Hypericin-induced apoptosis of human malignant glioma cells is light-dependent, independent of bcl-2 expression, and does not require wild-type p53
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Hypericin-induced apoptosis of human malignant glioma cells is light-dependent, independent of bcl-2 expression, and does not require wild-type p53. / Weller, M; Trepel, M; Grimmel, C; Schabet, M; Bremen, D; Krajewski, Stan; Reed, John C.
In: NEUROL RES, Vol. 19, No. 5, 10.1997, p. 459-70.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Hypericin-induced apoptosis of human malignant glioma cells is light-dependent, independent of bcl-2 expression, and does not require wild-type p53
AU - Weller, M
AU - Trepel, M
AU - Grimmel, C
AU - Schabet, M
AU - Bremen, D
AU - Krajewski, Stan
AU - Reed, John C
PY - 1997/10
Y1 - 1997/10
N2 - Hypericin and tamoxifen are experimental agents for the adjuvant chemotherapy of malignant glioma. We report that hypericin and tamoxifen induce apoptosis of 7 human malignant glioma cell lines in a concentration- and time-dependent manner. Illumination is essential for the cytotoxicity of hypericin but not tamoxifen. Apoptosis is unaffected by inhibitors of RNA and protein synthesis or free radical scavengers, does not require wild-type p53 activity, and occurs in glioma cells expressing high levels of bcl-2. There is no correlation between hypericin and tamoxifen-induced cytotoxicity and inhibition of protein kinase C (PKC). Ectopic expression of a murine bcl-2 transgene provides modest protection from tamoxifen but does not affect hypericin toxicity. Hypericin and tamoxifen do not modulate glioma cell killing induced by tumor necrosis factor-alpha (TNF-alpha) or CD95 ligand. Both drugs augment the acute cytotoxicity of various cancer chemotherapy drugs but fail to shift their EC50 values in modified colony formation assays. These data do not provide further supportive evidence how to enhance the limited efficacy of tamoxifen treatment for human malignant glioma. However, hypericin is a promising agent for the treatment of malignant glioma if local photodynamic activation of hypericin in the glioma tissue can be achieved.
AB - Hypericin and tamoxifen are experimental agents for the adjuvant chemotherapy of malignant glioma. We report that hypericin and tamoxifen induce apoptosis of 7 human malignant glioma cell lines in a concentration- and time-dependent manner. Illumination is essential for the cytotoxicity of hypericin but not tamoxifen. Apoptosis is unaffected by inhibitors of RNA and protein synthesis or free radical scavengers, does not require wild-type p53 activity, and occurs in glioma cells expressing high levels of bcl-2. There is no correlation between hypericin and tamoxifen-induced cytotoxicity and inhibition of protein kinase C (PKC). Ectopic expression of a murine bcl-2 transgene provides modest protection from tamoxifen but does not affect hypericin toxicity. Hypericin and tamoxifen do not modulate glioma cell killing induced by tumor necrosis factor-alpha (TNF-alpha) or CD95 ligand. Both drugs augment the acute cytotoxicity of various cancer chemotherapy drugs but fail to shift their EC50 values in modified colony formation assays. These data do not provide further supportive evidence how to enhance the limited efficacy of tamoxifen treatment for human malignant glioma. However, hypericin is a promising agent for the treatment of malignant glioma if local photodynamic activation of hypericin in the glioma tissue can be achieved.
KW - Antibiotics, Antineoplastic
KW - Antigens, CD95
KW - Antineoplastic Agents
KW - Antineoplastic Agents, Hormonal
KW - Apoptosis
KW - Cell Division
KW - Drug Resistance
KW - Glioma
KW - Humans
KW - Light
KW - Naphthalenes
KW - Perylene
KW - Protein Kinase C
KW - Protein Synthesis Inhibitors
KW - Proto-Oncogene Proteins
KW - Proto-Oncogene Proteins c-bcl-2
KW - RNA
KW - Tamoxifen
KW - Tumor Cells, Cultured
KW - Tumor Suppressor Protein p53
KW - bcl-2-Associated X Protein
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
M3 - SCORING: Journal article
C2 - 9329022
VL - 19
SP - 459
EP - 470
IS - 5
ER -