Comparative effects of RRR-alpha- and RRR-gamma-tocopherol on proliferation and apoptosis in human colon cancer cell lines

BACKGROUND: Mediterranean societies, with diets rich in vitamin E isoforms, have a lower risk for colon cancer than those of northern Europe and the Americas. Vitamin E rich diets may neutralize free radicals generated by fecal bacteria in the gut and prevent DNA damage, but signal transduction activities can occur independent of the antioxidant function. The term vitamin E represents eight structurally related compounds, each differing in their potency and mechanisms of chemoprevention. The RRR-γ-tocopherol isoform is found primarily in the US diet, while RRR-α-tocopherol is highest in the plasma. METHODS: The effectiveness of RRR-α- and RRR-γ-tocopherol at inhibiting cell growth and inducing apoptosis in colon cancer cell lines with varying molecular characteristics (SW480, HCT-15, HCT-116 and HT-29) and primary colon cells (CCD-112CoN, nontransformed normal phenotype) was studied. Colon cells were treated with and without RRR-α- or RRR-γ-tocopherol using varying tocopherol concentrations and time intervals. Cell proliferation and apoptosis were measured using the trypan blue assay, annexin V staining, DNA laddering and caspase activation. RESULTS: Treatment with RRR-γ-tocopherol resulted in significant cell death for all cancer cell lines tested, while RRR-α-tocopherol did not. Further, RRR-γ-tocopherol treatment showed no cytotoxicity to normal colon cells CCD-112CoN at the highest concentration and time point tested. RRR-γ-tocopherol treatment resulted in cleavage of PARP, caspase 3, 7, and 8, but not caspase 9. Differences in the percentage cell death and apoptosis were observed in different cell lines suggesting that molecular differences in these cell lines may influence the ability of RRR-γ-tocopherol to induce cell death. CONCLUSION: This is the first study to demonstrate that multiple colon cancer cell lines containing varying genetic alterations will under go growth reduction and apoptosis in the presence of RRR-γ-tocopherol without damage to normal colon cells. The amount growth reduction was dependent upon the molecular signatures of the cell lines. Since RRR-γ-tocopherol is effective at inhibition of cell proliferation at both physiological and pharmacological concentrations dietary RRR-γ-tocopherol may be chemopreventive, while pharmacological concentrations of RRR-γ-tocopherol may aid chemotherapy without toxic effects to normal cells demonstrated by most chemotherapeutic agents

Best Practices for the Coordinated Care of Patients With Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy.

AbstractNeuroendocrine tumors (NETs) are rare, diverse malignancies; approximately two thirds originate in the gastrointestinal tract and pancreas and are known as gastroenteropancreatic NET. Most cases are diagnosed in the advanced or metastatic setting and overexpress somatostatin receptors. Recommended first-line treatment is somatostatin analogs; however, disease progression is common. [177Lu]Lu-DOTA-TATE is a radiolabeled peptide receptor radionuclide therapy (PRRT) indicated for the treatment of adult patients with somatostatin receptor-positive foregut, midgut, and hindgut gastroenteropancreatic NETs and progression on first-line somatostatin analogs. Many primary oncology practices may lack the staff, expertise, and infrastructure to treat patients with PRRT and primary oncologists may therefore refer their patients to a NET specialist at a tertiary center for treatment. Given the amount of organization required, PRRT treatment may seem to be complex; however, this process will be managed by a care coordinator who acts as a consistent point of contact for primary physicians regarding the care of their patients and ensures blood tests and scans are scheduled. In this article, we share our opinions, procedures, workflow, best practice, and roles and responsibilities when caring for patients receiving [177Lu]Lu-DOTA-TATE and focus on the role of the primary oncologist before, during, and after PRRT treatment