In vitro and in vivo antitumor effect of 5‐FU combined with piplartine and piperine

Abstract

It has been reported that piplartine and piperine, alkaloid/amide compounds from Piper species, show antitumor activities. In the present paper, the effects of the combination of 5-fluorouracil (5-FU) with piplartine or piperine was determined using in vitro and in vivo experimental models. Hematological and biochemical analyses, as well as histopathological and morphological analyses of the tumor and the organs, including liver, spleen and kidney, were performed in order to evaluate the toxicological aspects associated with different treatments. The incubation of tumor cell lines with 5-FU in the presence of piplartine or piperine produced an increase in growth inhibition, as observed by lower IC50 values for 5-FU. These effects were also observed in vivo, where the combination with piplartine but not piperine with 5-FU led to a higher tumor growth inhibition. The results indicated that either piplartine- or 5-FU-treated animals showed a low inhibition rate when they were used individually at low doses of 28.67% and 47.71%, respectively, but when they were combined at the same dose, the inhibition rate increased significantly to 68.04%. The histopathological analysis showed that the livers and the kidneys of treated animals were only slightly and reversibly affected. Neither the enzymatic activity of transaminases nor the urea levels were significantly modified when compared with the control group. Hematological analysis showed leukopenia after 5-FU treatment, which was reversed by the combined use of piplartine and piperine. These findings indicate that piplartine may enhance the therapeutic effectiveness of chemotherapeutic drugs, and moreover, this combination could improve immunocompetence hampered by 5-FU.

In vitroandin vivoanticancer properties of cucurbitacin isolated fromCayaponia racemosa

“…In association with docetaxel, cucurbitacin B also d antitumor effects in the Hep-2 (laryngeal cancer) xenograft model (Liu et al, 2008). Because such combined biological therapies hold promise for controlling tumor proliferation and drug-resistance, the development of combination chemotherapies is expected to increase the response rate and the frequency of long-term survival (Bezerra et al, 2008).…”

Enhancing Activity of Anticancer Drugs in Multidrug Resistant Tumors by Modulating P-Glycoprotein through Dietary Nutraceuticals

“…Piperine is the major plant alkaloids present in black pepper (Piper nigrum Linn) (Han et al, 2008;Do et al, 2013;Singh et al, 2013) and long pepper (Piper longum Linn) (Bezerra et al, 2008). Black pepper is one of the most common spice consumed by a large number of populations worldwide.…”

Synergistic anticancer effects of valproic acid, atorvastatin and pioglitazone in human malignant and murine cells

“…-1 ] × 100, where A is the average weight of the negative control group and B is the average tumor weight of the treated group (Bezerra et al, 2008).…”