Editorial [Hot Topic: Prospective Clinical Role for Anticancer Garlic Organosulfur Compounds (Guest Editor: Hassan T. Hassan)]

The reputation of garlic (Allium Sativum) as an effective remedy for tumours extends back to the Egyptian Codex Ebers of 1550 B.C. Half a century ago, Weisberger and Pensky (1958). have reported the tumour inhibitory property of a sulfhydryl-blocking agent in Garlic [1]. During the past 25 years, numerous studies of several organosulfur compounds extracted from garlic (Table 1) have demonstrated their biological effects in preventing and/or controlling cancer. Allicin is a transient compound responsible for the typical odour of garlic that readily decomposes into several organosulfur compounds. Diallyl trisulfide (DATS) is the most abundant in fresh garlic oil whereas commercial garlic oil products have primarily diallyl disulfide (DADS) [2]. However, after consumption of raw garlic, allicin is decomposed in stomach acid into several compounds mainly DADS that was also detected in human breath without other organosulfur volatiles [3,4]. Moreover, incubation with whole blood at 37°C, demonstrated longer bioavailability for DADS (Half-life, 60 min) compared with DATS (Half-life, 4 min) and ajoene (Half-life, 1 min) [3,5].

Several epidemiological studies have demonstrated the benefit of garlic consumption in reducing risk of several human malignancies including colorectal, esophageal, gastric and prostate cancer. The Iowa women's health case/control (212/3500) study has shown 48% lower risk of colon cancer for the highest intake in comparison with no intake of garlic [6]. The multicentre Italian case/control (1016/1159) study has reported 40% lower risk of stomach cancer for the highest intake of raw garlic compared to the lowest intake [7]. The Chinese case/control (152/234) study has identified protective effect of high garlic intake against esophageal cancer in a high epidemic area in the Jiangsu province [8]. The English case/control (328/328) study has established a lower risk for prostate cancer with high intake of garlic among men before the age of 75 years [9], that was confirmed in a larger European case/control (1294/1451) study [10]. The Shanghai case/control (291/414) study has found significantly decreased risk for laryngeal cancer with high garlic consumption [11].

Several bioactive garlic organosulfur components have demonstrated profound anticancer effects in preventing carcinogenesis, stopping tumour growth, inducing cancer cell death as comprehensively illustrated in this issue. The numerous in vitro cell line experiments and in vivo animal model studies reviewed in the manuscripts of this thematic issue have clearly determined the various biological and molecular mechanisms responsible for the anticancer activity of these garlic organosulfur compounds. Druesne-Pecollo and Latino-Martel provided comprehensive evidence from numerous in vitro and in vivo studies confirming the efficacy of garlic organosulfur compounds in inhibiting histone deacetylase activity in several types of tumour suggesting a prominent role in cancer control and prevention. Tsubura et al. demonstrated the various mechanisms of action of DADS in exerting anticancer activity in breast cancer cells in both in vitro and in vivo studies arguing the case for its role in the prevention and control of breast cancer. Diedrich et al. illustrated the molecular targets for the anticancer biological activity of garlic organosulfur compounds including several metabolic, transporter or repair enzymes that are pivotal for malignant cell proliferation, metastases and survival. Kaschula et al. reported the unique anticancer biological actrivity of several synthetic E- and Z-ajoene analogues in human cancer cells.

More significantly, some garlic organosulfur compounds have been shown to enhance the efficacy of several routinely used chemotherapeutic drugs against drug-resistant human malignant cells. Ajoene has been shown to enhance the efficacy of both cytarabine and fludarabine in human resistant leukaemia KG1a cells [12,13]. Also, DAS has been shown to attenuate the resistance of human leukaemia K562 cells to vinblastin and vincristine by significant reduction of p-glycoprotein-mediated multidrug resistance [14].

Two pilot clinical studies of garlic compounds have demonstrated their clinical benefits in cancer patients. The topical application of ajoene has induced significant clinical response with reduction in tumour size in 17 out of 21 patients with skin basal cell carcinoma [15]. The daily dose of 0.2g garlic extract/kg body weight for one month has significantly lowered the mass of prostate and the international prostate score values in 27 patients with benign prostate Hyperplasia as well as the total and free prostate-specific antigen (PSA) in 9 patients with prostate cancer [16].

These garlic organosulfur compounds are promising candidates for cancer treatment with proven pre-clinical anticancer biological activities through well-established molecular mechanisms and preliminary clinical efficacy in small number of patients. Further pre-clinical animal and pilot clinical studies to establish their bioavailability, pharmacokinetics and tolerance are warranted to exploit their clinical role as supplement to improve the current chemotherapy outcome in patients suffering from several human malignancies.....