Antibacterial and Antiinflammatory Kinetics of Curcumin as a Potential Antimucositis Agent in Cancer Patients

Abstract

The antiinflammatory agent curcumin (diferuloylmethane) has a potential to mitigate cancer therapy-induced mucositis. We assessed the in vitro extent of its bactericidal activity and determined the kinetics of its antiinflammatory effect on pharyngeal cells. Bactericidal activity was assessed using the LIVE/DEAD® Kit after 4 h of exposure to curcumin (50-200 μM) in 18 oropharyngeal species commonly associated with bacteremia in febrile neutropenia. Moraxella catarrhalis or its outer membrane vesicles were used to determine the inhibitory effect of curcumin on bacteria-induced proinflammatory activity as determined by cytokine release into the supernatant of Detroit 562 pharyngeal cells using the Luminex® xMAP® technology. Curcumin exerted a concentration-dependent bactericidal effect on all 18 species tested. After 4 h at 200 μM, 12 species tested were completely killed. Preincubation of Detroit cells with 200 μM curcumin for 5 to 60 min resulted in complete suppression of the release of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, granulocyte macrophage-colony stimulating factor, and vascular endothelial growth factor. Fibroblast growth factor-2 and interferon-γ were not affected. Repetitive exposure to curcumin resulted in repetitive suppression of cytokine/chemokine expression lasting from 4 to 6 h. Through reduction of oral microbial density as well as suppression of inflammation cascades curcumin may prevent cancer therapy-induced oral mucositis, e.g., when applied as multiple daily mouth washes.

The Indian Spice Turmeric Delays and Mitigates Radiation-Induced Oral Mucositis in Patients Undergoing Treatment for Head and Neck Cancer

“…37 Histopathological observations indicate that in the cohorts where turmeric was applied, increased levels of reepithelialization of epidermis; migration of myofibroblasts, fibroblasts, and macrophages to the wound bed; promotion of neovascularization and greater deposition of collagen was pronounced and that this effect was mediated by increased levels of transforming growth factor-β1. 37 Additionally, studies have also shown that turmeric and its principal compound curcumin possess antiinflammatory 66 effects, promote reepithelialization, 67 and enhance healing of wounds created in skin exposed to radiation. [36][37][38][39] In lieu of all these observations it can be postulated that the beneficial effects of turmeric in preventing radiation-induced mucositis can be best explained by its antiinflammatory, antioxidant, antimicrobial, modulating cytokines, and by enhancing wound healing process.…”

A Comparative Study to Assess the Effectiveness of Turmeric Mouth Wash versus Saline Mouth Wash on Treatment Induced Oral Mucositis (Tiom) in a Selected Hospital at Mangalore

“…Among patients undergoing head and neck radiotherapy, pain and decreased oral function may persist long after the conclusion of therapy. Fractionated radiation dosage increases the risk of mucositis to >70% of patients in most trials [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

Synthetic versus natural curcumin: bioequivalence in an in vitro oral mucositis model

“…Clinical isolates included Moraxella catarrhalis ATCC 25238 [4], M. catarrhalis O35E [6], Streptococcus pneumoniae serotype 6B [5] and nontypable Haemophilus influenzae [5]. The human pharyngeal cell line Detroit 562 (ATCC CCL 138) was maintained in Eagle’s minimal essential medium (MEM, Invitrogen, Basel, Switzerland) supplemented as indicated with heat-inactivated fetal calf serum (FCS), 2 mM L-glutamine, 1 mM sodium pyruvate (Sigma, St. Louis, MO), 1x nonessential amino acids (Sigma), 100 U/ml penicillin, and 100 μg/ml streptomycin at 37°C in an atmosphere containing 5% CO 2 .…”

“…Interleukin (IL)-8 was determined using a commercially available ELISA kit according to the manufacturer’s protocol (R&D Systems, Minneapolis, MN). For determination of additional cytokines and chemokines in the same cell supernatants the Luminex® xMAP® technology was used [5]. Milliplex map kits (Milliplex Corporation) were used for microsphere-based multiplex immunoassays.…”

“…To compare a synthetically manufactured high purity curcumin (sCUR) to a standard nCUR, we used our previously established in vitro mucositis system [4,5] and tested cytotoxic, anti-inflammatory, and antimicrobial properties of both substances to determine how effective the > 99% pure sCUR acts in comparison with standard nCUR. sCUR could possibly serve as a topical agent against cancer therapy-induced and other forms of oral mucositis.…”