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Bailey, Kathryn A.,Smith, Allan H.,Tokar, Erik J.,Graziano, Joseph H.,Kim, Kyoung-Woong,Navasumrit, Panida,Ruchirawat, Mathuros,Thiantanawat, Apinya,Suk, William A.,Fry, Rebecca C. U.S. Dept. of Health, Education, and Welfare, Publ 2016 Environmental health perspectives Vol.124 No.2
<P><B>Background</B></P><P>Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer.</P><P><B>Objectives</B></P><P>This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure.</P><P><B>Discussion</B></P><P>Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects.</P><P><B>Conclusions</B></P><P>Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes.</P><P><B>Citation</B></P><P>Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360</P>
Moolmuang, Benchamart,Singhirunnusorn, Pattama,Ruchirawat, Mathuros Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3
Cellular senescence, a barrier to tumorigenesis, controls aberrant proliferation of cells. We here aimed to investigate cellular senescence in immortalized cholangiocyte and cholangiocarcinoma cell lines using five different inducing agents: 5-aza-2'deoxycytidine, bromodeoxyuridine, interferons ($IFN{\beta}$ and $IFN{\gamma}$), and hydrogen peroxide. We analyzed senescence characteristics, colony formation ability, expression of genes involved in cell cycling and interferon signaling pathways, and protein levels. Treatment with all five agents decreased cell proliferation and induced cellular senescence in immortalized cholangiocyte and cholangiocarcinoma cell lines with different degrees of growth-inhibitory effects depending on cell type and origin. Bromodeoxyuridine gave the strongest stimulus to inhibit growth and induce senescence in most cell lines tested. Expression of p21 and interferon related genes was upregulated in most conditions. The fact that bromodeoxyuridine had the strongest effects on growth inhibition and senescence induction implies that senescence in cholangiocarcinoma cells is likely controlled by DNA damage response pathways relating to the p53/p21 signaling. In addition, interferon signaling pathways may partly regulate this mechanism in cholangiocarcinoma cells.
Ratchanok Pingaew,Supaluk Prachayasittikul,Somsak Ruchirawat,Virapong Prachayasittikul 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6
Tungstosilicic acid hydrate was employed as an efficient catalyst for the synthesis of bisindolylmethanes 4 using the Friedel-Crafts reaction of N-sulfonyl tryptamine 5 with various aromatic aldehydes, except 3-formylindole. In the excluding case, tris-indolylmethane 7 was formed via a sequential addition-elimination-addition process. The bioactivity test revealed that the phenolic hydroxyl group plays an important role in cytotoxicity; it demonstrated that ortho- and para-hydroxy bis-indolylmethane (BIM) analogs (4b and 4d) displayed cytotoxic potency toward HepG2 (human hepatocellular liver carcinoma cell line) and MOLT-3 (human lymphoblastic leukemia cell line) cancer cell lines. Significantly, both analogs showed slightly higher inhibitory efficacy than the control drug, etoposide, in HepG2 cells, and the analog 4d exhibited the most potent activity against MOLT-3 cell lines, with an IC50 value of 1.62 μg/mL.
Pattama Singhirunnusorn,Benchamart Moolmuang,Mathuros Ruchirawat 한국식품과학회 2023 Food Science and Biotechnology Vol.32 No.13
Nasopharyngeal carcinoma (NPC), a malignancy of the nasopharynx, is prevalent in Southeast Asia and Southern China. The prognosis of NPC is poor and local recurrence and metastasis often occur. Capsaicin (tran-8-methyl-N-vanillyl-6-nonenamide), a pungent constituent of hot chili peppers, shows anti-cancer activities such as anti-proliferation and anti-metastasis. Currently, the role of capsaicin in cell metastasis of NPC is not well understood. We tested whether capsaicin has anti-metastatic activity in NPC cell lines. Capsaicin suppressed cell proliferation in dose-dependent manner. Moreover, capsaicin inhibited cell metastasis as shown by wound healing assay and decreased the expressions of MMP-2 and MMP-9. In addition, the phosphorylation of mTOR was downregulated by capsaicin. Combination of capsaicin and rapamycin (mTOR inhibitor) treatments led to increasing of anti-growth and anti-metastatic activities. Therefore, capsaicin has potential to be used as an optional therapeutic drug for treatment of NPC.
Synthesis, cytotoxicity and QSAR study of N-tosyl-1,2,3,4- tetrahydroisoquinoline derivatives
Ratchanok Pingaew,Apilak Worachartcheewan,Chanin Nantasenamat,Supaluk Prachayasittikul,Somsak Ruchirawat,Virapong Prachayasittikul 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.9
1-Substituted-N-tosyl-1,2,3,4-tetrahydroisoquinolineanalogs (4a–4l) were synthesized using the modifiedPictet–Spengler reaction and evaluated for cytotoxicity. Alltetrahydroisoquinolines displayed cytotoxicity againstMOLT-3 cell lines, except for p-methoxy analog 4d. Interestingly,the o-hydroxy derivative 4k was shown to be themost potent cytotoxic againstHuCCA-1, A-549 andMOLT-3cell lines. The lowest IC50 value of 1.23 lMwas observed forMOLT-3 cells. Trimethoxy analog 4f exerted the most potentactivity against HepG2 with an IC50 of 22.70 lM, which islower than the reference drug, etoposide. QSAR studiesshowed that total symmetry index (Gu), 3D-MoRSE (Mor31vand Mor32u) and 3D Petitjean index (PJI3) were the mostimportant descriptors accounting for the observed cytotoxicities. The most potent cytotoxic compound (4k) againstMOLT-3 had the highest Gu value, correspondingly theinactive p-methoxy analog (4d) had the lowest Gu value. Onthe other hand, the highest molecular mass compound (4f)was shown to be the most potent cytotoxic against HepG2cells. The studies disclose that tetrahydroisoquinolines 4f and4k are potentially interesting lead pharmacophores thatshould be further explored. The QSAR models providedinsights into the physicochemical properties of the investigatedcompounds.