title: N-3 PUFAs have antiproliferative and apoptotic effects on human colorectal cancer stem-like cells in vitro.
abstract: The n-3 polyunsaturated fatty acids have been shown to inhibit the induction and progression of many kinds of tumor and to increase the therapeutic effects of numerous chemotherapeutics, but their anticancer effect on cancer stem cells from colorectal cancer has not been described previously. In the present study, we cultivated spheres from the SW620 cell line in serum-free medium and evaluated the features of the spheres by immunofluorescence, cell cycle distribution, resistance to chemotherapeutics and soft agar clone formation, and the spheres were shown to be cancer stem-like cells through tumorigenicity in athymic nude mice. Reverse transcriptase polymerase chain reaction analysis of pluripotency genes, such as Sox-2, Oct-4 and Bmi-1, showed that the spheres were generated by dedifferentiation of SW620 cells. The study explored the use of n-3 polyunsaturated fatty acids (PUFAs) in spheres, which were treated with two n-3 PUFAs [docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA)]. Treatment of the spheres with DHA and EPA alone or in combination for 72 h led to apoptosis and the progressive loss of viability and DNA fragmentation and an increase in annexin V expression. DHA and EPA can enhance the chemotherapeutic sensitivity effect of 5-Fu and mitomycin C, especially DHA combined with EPA. Taken together, these results provide evidence that n-3 PUFAs exert a direct anticancer action that may contribute to their antiproliferative and proapoptotic effect on the cancer stem-like cells.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Shi
authors.initials: S
authors.lastname: Fang
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Zhang
authors.forename: Li-Xiao
authors.initials: LX
authors.lastname: Xu
authors.forename: Zhan-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Kai-Tao
authors.initials: KT
authors.lastname: Yuan
authors.forename: Cong-Long
authors.initials: CL
authors.lastname: Xue
authors.forename: Hong-Lan
authors.initials: HL
authors.lastname: Yu
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Li
authors.forename: Han-Ping
authors.initials: HP
authors.lastname: Shi
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005472:Fluorouracil / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism
chemical_list: D017304:Annexin A5; D000970:Antineoplastic Agents; D004281:Docosahexaenoic Acids; D016685:Mitomycin; D015118:Eicosapentaenoic Acid; D005472:Fluorouracil