Cytotoxic, antitumour and antimetastatic activity of two new polyacetylenes isolated from Vernonia scorpioides (Lam.) Pers.

Vernonia scorpioides (Lam.) Pers., popularly known as Enxuga, Erva-de-São Simão and Piracá, has been used in folk medicine for its anti-inflammatory, wound healing and antimicrobial properties. Two polyacetylenes, 5-octa-2,4,6-triynyl-furan-2(5H)-one (1) and 8'-hydroxy 3-4 dihydrovernoniyne (2), were isolated from the dichloromethane extract fraction of V. scorpioides. In this study, polyacetylene 1 demonstrated a more potent cytotoxic activity than 2 in the tumour cell lines examined, and cytotoxicity was found to be comparable to a commercial drug (p > 0.05) in melanoma cells. No significant cytotoxic effect was observed in normal cell lines. Furthermore, polyacetylene 1 induced an in vitro increase in caspase-3 activity in B16F10 cells. When polyacetylene 1 was administered intraperitoneally (i.p.) in mice, a reduction in solid tumour volume and metastasis was observed in mice injected with B16F10 cells. An increase in locomotor activity was also observed in mice with solid tumours, and an inhibition of mechanical hypersensitivity was observed in a mouse model of metastasis. Notably, no significant morphological change was observed in several organs harvested from the treated mice. In conclusion, in vitro and in vivo anticancer activity of polyacetylene 1 was consistently observed and involved the induction of apoptosis by the activation of caspase-3. The anticancer activity demonstrated by polyacetylene 1, together with the absence of preliminary toxicological effects, represents a new and interesting option for the management of neoplastic disease.