Thus, the present study aimed to evaluate the anti-neoplastic effects of two different fractions obtained from a hydroethanolic extract of U. tomentosa: one R428 composed roughly of pentacyclic oxindole alkaloids and triterpene glycosides, and the other composed of most of the substances other than alkaloids present in the original extract, namely, phenolic glycosides and other antioxidant substances. Additionally, we compared the effects of both fractions to those of the original hydroethanolic extract. The chosen in vivo tumour model was the Walker-256 carcinosarcoma in rats, which was the same model used in our previous experiments. Currently, considerable attention is being granted to its anti-neoplastic potential as well. Various preparation methods and administration regimes have been tested against tumour lineages in vitro and in vivo, with promising results. Our current efforts follow the wake of some investigators, that experimented with fractions and isolated compounds of U. tomentosa extracts with the aim to attribute the observed pharmacological activities to a specific substance or group of substances. Nowadays, it is known that Uncaria tomentosa accumulates alkaloids, triterpenes and other classes of compounds, including phenolic glycosides, flavonoids and proanthocyanidins. Among the most abundant alkaloids found in this plant, there is a mixture of pentacyclic oxindole stereoisomers that differ in configuration at chiral centres in the positions 3, 7, 15, 19 and 20. In attempting to explain the anti-neoplastic effects of U. tomentosa, researchers have demonstrated interest in this group of substances, based on previous observations that gave them credit for its anti-inflammatory activity. However, it is important not to overlook the fact that cancer is a vast group of diseases that may vary substantially among them. Hence, the number of LY2109761 possible clinical scenarios is equally diverse, with different outcomes among tumour lineages, individuals affected, and even throughout the various locales affected by the neoplastic process in each individual. Pilarski and colleagues demonstrated awareness of this wide range of possible deviations by cross-testing extracts of U. tomentosa of different alkaloid content against several tumour lineages, both in vivo and in vitro. Interestingly, their results suggest that preparations with greater alkaloid concentrations do not necessarily achieve the best anti-neoplastic effects. As possible explanations for their results, the authors suggest an apparent selectivity of the fractions with higher alkaloid levels for some tumour lineages, low water solubility of isolated alkaloids and issues regarding the IC50 measures. Taking into account the previous observations of our research team, including the importance of oxidative stress in the W256 in vivo tumour model, and the relevant synergism between antioxidant and cytotoxic components in the anti-neoplastic effects of U. tomentosa, we propose yet another hypothesis: U. tomentosa fractions that are alkaloid-rich, but otherwise devoid of most other substances present in the original extract may perhaps leave out and disregard the antioxidant effects of such other substances, along with the beneficial synergic effects that they could be providing.