Solenostemma argel Hayne (Asclepiadaceae) is an Egyptian plant whose leaves are commonly used in traditional medicine as a purgative, antipyretic and antispasmodic remedy. From the pericarps, hairy seeds and leaves fifteen new 14,15-secopregnane glycosides, namely argelosides A-J, and nine new 15-ketopregnane glycosides, namely stemmosides C-K, have been isolated. Argelosides A-J show very unusual structures characterized by the opening of ring D between C-14 and C-15, and the occurrence of two ketal functions on C-14 and C-20 generating three five-membered rings with oxygenated functions in positions 16 and 15, respectively. Stemmosides D-J are characterized by the occurrence of an uncommon 14β proton configuration while stemmosides E and F possess in addition a rare enolic function in C-16. Apparently these compounds are the first pregnanes isolated from plants known to have a 15 keto, cis CD ring junction. On the other hand, stemmosides C, D and G-K are the only natural compounds which display an unusual C-17α side chain and no substitution in C-12. On the basis of antitumor and cytotoxic activities reported for pregnane and their glycosides and considering the very unusual structural features of argelosides and stemmosides, the antiproliferative activity of these compounds against Kaposis sarcoma cells was evaluated. Thus a dose dependence study was performed to test the effects of compounds on the VEGF-induced KS cell proliferation in a concentration range 0.1-20 μM. Results indicated that 15-keto-pregnane glycosides and 14,15-secopregnane glycosides reduced the VEGF-induced KS cell proliferation in a dose-dependent manner and the highest reduction occurred at concentration of 10 μM.