Hypericin and Photodynamic Therapy Decreases Human Pancreatic Cancer in Vitro and in Vivo

Liu, Carson D.; Kwan, David; Saxton, Romaine E.; McFadden, David W.

doi:10.1006/jsre.2000.5949

Cited by 88 publications

(45 citation statements)

References 32 publications

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“…Hypericin has been regarded as a promising photosensitizing agent for its characteristic of light-dependent antineoplastic and antiviral activity [16]. Hypericin-mediated PDT has obtained increasing interests as a potential treatment for various cancers [17][18][19]. Currently, multiple pathways have been found to involved in the tumor cell death program induced by hypericin-mediated PDT, such as mitochondrial pathway [20,21], lysosomal damage [22], alternation of intracellular pH level [23,24], Bcl-2 phosphorylation by CDK-1 [25] as well as the increase of intracellular Ca2+ stimulated apoptosis [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro

Zhang

Shao

et al. 2014

Cancer Cell Int

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Section: Introductionmentioning

confidence: 99%

Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro

Zhang

Shao

et al. 2014

Cancer Cell Int

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“…In vitro and in vivo photodynamic effects inducing apoptosis and/or necrosis of various malignant cells, such as human glioblastoma cell lines (22), human HL-60 promyelocytic leukaemia cells and CD4 + T-cells (23), rat bladder transitional cell carcinoma (24), human colon carcinoma and hepatoma cell lines (25) as well as human pancreatic cancer (26), were demonstrated. In vitro hypericin accumulates in glioma cells significantly higher than in neurones (27,28).…”

Section: Introductionmentioning

confidence: 99%

Selective enrichment of hypericin in malignant glioma: Pioneering in vivo results

Noell

Mayer²,

Strauß³

et al. 2011

Int J Oncol

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Abstract. Malignant gliomas are diffuse infiltrative growing tumors with a poor prognosis despite treatment with a combination of surgery, radiotherapy and chemotherapy. It has been shown recently that complete tumor resection improves the survival time significantly. Hypericin, a component of St. Johns Wort, is one of the most powerful photosensitizers in nature. The aim of the present study was to investigate accumulation of hypericin in intracerebral implanted malignant glioma in vivo. Rats underwent stereotactic implantation of C6 glioma cells. After intravenous administration of hypericin (5 mg per kg body weight), accumulation of the compound was studied in tumor, the infiltration zone surrounding the tumor and healthy brain (contralateral hemisphere) by fluorescence microscopy between 0 and 48 h after injection. Results were compared by one-way analysis of variance. For post hoc pair-wise comparison the Tukey-Kramer HSD test was used. Accumulation of hypericin was significantly higher in C6 glioma as compared to normal tissue. Maximum hypericin uptake was achieved at 24 h after injection. Ratios of fluorescence intensity between tumor and normal tissue as well as infiltration zone and normal tissue of about 6.1:1 and 1.4:1 were found. Considering tissue auto-fluorescence, fluorescence ratios of about 19.8:1 and 2.5:1 were calculated, respectively. Therefore, hypericin seems to be quite an effective fluorescence marker for the detection of glioma in vivo. To the best of our knowledge, the present study demonstrates for the first time that hypericin accumulates selectively in intracerebral implanted C6 glioma in vivo after systemic (intravenous) administration.

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“…[1][2][3] Hypericin, isolated from plants of the genus Hypericum, is one of the photosensitizers being investigated as a promising PDT agent due to its potent light-dependent antineoplastic and antiviral activities. 4 Using different tumor models, we [5][6][7] and others 8,9 have shown that PDT with hypericin significantly inhibits tumor growth. For instance, in the RIF-1 tumor model, we found that PDT performed at 0.5 hr after i.v.…”

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confidence: 99%

Photodynamic therapy with hypericin induces vascular damage and apoptosis in the RIF‐1 mouse tumor model

Chen

Roskams

et al. 2001

Intl Journal of Cancer

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Hypericin, a polycyclic quinone obtained from plants of the genus Hypericum, has been proven to be a potent photosensitizer. The mechanism of tumor eradication and mode of cell death induced by in vivo photodynamic therapy (PDT) with hypericin were investigated in the present study using 2 therapeutic protocols. RIF-1 tumors were exposed to laser light at either 0.5 hr or 6 hr after hypericin administration (5 mg/kg, i.v.). A significant reduction in tumor perfusion, as determined by the retention of fluorescein in the tumor tissue, was detected immediately after both PDT treatments. Further decrease in tumor perfusion was observed in the hours after treatment. The re-establishment of tumor perfusion, however, occurred 24 hr after 6 hr-interval PDT, but not after 0.5 hr-interval PDT. The kinetics of tumor cell survival estimated by the in vivo/in vitro clonogenic assay revealed no or limited cell death when tumors were explanted immediately after irradiation, whereas a delayed but progressive cell death was detected when tumors remained in situ after both PDT treatments. The detection of nucleosomal DNA fragmentation by agarose gel electrophoresis or TUNEL assay and the assessment of cell morphology by light microscopy indicated that apoptosis was the most prominent tumor response to hypericin-mediated PDT. Furthermore, immunohistochemical analysis of the tumor tissue showed an increased expression of both Fas and Fas ligand after irradiation, suggesting that this cell death pathway might contribute to the overall PDT-induced apoptotic response. In conclusion, our results demonstrate that apoptosis, likely occurring as a result of vascular damage, is responsible for the tumor eradication by PDT with hypericin in this tumor model.

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Hypericin and Photodynamic Therapy Decreases Human Pancreatic Cancer in Vitro and in Vivo

Cited by 88 publications

References 32 publications

Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro

Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro

Selective enrichment of hypericin in malignant glioma: Pioneering in vivo results

Photodynamic therapy with hypericin induces vascular damage and apoptosis in the RIF‐1 mouse tumor model

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