11.8 mg/g DW), the latter compound (2a,19α-dihydroxy-3-oxo-urs-12-en-28-oic acid) is known as a potent protease inhibitor of the human immunodeficiency virus. All these triterpenes were tested in two cell lines (HSC-2 and HSC); seven of the nine triterpenes were active. Showing mean cytotoxic concentration (CC50) between 10 and 48 μg/ml, while the oleanolic acid and 2α,19α-dihydroxy-3-oxo-urs-12-en-28-oic acid exhibited weak cytotoxic activity. Additionally, the authors evaluated the *in vivo* antitumor activity of the 2α,19αdihydroxy-3-oxo-urs-12-en-28-oic acid in female ICR mouse skin (*n* = 15) during two stages of carcinogenesis; in this assay, carcinogenesis was induced topically with (+)- (E)-4-methyl 2[(E)-hydroxyimino]-5-Nitro-6-methoxy-3-hexenamide (NOR1) at a dose of 90 μg/0.1 mL of acetone. One week after NOR1 administration started, TPA (1 μg/0.1 mL of acetone) was administered twice weekly, yielding as a result a weak inhibition of the carcinogenesis. On the other hand, the authors mention that 2α,19αdihydroxy-3-oxo-urs-12-en-28-oic acid is an antiproliferative agent and that the number of papillomas diminished by 40% in 20 weeks, indicating that this compound possesses potential for the delay of carcinogen in mouse skin [142].
