• Asian Pacific Journal of Cancer Prevention
• /
• 제15권17호
• /
• pp.7473-7478
• /
• 2014

Cholangiocarcinoma (CCA) is a fatal cancer with poor prognosis and less than 10% of CCA patients can be offered surgical cure. Conventional chemotherapy results in unfavorable outcomes. At present, plant-derived compounds are gaining interest as potential cancer therapeutics, particularly for treatment-refractory cancers. In this study, antitumor activity of tiliacorinine, the major alkaloid isolated from a tropical plant, on CCA was first demonstrated. Antiproliferative effects of tiliacorinine on human CCA cell lines were investigated using SRB assays. Acridine orange/ethidium bromide staining, flow cytometric analysis and DNA laddering assays were used for apoptotic determination. Apoptosis-related proteins were verified by Western blotting and antitumor activity of tiliacorinine in vivo was demonstrated in CCA xenografted mice. Tiliacorinine significantly inhibited proliferation of human CCA cell lines with $IC_{50}$ $4.5-7{\mu}M$ by inducing apoptosis through caspase activation, upregulation of BAX, and downregulation of $Bcl_{xL}$ and XIAP. Tiliacorinine considerably reduced tumor growth in CCA xenografted mice. These results demonstrated antitumor effects of tiliacorinine on human CCA in vitro and in vivo. Tiliacorinine may be an effective agent for CCA treatment.

• Archives of Pharmacal Research
• /
• 제22권2호
• /
• pp.179-183
• /
• 1999

3-Arylisoquinolin-1(2H)-ones (2) are possible bioisosteres of the $5-[4^{l}-(piperidinomethyl)phenyl]-2<$,3-dihydroimidazo[2,1-$\alpha$]isoquinoline (1) which is in clinical evaluation for the treatment of cancer. Structure-activity relationship studies of 3-arylisoquinolin-1(2H)-ones. (2) led to the synthesis of 3-arylquinolin-2(1H)-ones (3). A number of 3-phenyl substituted quinolin-2(1H)-ones were synthesized and tested for their in vitro antitumor activity against four different human tumor cell lines and 3-phenyl-N-benzyl-3,4-dihydroquinolin-2(1H)-one (12) showed the most potent activity.

• Archives of Pharmacal Research
• /
• 제25권4호
• /
• pp.416-420
• /
• 2002

A series of isoindoloquinoline derivatives was synthesized and evaluated in vitro cytotoxicity against four human cancer cell lines (HCT15, SK-OV-3, MDA-MB-468 and T-47D).

• Journal of Ginseng Research
• /
• 제40권4호
• /
• pp.400-408
• /
• 2016

Background: Ginsenoside Rh2 (GRh2) is the main bioactive component in American ginseng, a commonly used herb, and its antitumor activity had been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in HCT116 colorectal cancer cells. Methods: We examined the effect of GRh2 on HCT116 cells ex vivo. Next, we performed in vitro binding assay and in vitro kinase assay to search for the target of GRh2. Furthermore, we elucidated the underlying molecular mechanisms for the antitumor effect of GRh2 ex vivo and in vivo. Results: The results of our in vitro studies indicated that GRh2 can directly bind with PBK/TOPK and GRh2 also can directly inhibit PBK/TOPK activity. Ex vivo studies showed that GRh2 significantly induced cell death in HCT116 colorectal cancer cells. Further mechanistic study demonstrated that these compounds inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 (ERK1/2) and (H3) in HCT116 colorectal cancer cells. In vivo studies showed GRh2 inhibited the growth of xenograft tumors of HCT116 cells and inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 and histone H3. Conclusion: The results indicate that GRh2 exerts promising antitumor effect that is specific to human HCT116 colorectal cancer cells through inhibiting the activity of PBK/TOPK.

• 약학회지
• /
• 제44권4호
• /
• pp.347-353
• /
• 2000

To examine influence of artificial digestive juice on the antitumor activity of Ganoderma lucidum-A(GL-A), protein-bound polysaccharide from Ganoderma lucidum, we compared the digested protein-bound polysaccharide with undigested one both on immunopotentiating activity and influence of digestive juices. Protein-bound polysaccharide GL-B was obtained by digesting the antitumor component GL-A with artificial digestive Juices in vitro. When GL-A was administered orally to sarcoma 180 tumor-bearing ICR mice, the life prolonging effect was exhibited in a dose dependent manner Not only GL-A but GL-B increased the production of colony forming unit (CFU) to 10- and 8-fold of that of the control, respectively. Both of the protein-bound polysaccharides also showed the secretion of nitric oxide in RAW 264.7 cell lines to 3.5-and 3.7-fold of that of the control, respectively: GL-A activated components of the alternative complement pathway, whereas GL-B did not. In humoral immunity GL-A increased the activity of alkaline phosphatase in differentiated B cells to 3 times and GL-B to 4 times of that of the control. These results showed that the artificial digestive juices had no influence on the antitumor activity of the protein-bound polysaccharide from Ganoderma lucidum and that its immunomodulating activity retained after treatment with artificial digestive juice. And this provides a basis of the protein-bound polysaccharide of Ganoderma lucidum as an peroral anticancer drug.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
• /
• pp.202.1-202.1
• /
• 2001

• Archives of Pharmacal Research
• /
• 제23권5호
• /
• pp.482-487
• /
• 2000

The antitumor activity of Bifidobacterium breve K-110, and K-I11, and B. infantis K-525 was investigated. These Bifidobacterial cells and their cell wail preparations (WPG) significantly increased the survival rate of mice who had been intraperitoneally implanted with sarcoma 180 cells. Solid tumor growth was inhibited even when the sarcoma 180 cells were implanted into the groins of the mice. However, the Bifidobacterial cells did not show in vitro cytotoxicity against tumor cell lines. Cell kinetic studies revealed that these WPGs induced neutrophils, which were followed by macrophages, at the site of peritoneal injection. The WPGs directly activated these cells to inhibit the growth of tumor cells in vitro assays. Our results suggest that Bifidobacterial WPGs induce and activate nonspecific phagocytes in situ to reject growing tumor cells in the mouse peritoneal cavity.

• Environmental Analysis Health and Toxicology
• /
• 제13권3_4호
• /
• pp.87-94
• /
• 1998

The use of cisplatin is limited by severe side effects such as renal toxicity. Our platinum-base drug discovery is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogue [Pt (cis-DACH)(DPPP)]. 2NO$_3$ (PC) containing cis-1,2-diaminocyclohexane as a carrier ligand and 1,3-bis(diphenylphosphino) propane as a leaving group. Furthermore, nitrate was added to improved the solubility. In this study, its structure was determined and its antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma, and in vitro cytotoxicity was determined against primary cultured rabbit kidney proximal tubular and renal cortical cells of human kidney using colorimetric MTT assay. PC demonstrated acceptable antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma and significant activity as compared with that of cisplatin. The toxicity of PC was found quite less than that of cisplatin using MTT and $^3$H-thymidine uptake tests in rabbit proximal tubular cells and human kidney cortical cells. PC was used for human cortical tissue in 7 weeks hitoculture by the glucose-consumption tests. We determined that the new platinum drug has lower nephrotoxicity than cisplatin. Based on these results, this novel platinum (II) complex compound (PC) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• BMB Reports
• /
• 제31권6호
• /
• pp.560-564
• /
• 1998

Echinomycin-7 is an echinomycin derivative, Smethylated sulfonium perchlorate of echinomycin. We studied the in vitro cytotoxicity and in vivo antitumor activity of echinomycin-7 against P388 leukemia cells and compared the results with echinomycin. With respect to the cytotoxic effects, echinomycin-7 had cell line-dependent $IC_{50}$ values while echinomycin had similar values to several tumor cell lines. Also, in vivo antitumor activities were observed in tumor-bearing mice treated with both agents, which showed that echinomycin-7 had a broad therapeutic dose range. We also observed the apoptosis on leukemia cells treated with echinomycin-7 which exihibited the ladder pattern of DNA on electrophoresis. In addition to apoptosis, echinomycin-7 arrested $G_1/S$ phases of the cell cycle at the same time. We then examined the signaling pathway of echinomycin-7-induced apoptosis and showed that ERK of the MAP kinase family was activated and translocated into the nucleus by echinomycin-7 stimulation. This study suggests that echinomycin-7 acts as an antitumor agent through in vitro cytotoxicity and has in vivo antitumor activity against leukemia cells, and that the echinomycin-7- induced apoptosis might involve signal transduction via MAP kinases.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.357.1-357.1
• /
• 2002

Three-dimensional quantitative activity relationship (3D-QSAR) study for a series of arylsulfonylimidazolidinone derivatives with antitumor activity was conducted using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices anaysis (CoMSIA). The in vitro cytotoxicity against human lung carcinoma (A549) exhibited a strong correlation with steric and electrostatic factors of the molecules. (omitted)