Planta Med 2007; 73(13): 1377-1383
DOI: 10.1055/s-2007-990221
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

In Vivo Antitumoral Activity of Stem Pineapple (Ananas comosus) Bromelain

Roxana Báez1 , Miriam T. P. Lopes1 , Carlos E. Salas2 , Martha Hernández3
  • 1Facultad de Ciencias Médicas, Ciego de Ávila, Cuba
  • 2Departamentos de Farmacología, Bioquímica e Imunologia, Instituto de Ciencias Biológicas, Universidade Federal Minas Gerais, Belo Horizonte, Brasil
  • 3Laboratorio de Ingeniería Metabólica, Centro de Bioplantas, Universidad de Ciego de Avila, Cuba
Further Information

Publication History

Received: June 18, 2007 Revised: July 24, 2007

Accepted: August 27, 2007

Publication Date:
24 September 2007 (eFirst)

Abstract

Stem bromelain (EC 3.4.22.32) is a major cysteine proteinase, isolated from pineapple (Ananas comosus) stem. Its main medicinal use is recognized as digestive, in vaccine formulation, antitumoral and skin debrider for the treatment of burns. To verify the identity of the principle in stem fractions responsible for the antitumoral effect, we isolated bromelain to probe its pharmacological effects. The isolated bromelain was obtained from stems of adult pineapple plants by buffered aqueous extraction and cationic chromatography. The homogeneity of bromelain was confirmed by reverse phase HPLC, SDS-PAGE and N-terminal sequencing. The in vivo antitumoral/antileukemic activity was evaluated using the following panel of tumor lines: P-388 leukemia, sarcoma (S-37), Ehrlich ascitic tumor (EAT), Lewis lung carcinoma (LLC), MB-F10 melanoma and ADC-755 mammary adenocarcinoma. Intraperitoneal administration of bromelain (1, 12.5, 25 mg/kg), began 24 h after tumor cell inoculation in experiments in which 5-fluorouracil (5-FU, 20 mg/kg) was used as positive control. The antitumoral activity was assessed by the survival increase (% survival index) following various treatments. With the exception of MB-F10 melanoma, all other tumor-bearing animals had a significantly increased survival index after bromelain treatment. The largest increase (∼318 %) was attained in mice bearing EAT ascites and receiving 12.5 mg/kg of bromelain. This antitumoral effect was superior to that of 5-FU, whose survival index was ∼263 %, relative to the untreated control. Bromelain significantly reduced the number of lung metastasis induced by LLC transplantation, as observed with 5-FU. The antitumoral activity of bromelain against S-37 and EAT, which are tumor models sensitive to immune system mediators, and the unchanged tumor progression in the metastatic model suggests that the antimetastatic action results from a mechanism independent of the primary antitumoral effect.