Abstract
The combination of fenretinide and selenite on ovarian cancer cells was investigated to assess its effects on proliferation and ability to induce apoptosis. Our results showed that fenretinide and selenite in combination significantly suppress the proliferation of ovarian cancer cells and induced apoptosis (including reactive oxygen species generation, and the loss of mitochondrial membrane potential) compared with either drug used alone. The caspase3/9-dependent pathway was triggered significantly in combination treatment, and moreover, the AMPK pathway also mediated the apoptosis induction in fenretinide and selenite combination. Fenretinide and selenite combination treatment was demonstrated to suppress tumor growth in vivo, this drug combination has been thus found to have an enhanced anti-tumor effect on ovarian cancers cells.
Highlights
Gynecologic cancers such as ovarian cancer is a common type of cancer in women, the prognosis for patients with these advanced cancers is extremely difficult; and the conventional chemotherapy does not have clinical efficiency for advanced ovarian cancer patients [1]
Two different additional ovarian cancer cell lines, OVCAR3 and A2780, were used to test the potentiating or enhanced effect of this combination; the cell viability of two cell lines significantly decreased (Figure 1H), indicating that the fenretinide and selenite combination could suppress the growth of ovarian cancer cell lines additively
SKOV3 cells was measured by MTT after exposure of fenretinide with different concentrations for 24 h (A); 48 h (B) and 72 h (C); Viability of SKOV3 cells measurement after exposure of selenite with different concentration for 24 h (D); 48 h (E) and 72 h (F); SKOV3 cells’ viability under different concentration of fenretinide and selenite combination treated for 24 h and 48 h (G); Viability assay using two additional different ovarian cell lines (OVCAR3 and A2780) after exposure of drugs alone (10 μmol/L fenretinide, 10 μmol/L selenite) or drug combination (10 μmol/L fenretinide plus 10 μmol/L selenite) for 48 h, 10 μg/mL cisplatin treatment used as positive control (H)
Summary
Gynecologic cancers such as ovarian cancer is a common type of cancer in women, the prognosis for patients with these advanced cancers is extremely difficult; and the conventional chemotherapy does not have clinical efficiency for advanced ovarian cancer patients [1]. The effects of selenium compounds depend on the drug administration and dose used. At low doses, it has antioxidant with cancer preventing properties; while at a higher dose it has been shown promising tumor specific cytotoxic effect. Clinical trials have shown that selenium is effective for the prevention of cutaneous melanoma [26], and the drug as part of a combined drug treatment may have an enhanced anti-tumor effect on some cancer cells [27]. In present study, we examined the potentiating or enhanced effect of fenretinide when combined with selenite in ovarian cancer cells
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