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  • br Prostate cancer br Prostate cancer is one of


    Prostate cancer
    Prostate cancer is one of the most common male cancers, whose symptoms are generally elusive in the initial stage. Investigation on androgen-dependent human prostate carci-noma 2-Guanidinoethylmercaptosuccinic Acid (LNCaP) found that SAMC exhibited potent ef-fects on (1) inhibition of cell growth, (2) testosterone catabo-lism rate, and (3) induction of well-known biomarkers’ ex-pression in LNCaP cells including prostate specific antigen (PSA) and prostate specific membrane antigen (PSMA) [25-27]. Furthermore, studies on androgen-independent prostate car-cinoma cell lines, including PC3, DU145 and 22Rv1, found that SAMC inhibited colony formation, increased apoptosis in vitro and suppressed CWR22R-formed xenograft tumor growth in vivo [28].
    Cancer metastasis refers to the spread of cancer cells from one organ or part of the body to another, which is the principal cause for cancer-related death. Based on colony-forming, wound-closure and Matrigel-invasion assays in potentially invasive androgen-independent prostate cancer (PCa) cells, SAMC was found to suppress PCa cell prolifera-tion and invasive abilities [29]. In a fluorescent orthotopic prostate cancer SCID mouse model constructed with a green fluorescent protein-expressing PC-3 cell line, results also indicate that SAMC could inhibit tumor growth and dissemi-nation, without obvious toxicity in vivo [30]. Further mecha-nistic investigation showed that SAMC suppressed tumor cell invasiveness by inducing E-cadherin expression and by inhibiting the activation of its transcriptional suppressor Snail [28-29]. In addition, SAMC has properties that increase the chemical sensitivity of prostate cancer cells. Docetaxel is a recently introduced new agent against hormone refractory prostate cancer (HRPC). Clinically, it has made a modest but significant improvement on patients’ survival. When applied in co-trea-tment with SAMC, the anti-cancer activities of docetaxel were significantly potentiated in in vitro assays with PC3, DU145 and 22Rv1 cells, as assessed in terms of colony form-ing inhibition, apoptosis induction and G2/M phase arrest [30].
    Breast cancer
    Breast cancer is a malignancy that commonly occurs in women with a multifactorial etiology including genetic in-heritance, obesity and hormone abnormalities. SAMC exhib-
    ited potent effects on cell growth/invasion retardation, cell cycle arrest, and apoptosis induction of both estrogen receptor (ER)-positive MCF-7 cell and ER-negative MDA-MB-231 cell. Alterations of the intrinsic apoptotic pathway, including caspase-3/9 activation, pro-apoptotic proteins (e.g. Bax, p53 and p21) up-regulation, and anti-apoptotic protein (e.g. Bcl-2 and Bcl-XL) down-regulation were the main mechanisms underlying SAMC actions [26, 33].
    Estrogen receptor (ER) is a transcription factor responsi-ble for modulating the biological activities of estrogen. Re-cently, evidence indicates that ER activity was closely related to the occurrence of breast cancer. Indeed, suppressing the activity of ER to rectify hormonal balance has been raised as a treatment option for breast cancer. Strong hydrogen bonding between Glu353/Arg394 of ER and SAMC may partially explain how SAMC inhibits ER-dependent growth of breast cancer cells [34].
    Bladder cancer
    Over-expression of inhibitor of differentiation-1 (Id-1) is often deemed a disease marker in bladder cancer for its roles in promoting neoplasm, metastasis and resistance to therapy. In a study comparing the response to SAMC by a bladder cancer cell line (RT112) with low endogenous Id-1 expression and another cell line (MGH-U1) with high endogenous Id-1 expression, it was found that Id-1 level was negatively asso-ciated with the positive effect of SAMC on cell survival. It is also worth noting that knock-down of Id-1 augments cellular susceptibility to SAMC. Overall, evidence suggests that Id-1 may be a potential target of SAMC mediated treatment of bladder cancer [7].
    Thyroid cancer
    A recent study examined the effects of SAMC on anaplastic thyroid cancer (ATC), a rare and rapidly fatal endocrine ma-lignancy [37]. The human anaplastic thyroid cancer cell line 8305C (HPACC) was subjected to SAMC challenge. In transmission electron microscopy (TEM) analysis of cellular ultrastructures, pervasive effects of SAMC were revealed, which included typical apoptotic characteristics such as cell atrophy, shrinkage, blurred contour, fragmentation and even lysis into small pieces. In cell assays, SAMC also signifi-cantly inhibited cell proliferation of HPACC-8305C, arrested the cells in G2/M phase, induced apoptosis and inhibited te-lomerase activity [37]. Nevertheless, detailed anti-cancer mechanisms of SAMC actions in thyroid cancer warrant fur-ther exploration.