Thromboplastic and fibrinolytic activities of cultured human cancer cell lines

Kinjo, Mitsuru; Oka, Kazunari; Naito, Seiji; Kohga, Shin; Tanaka, Kenzö; Oboshi, Shoichi; Hayata, Y; Yasumoto, K

doi:10.1038/bjc.1979.3

Cited by 77 publications

(32 citation statements)

References 20 publications

(21 reference statements)

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“…Human tumour cell line PC-10 squamous lung carcinoma cell line was used in these experiments (Kinjo et al, 1979). Cells were maintained as a monolayer in RPMI-1640 medium (GIBCO, Grand Island, NY), supplemented with 10% (v/v) heat-inactivated foetal bovine serum (FBS) (Gibco) at 37"C in a 5% CO2/95% humidified air atmosphere.…”

Section: Methodsmentioning

confidence: 99%

Interactions of doxorubicin and cis-platin in squamous carcinoma cells in culture

Kohno

Ohnuma²,

Kaneko³

et al. 1988

Br J Cancer

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Summary Doxorubicin (DXR) has a positive inoculum effect and penetrates poorly into the core of multicellular tumour spheroids (MTS). Cis-platin (DDP) displays neither of these characteristics. We evaluated whether combining these 2 agents would influence the cell kill effect at a tumour mass level. MTS were produced from a PC-10 squamous lung carcinoma cell line. MTS were exposed to either drug first for h with different intervals between exposure. Cells were then trypsinized to a single cell suspension and subjected to clonogenic assay. Combination effects were analyzed by median effect plot analysis. The more MTS ml-' medium, the lower the cell kill effect of DXR. Simultaneous exposure to the 2 drugs was synergistic. DXR exposure first followed by DDP was less efficacious than, or the same as, the simultaneous exposure. In contrast, DDP followed by DXR was more efficacious with the best cell kill at a 1 h interval between each drug. This phenomenon was observed even at non-toxic doses of DDP. The fluorescent microscopic study of DXR indicated that prior exposure of MTS to DDP resulted in increased DXR penetration into the MTS core leading to heightened synergism with this sequence. These data suggest that the proper combination of DXR plus DDP should be in sequence with DDP first. Clinical, toxicological and pharmacological trials of DDP administration first, followed by DXR, are warranted.Doxorubicin (DXR) and cis-platin (DDP) are both highly active anticancer agents widely used in the treatment of human cancer. We introduced a combination of these 2 agents, termed A & P (adriamycin and platinum) (Vogl et al., 1976), which has become the basis, by adding more drugs, for the treatment of patients with ovarian cancer, small cell lung cancer and other neoplasms. Recently, we have demonstrated that DXR has a positive inoculum effect in vitro and loses efficacy at high cell densities, whereas DDP does not (Ohnuma et al., 1986). Moreover, we have shown that DXR penetrates poorly into the core of multicellular tumour spheroids (MTS) whereas DDP shows no such penetration gradient (Inoue et al., 1985). These pharmacological differences at the tumour mass level indicate that DXR should be best used when tumour size is small and cell density low. Therefore, we hypothesized that the proper sequence of A & P should be DDP first, followed by DXR, rather than vice versa. This communication sets forth the experimental proof of our hypothesis and elucidates a possible mechanism for this effect. Materials and methodsHuman tumour cell line PC-10 squamous lung carcinoma cell line was used in these experiments (Kinjo et al., 1979). Cells were maintained as a monolayer in RPMI-1640 medium (GIBCO, Grand Island, NY), supplemented with 10% (v/v) heat-inactivated foetal bovine serum (FBS) (Gibco) at 37"C in a 5% CO2/95% humidified air atmosphere. These cells were subcultured after trypsinization with 0.2% trypsin (Type III from Conditions of drug exposure and determination of cell survival After 3 weeks of culture, MTS with a diame...

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Section: Methodsmentioning

confidence: 99%

Interactions of doxorubicin and cis-platin in squamous carcinoma cells in culture

Kohno

Ohnuma²,

Kaneko³

et al. 1988

Br J Cancer

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“…In many cases, the treatment of animals with anticoagulant compounds results in an anti metastatic effect [32,33]. Fibrin deposition occurs around tumors [27], and is thought to provide tumors with a support structure [28] and/or aid the cells in avoiding immune sur veillance [28], Isolated tumor cells [34,35] and tumor cell fractions [36,37] possess PCA. This activity may be related to the metastatic potential of the tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Role of the Coagulation System in Tumor-Cell-Induced Platelet Aggregation and Metastasis

Cavanaugh

Sloane²,

Honn³

1988

Pathophysiol Haemos Thromb

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The ability of tumor cells to initiate coagulation and subsequent platelet aggregation is believed to facilitate the metastatic process. The mechanism by which tumor cells initiate thrombotic alterations is unclear. We have purified a plasma membrane protein platelet aggregating activity/procoagulant activity (PAA/PCA) from several rodent tumors which initiates the coagulation of homologous plasma and aggregation of homologous platelets by a mechanism independent of factor VII. This protein does not possess any proteinase activity; however, its activity is dependent upon the presence of factor X. In addition, PAA/PCA requires reconstitution with phospholipid for expression of activity. These results suggest that tumor cells express a unique protein which possesses procoagulant activity resulting in thrombin generation. Thrombin is responsible for subsequent tumor-cell-induced platelet aggregation.

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“…The present paper describes the further separation and structure elucidation of seven triterpenes, ␣-amyrin (1), uvaol (2), ursolic acid (3), ␤-amyrin (4), erythrodiol (5), lupeol (6) and betulin (7), two sterols, ␤-sitosterol (8) and ␤-sitosterol 3-O-␤-glucopyranoside (9), and one flavonoid, syringetin 3-O-␣-rhamnopyranoside (10) from the MeOH extract. The cytotoxic activity of 1, 3, 4, 6, 8 and 9 against human lung cancer cells (PC-12) (Kinjo et al, 1979) and human colon cancer cells (HCT116) (Brattain et al, 1981) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Mosmann, 1983) is also described.…”

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confidence: 99%

Cytotoxic Triterpenes and Sterol from the Fruit of Rabbiteye Blueberry (Vaccinium ashei)

Ono

Koto

Komatsu

et al. 2004

FSTR

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Seven triterpenes, ␣-amyrin (1), uvaol (2), ursolic acid (3), ␤-amyrin (4), erythrodiol (5), lupeol (6) and betulin (7), two sterols, ␤-sitosterol (8) and ␤-sitosterol 3-O-␤-glucopyranoside (9), and one flavonoid, syringetin 3-O-␣-rhamnopyranoside (10) were isolated from the methanol extract of the fruit of rabbiteye blueberry (Vaccinium ashei). Their chemical structures were determined on the basis of spectroscopic data. Among them, 3, 4 and 9 exhibited moderate growth inhibitory activity against human lung cancer cells (PC-12) and human colon cancer cells (HCT116) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.

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Thromboplastic and fibrinolytic activities of cultured human cancer cell lines

Cited by 77 publications

References 20 publications

Interactions of doxorubicin and cis-platin in squamous carcinoma cells in culture

Interactions of doxorubicin and cis-platin in squamous carcinoma cells in culture

Role of the Coagulation System in Tumor-Cell-Induced Platelet Aggregation and Metastasis

Cytotoxic Triterpenes and Sterol from the Fruit of Rabbiteye Blueberry (Vaccinium ashei)

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