Cytotoxic activity of the dichloromethane fraction from Vernonia scorpioides (Lam.) Pers. (Asteraceae) against Ehrlich's tumor cells in mice

Abstract

Vernonia scorpioides has been widely used in Brazil to treat skin problems and chronic wounds, such as ulcers of the lower limbs and diabetic lesions. In the present study, we investigated the effect of a dichloromethane (DCM) fraction of V. scorpioides leaf extract on Ehrlich ascitic and solid tumor-bearing mice. The animals were treated once a day with the DCM fraction at a concentration of 5 mg/kg, administered ip during and after the development of the tumor. The lifespan, weight, number and type of leukocytes, number of tumor cells, volume of solid and ascitic tumors were measured. The development of the tumor with pre-treated tumor cells in vitro with the DCM fraction (5 mg/kg) was analyzed and the animals were sacrificed after 7 days. The DCM fraction (5 mg/kg) totally inhibited tumor development when in direct contact with tumor cells, and also ascitic tumor development with in vitro treatment or when administered ip, in loco (after 7 days). Animals treated with the DCM fraction increased their lifespan ca. 2 weeks and maintained their body weight for 30 days. When applied immediately after the inoculation of the tumor cells in vivo, it totally abolished tumor development, with tumor development only decreasing when treatment was started 3 days after the tumor challenge. These data suggest an antineoplastic activity of the fraction. Oral or ip administration of DCM fraction (5 mg/kg) for 7 days did not reduce the solid tumor volume. The cytotoxic activity described here differs from the conventional immune suppressing profile of standard chemotherapy because it increases neutrophil influx to the peritoneal cavity. These results show that, besides exhibiting a tumoricidal activity, the DCM fraction also exhibits inflammatory activity.

Cytotoxic activity of the sub-fraction 2125 from Vernonia scorpioides against Sarcoma 180 tumor cells in mice

“…The subfraction used in this experiment, SF2125, was obtained from DCM fraction, confirms the toxic properties of these compounds. In this study, we showed that the SF 2125, obtained from the chromatographic fractionation of the DCM fraction of V. scorpioides had the same activity showed by Pagno et al, 2006. Treatment with SF-2125 totally inhibited the development of the ascetic tumor S180 when in direct contact with tumor cells, as also demonstrated through in vitro intraperitoneal administration, in loco, to the ascitic tumor development.…”

“…When applied immediately after inoculation of the tumor cells in vivo, it totally abolished the tumor development, and when treatment began 3 days after the tumor challenge, the tumor development was decreased, sustaining a probable antineoplastic activity. The fact of the intravenous treatment did not reduce the ascitic tumor volume, suggest that some enzymatic route could be deactivating the systemic via, according with previous results, where mice treated by oral via with DCM fraction of V. scorpioides did not reduce Ehrlich´s ascitic or solid tumor (Pagno et al, 2006). Among the Vernonia species, some cytotoxicity has been described for isolated sesquiterpene lactones from V. cinerea (Kuo et al, 2003) and V. lasiopus (Koul et al, 2003).…”

“…We recently showed that when the tumor was developed in the ascitic form, daily intraperitoneal inoculation of DCM fraction from Vernonia scorpioides extract led to an increase in peritoneal leukocytes, and the tumor did not grow, increasing the animals' lifespan and maintaining the body weight during the 30 days of treatment. (Pagno et al, 2006). These results show that besides tumoricide effects, DCM fraction also has inflammatory activity.…”

“…In our previous work we investigated the effect of the dichloromethane fraction (DCM) from the crude extract on Ehrlich ascitic and solid tumors in mice. Dichloromethane fraction showed high cytotoxicity against tumor cells, especially when applied in loco to the tumor development (Pagno et al, 2006). This promising antitumoral result obtained with the DCM fraction led us to partition it, in order to obtain fractions of increasing polarity and the ethyl acetate sub-fraction (SF 2125) showed the highest cytotoxicity against Sarcoma 180 ascitic tumor cells when applied in loco to the tumor development.…”

Effects of the topical application of an ethyl acetate fraction from Vernonia scorpioides on excisional wounds infected with Staphylococcus aureus in rats

“…Previous studies of V. scorpioides crude extract and its derived chloroform and hexane fractions have shown fungicide and moderate bactericide activity (Freire et al, 1996), and its use as a treatment for mange (scabies) has been recorded (Lans et al, 2001). In mice, the dichloromethane fraction (5 mg/kg) from the crude extract totally inhibited tumor development (Pagno et al, 2006), while subfraction 2125 from the crude extract (5mg/kg) inhibited tumor growth in the Sarcoma 180 ascitic tumor model in mice (Kreuger et al, 2009). The topical use of its alcoholic extract (200 mg of the V. scorpioides hydrogel) showed mild wound healing effects in rats when the wounds were treated topically for 30 days (Leite et al, 2002), although noninfected skin ulcers treated with an ointment 20% of the crude concentrated extract from V. scorpioides with solid Vaseline and lanoline (1:2) showed toxicity for the tissues when applied immediately after the incision in mice.…”