Activity of RA-700, a cyclic hexapeptide from Rubiae Radix, in the human tumor clonogenic assay

Abstract

In vitro phase II study of a new cyclic hexapeptide anticancer agent, RA-700 was studied on the human tumor clonogenic assay. From the results of the study using the human tumor cell line of lung cancer (PC-6), RA-700 appears to possess time-dependent antitumor activity. Therefore, against the 148 human specimens of various malignancies, the chemosensitivity of RA-700 was tested at the concentrations of 10 μg/ml, 1 μg/ml and 0.1 μg/ml in continuous exposure schedule for 2 weeks by using the human tumor clonogenic assay. If the criteria for in vitro sensitivity was based on ≧ 70% inhibition of colony formation, out of 148 specimens 59 specimens (40%) were evaluable and the chemosensitivity rate of RA-700 were 67% (4/6), 22% (2/9), 17% (3/18) and 10% (1/10) for ovarian cancer, non-small cell lung cancer, breast cancer and colorectal cancer, respectively. An overall chemosensitivity rate against 13 different histologic types of cancers was 22% (13/59) (≧ 70% inhibition of colony formation) and 39% (23/59) (≧ 50% inhibition of colony formation). RA-700 showed almost same chemosensitivity compared to that of five standard anticancer drugs (adriamycin, mitomycin C, cisplatin, vinblastine and 5-FU), but the spectrum of RA-700 activity appears to be different from that of the standard drugs. Furthermore, the antitumor activity of RA-700 had no relationship with prior chemotherapy. These results indicated that RA-700 is a candidate for phase I study.