pheophorbide-a and Melanoma

In order to apply photodynamic therapy (PDT) to pigmented melanoma, the efficacy of PDT mediated by pheophorbide alpha from silkworm excreta (SPbalpha) and commercial Photofrin against B16F10 melanoma was comparatively studied from the in vivo assay using C57BL/6J mice. From in vitro PDT assay, the proliferation of B16F10 cells treated with SPbalpha (more than 0.5 microg/ml) and light illumination (1.2 J/cm2) were significantly inhibited with the necrotic response. This indicated that the photocytotoxicity of SPbalpha (665 nm) was not influenced by melanin from melanoma. From the assessment of the in vivo photosensitizing activity, the tumor growth was further delayed in groups treated with SPbalpha/PDT compared to that treated with Photofrin /PDT. The survival rate of tumor bearing mice treated with SPbalpha/PDT was closely associated with its photosensitizing effect. In addition, the photosensitizing effect of SPbalpha/PDT showed a dose dependent tendency in light illumination. These results demonstrated that B16F10 melanoma cells were significantly photosensitized by SPbalpha/PDT, regardless of the influence of melanin from melanoma, and SPbalpha/PDT at very low drug dose (1 mg/kg) and light dose (1.2 J/cm2) showed the photosensitizing efficacy surpassing Photofrin against B16F10 melanoma in mice system.

Topics: Animals; Bombyx; Cell Death; Cell Line, Tumor; Chlorophyll; Female; Light; Melanoma; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Photochemotherapy; Pigmentation; Survival Rate

Three pheophorbide-related compounds (1-3) were isolated from the leaves and stems of Clerodendrum calamitosum. The methyl ester of 3 (6) and the known (10S)-hydroxypheophytin a (7) also were isolated from leaves of the related plant Clerodendrum cyrtophyllum. Compounds 1 and 6 were isolated for the first time as naturally occurring products from a plant source. All structures were elucidated by detailed spectroscopic analysis. Biological evaluation showed that 1 and 2 exhibited strong cytotoxicity against human lung carcinoma (A549), ileocecal carcinoma (HCT-8), kidney carcinoma (CAKI-1), breast adenocarcinoma (MCF-7), malignant melanoma (SK-MEL-2), ovarian carcinoma (1A9), and epidermoid carcinoma of the nasopharynx (KB), and its etoposide- (KB-7d), vincristine- (KB-VCR), and camptothecin-resistant (KB-CPT) subclones. Compound 3 was less cytotoxic than 1 and 2. Compounds 4-6, the methyl esters of 1-3, showed strongly increased cytotoxicity compared with the parent acids. Interestingly, 6 was the most active derivative among these compounds. Compound 7 was inactive.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Camptothecin; Cell Survival; Chlorophyll; Dose-Response Relationship, Drug; Drug Resistance; Etoposide; Female; Humans; Ileal Neoplasms; KB Cells; Kidney Neoplasms; Lung Neoplasms; Magnetic Resonance Spectroscopy; Melanoma; Molecular Structure; Ovarian Neoplasms; Plant Leaves; Plant Stems; Plants, Medicinal; Stereoisomerism; Structure-Activity Relationship; Taiwan; Tumor Cells, Cultured; Vincristine