Kyle J. Norton

Polysulfides are phytochemicals in a class of chemical compounds containing chains of sulfur atoms, belonging to the group of Organosulfides found abundantly in ioxidized product, including beer, wine, whiskey, garlic oil, etc.
1. Phytochemical Polysulfides and colon cancer
Bowel cancer also known as colorectal cancer, is defined as a condition of the abnormal proliferation of cells in the colon, rectum, or vermiform appendix. Bowl is divided in 2 parts, the first part of the bowel, the small bowl, is involved with the digestion and absorption of food. The 2nd part, the large bowel which consist the the colon and rectum, is involved in absorption of water from the small bowel contents and broken down of certain materials in the feces into substances of which some of them to be re absorbed and reused by the body. Bowel cancer is relatively very common and slowly growing and progress cancer and in predictable way.
Bowel cancer is the third most commonly diagnosed cancer in developed countries, including U>S and Canada.
According to the study of the University of the Saarland, coumarin polysulfides showed to inhibit cell growth and induce apoptosis in HCT116 colon cancer cells, through regulated the phosphatase activity of the cell cycle regulating cdc25(Cell division cycle 25, family of dual-specificity phosphatases) family members(1). Diallylsulfides, another family member of Garlic-derived organo sulphur compounds, also inhibited HCT116 human colon cancer cells, through reduced cell viability, cell cycle arrest and apoptosis(2) and colo 205 human colon cancer cells through affected resistant gene expression(3)

Reference
(1) Coumarin polysulfides inhibit cell growth and induce apoptosis in HCT116 colon cancer cells by Saidu NE1, Valente S, Bana E, Kirsch G, Bagrel D, Montenarh M.(PubMed)
(2) Diallylpolysulfides induce growth arrest and apoptosis by Busch C1, Jacob C, Anwar A, Burkholz T, Aicha Ba L, Cerella C, Diederich M, Brandt W, Wessjohann L, Montenarh M.(PubMed)
(3). Diallyl sulfide, diallyl disulfide and diallyl trisulfide affect drug resistant gene expression in colo 205 human colon cancer cells in vitro and in vivo by Lai KC1, Kuo CL, Ho HC, Yang JS, Ma CY, Lu HF, Huang HY, Chueh FS, Yu CC, Chung JG.(PubMed)

2. . Phytochemical Polysulfides and breast cancer
Breast cancer (malignant breast neoplasm) is a cancer started in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
Eating garlic daily and regularly is associated to reduced risk of cancer due to its properties in stimulated cells arrest at G2/M phase, the cells with a sub-G1 DNA content, and the cells with caspase-3 activity(1). In sensitive (MCF-7) and resistant (Vcr-R) human breast carcinoma cells , Diallyl- and dipropyltetrasulfides showed to inhibit growth of both cancer cell lines, through cell cycle arrest associated to antiproliferative effect(2). The Alexandria University study also supported the role of diallyl trisulfide in inhibition of MCF-7 breast cancer but throught enhanced the expression levels of FAS and cyclin D1, but in contrast, downregulated the expression levels of Akt and Bcl-2(3).

References
(1) Anticancer effects of diallyl trisulfide derived from garlic by Seki T1, Hosono T, Hosono-Fukao T, Inada K, Tanaka R, Ogihara J, Ariga T.(PubMed)
(1) Antiproliferative effect of natural tetrasulfides in human breast cancer cells is mediated through the inhibition of the cell division cycle 25 phosphatases by Viry E1, Anwar A, Kirsch G, Jacob C, Diederich M, Bagrel D.(PubMed)
(2) Garlic constituent diallyl trisulfide induced apoptosis in MCF7 human breast cancer cells by Malki A1, El-Saadani M, Sultan AS.(PubMed)

3. Polysulfides and skin cancer
Skin cancer is a medical condition of uncontrolled growth of abnormal skin cells and often detected at an early stage.
In skin cancer progression, diallyl trisulfide (DATS) is more potent than mono- and disulfides against skin cancer, through inhibited cell growth of human melanoma A375 cells and basal cell carcinoma (BCC) cells by increasing the levels of intracellular reactive oxygen species (ROS) and DNA damage and by inducing G2/M arrest, endoplasmic reticulum (ER) stress, and mitochondria-mediated apoptosis(1). The study by the National Taiwan University, also showed that Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), extracted from crushed garlic, inhibited skin cancer cell growth through involved in G(2)/M arrest and apoptosis via activation of p53 pathway in response to the oxidative DNA damage(2). The Chung Shan Medical University Hospital, study also insisted that DAS protect against ultraviolet B (UVB)-induced skin tumor formation through anti photocarcinogenesis effect accompanied by the down-regulation of cell-proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, and up-regulation of p53, p21/Cip1 to prevent DNA damage and facilitate DNA repair in hairless mice(3).

References
(1) Molecular mechanisms of garlic-derived allyl sulfides in the inhibition of skin cancer progression by Wang HC1, Pao J, Lin SY, Sheen LY.(PubMed)
(2) Allyl sulfides inhibit cell growth of skin cancer cells through induction of DNA damage mediated G2/M arrest and apoptosis By Wang HC1, Yang JH, Hsieh SC, Sheen LY.(PubMed)
(3) Diallyl sulfide protects against ultraviolet B-induced skin cancers in SKH-1 hairless mouse: analysis of early molecular events in carcinogenesis by Cherng JM1, Tsai KD, Perng DS, Wang JS, Wei CC, Lin JC.(PubMed)

4. Phytochemical Polysulfides and cardiovascular diseases
There are many causes of heart diseases. Most of heart diseases are caused by high blood pressure contributes to hardening of the arteries. High levels of bad cholesterol (LDL) build up in the arteries as a result of uncontrolled diet with high levels of saturated fat and trans fat. Beside cancer, heart disease kills more than 2,000 Americans everyday. Approximately 60 million Americans have heart disease.
Epidemiologic studies link intake of garlic in association to reduce risk as well as progression of cardiovascular disease(1).
According to the Institute of Preventive and Clinical Medicine, polysulfides from garlic are converted into hydrogen sulfide which has the unique property for relaxing vascular smooth muscle, inducing vasodilation of blood vessels, and significant reducing blood pressure(2), probably through its anti-apoptotic, anti-inflammatory and antioxidant effects(3). The 1Semmelweis University Institute of Human Physiology and Clinical Experimental Research, suggested that H2S as a novel gasotransmitter in the central nervous and cardiovascular systems, similarly to nitric oxide (NO) and carbon monoxide (CO), may be of value in cytoprotection during the evolution of myocardial infarction(4).

References
(1) Garlic and cardiovascular disease: a critical review by Rahman K1, Lowe GM.(PubMed)
(2) Garlic (Allium sativum L.) and cardiovascular diseases by Ginter E1, Simko V.(PubMed)
(3) Hydrogen sulfide-mediated cardioprotection: mechanisms and therapeutic potential by Lavu M1, Bhushan S, Lefer DJ.(PubMed)(4) The cardioprotective potential of hydrogen sulfide in myocardial ischemia/reperfusion injury (review) by Dongó E1, Hornyák I, Benko Z, Kiss L.(PubMed)

5. Polysulfides and Immunity
A range of sulfur-containing natural products showed to inhibit their antioxidant, antibacterial, antimicrobial, antifungal and anticancer properties, through specific chemical properties which converge in chemotypes, including polysulfides(1).
Garlic extracts and individual components, i.e., allicin, ajoen, polysulfides, essential oil, showed a significant antifungal activity, according to 1Katedra farmaceutické botaniky a ekologie Farmaceutické fakulty Univerzity Karlovy(2). Polysulfides, through its biological activity, showed effectively against candidosis in mice, according to the 1Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Japan(3).

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References
(1) A scent of therapy: pharmacological implications of natural products containing redox-active sulfur atoms by Jacob C.(PubMed)
(1) [Pharmaceutical significance of Allium sativum L. 4. Antifungal effects].[Article in Czech]by Sovová M1, Sova P.(PubMed)
(2) Optically active antifungal azoles. II. Synthesis and antifungal activity of polysulfide derivatives of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H- 1,2,4-triazol-1-yl)-2-butanol by Tasaka A1, Tamura N, Matsushita Y, Hayashi R, Okonogi K, Itoh K.(PubMed)