Abstract
Anticancer properties of tyrindoleninone and 6-bromoisatin from Dicathais orbita were tested against physiologically normal primary human granulosa cells (HGC) and reproductive cancer cell lines. Tyrindoleninone reduced cancer cell viability with IC50 values of 39 µM (KGN; a tumour-derived granulosa cell line), 39 μM (JAr), and 156 μM (OVCAR-3), compared to 3516 μM in HGC. Apoptosis in HGC’s occurred after 4 h at 391 µM tyrindoleninone compared to 20 µM in KGN cells. Differences in apoptosis between HGC and KGN cells were confirmed by TUNEL, with 66 and 31% apoptotic nuclei at 4 h in KGN and HGC, respectively. These marine compounds therefore have potential for development as treatments for female reproductive cancers.
Highlights
Gynaecological cancers of the ovary, cervix and endometrial are less common than either lung or breast cancer in women, but the mortality rates are higher due to late diagnosis [1,2]
As no marine natural products appear to have been previously tested for cytotoxicity against human primary granulosa cells, this study presents a new model for screening anticancer agents for female reproductive cancers
LC/MS of the purified fractions identified one major compound in fraction one (0.120 g) at tR 11.32 min which corresponded to the molecular mass of tyrindoleninone (ESI/MS insert m/z 255, 257 isotopes for bromine Br79, Br81; Figure 1A)
Summary
Gynaecological cancers of the ovary, cervix and endometrial are less common than either lung or breast cancer in women, but the mortality rates are higher due to late diagnosis [1,2]. In phase II trials, Dolastatin-10 had minimal activity against breast and platinum-sensitive ovarian cancer [24,25] Another bioactive compound Kahalalide F, isolated from the marine mollusc, Elysia rufescens [26], has shown anti-tumour activity in breast, hepatoma, melanoma and pancreatic carcinomas in phase I clinical trials [9,27]. The indole derivatives tyrindoleninone, tyrindolinone, 6-bromoisatin and 6,6′-dibromoindirubin, from the Muricidae family of marine gastropods, have anti-cancer properties [30,31,32] In vitro, these indole compounds inhibited cell growth in solid tumour cell lines from the colon and breast, and induced apoptosis and necrosis in T-cell lymphoma cells [30]. As no marine natural products appear to have been previously tested for cytotoxicity against human primary granulosa cells, this study presents a new model for screening anticancer agents for female reproductive cancers
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