Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells

Our plain-English summary of Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells, by K. Pillai, A. Ehteda, J. Akhter, et al (Anti-cancer Drugs, 2014).

The study

• Authors: K. Pillai, A. Ehteda, J. Akhter, T.C. Chua, D.L. Morris
• Journal: Anti-cancer Drugs
• Published: 2014;25(2):150-60
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneum, causally related to asbestos exposure. Nonspecific symptoms with a late diagnosis results in poor survival (<1 year). Treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has improved survival in some patients (median 3-5 years). Hence, new therapies are urgently needed. MUC1 is a glycosylation-dependent protein that confers tumours with invasiveness, metastasis and chemoresistance. Bromelain (cysteine proteinase) hydrolyses glycosidic bonds. Therefore, we investigated the antitumour effect of bromelain on MUC1-expressing MPM cell lines. MUC1 expressions in cells were assessed using immunofluorescent probes with cells grown on cover slips and western blot analysis on cell lysates. The cell lines were treated with various concentrations of bromelain and after 4 and 72 h, their viability was assessed using standard sulforhodamine assays. The cells were also treated with combinations of bromelain and cytotoxic drugs (cisplatin or 5-FU) and their viability was assessed at 72 h. Finally, with western blotting, the effects of bromelain on cellular survival proteins were investigated. PET cells expressed more MUC1 compared with YOU cells. The cell viability of both PET and YOU cells was adversely affected by bromelain, with PET cells being slightly resistant. The addition of bromelain increased the cytotoxicity of cisplatin significantly in both cell lines. However, 5-FU with bromelain did not show any significant increase in cytotoxicity. Bromelain-induced cell death is by apoptosis and autophagy. Bromelain has the potential of being developed as a therapeutic agent in MPM.

In plain English

This laboratory study tested bromelain, a mixture of enzymes extracted from pineapple, on two malignant peritoneal mesothelioma cell lines, PET and YOU. It used cultured cells, not patients, and did not study asbestos exposure. Cells were treated with bromelain alone and combined with the chemotherapy drugs cisplatin or 5-FU. Bromelain reduced cell survival in both lines, more after 72 hours than after 4 hours. The concentration inhibiting half the cells at 72 hours was 35 micrograms per ml for YOU cells and 60 for PET cells. Adding 25 micrograms per ml of bromelain lowered the cisplatin concentration needed to inhibit half the cells five-fold in YOU cells and 2.4-fold in PET cells. Bromelain with 5-FU did not considerably increase cell killing. PET cells carried more of the protein MUC1 than YOU cells. The authors interpreted protein changes as cell death by apoptosis and autophagy. They concluded that bromelain, alone or with cisplatin, may be useful against this cancer if applied directly in the abdominal cavity. They noted that high bromelain levels are difficult to reach in blood.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on cancer cell lines; the journal labels it a preclinical report
• Who was studied: Two malignant peritoneal mesothelioma (MPM) cell lines, PET and YOU, taken from the authors' cell bank at the Department of Surgery, University of New South Wales, St George Hospital, Australia. MDAMB 231 breast cancer cells were also used as a comparison for MUC1 staining. No human patients were studied.
• Exposure: Bromelain alone at 5 to 400 micrograms per ml, tested at 4 and 72 hours. Bromelain at 25 to 50 micrograms per ml was also combined with cisplatin or 5-FU at 0.01 to 0.1 micromol/l for 72 hours. The text prints these units as mg/ml and mmol/l, but the figure axes show micrograms per ml and micromol/l. Asbestos exposure was not studied.
• Main results:
  • Concentration of bromelain inhibiting 50% of cells (IC50): at 4 hours, 92 (YOU) and 95 (PET) micrograms per ml. At 72 hours, 35 (YOU) and 60 (PET) micrograms per ml. The authors took this to mean YOU cells were more sensitive.
  • At 100 micrograms per ml of bromelain, 80% of cells died. At 400 micrograms per ml, 95% of YOU cells and 90% of PET cells died.
  • Cisplatin alone had an IC50 of 0.05 micromol/l in YOU cells. Adding 25 micrograms per ml of bromelain lowered this five-fold, to 0.01.
  • In PET cells, adding 25 micrograms per ml of bromelain lowered the cisplatin IC50 2.4 times; Table 3 gives 0.085 without bromelain and 0.035 with it, in micromol/l. The discussion gives this as 2.3 times.
  • 5-FU alone killed few cells: a maximum of 30% of YOU cells and under 20% of PET cells. Adding bromelain to 5-FU did not considerably increase cell killing at the concentrations tested.
  • PET cells showed more MUC1 than YOU cells, on both immunofluorescence staining and western blot.
  • In both cell lines, bromelain left caspase 3 unchanged and increased caspases 7, 8 and 9. Light chain 3B, a marker of autophagy, appeared only at 100 and 200 micrograms per ml. The authors interpreted these changes as cell death mainly through apoptosis, with autophagy also taking place.
• The authors' conclusion: The authors concluded that bromelain by itself may be used as a therapeutic agent for MPM, because the high concentrations needed can be reached by applying it locally in the peritoneal cavity. They also concluded that bromelain combined with cisplatin may serve as a useful and effective therapy. They called for further optimization studies.
• Limitations the authors state:
  • High concentrations of bromelain are difficult to achieve in blood; the authors state that levels above 10 ng/ml are not achievable.
  • Many other proteins and pathways not examined here may be affected by bromelain; this needs further investigation.
  • The study was not designed to show bromelain's specific effect on the MUC1 molecule.
  • Whether bromelain and cisplatin act synergistically or only additively was not determined.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Cisplatin, Fluorouracil (5-FU), Peritoneal Mesothelioma, Neoplasm, Peritoneum, Asbestos Exposure, Cytoreductive Surgery, HIPEC.

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