title: Farnesiferol c induces apoptosis via regulation of L11 and c-Myc with combinational potential with anticancer drugs in non-small-cell lung cancers.
abstract: Though Farnesiferol c (FC) has been reported to have anti-angiogenic and antitumor activity, the underlying antitumor mechanism of FC still remains unclear. Thus, in the present study, we investigated the apoptotic mechanism of FC in human H1299 and H596 non-small lung cancer cells (NSCLCs). FC significantly showed cytotoxicity, increased sub-G1 accumulation, and attenuated the expression of Bcl-2, Bcl-xL, Survivin and procaspase 3 in H1299 and H596 cells. Furthermore, FC effectively suppressed the mRNA expression of G1 arrest related genes such as Cyclin D1, E2F1 transcription factor and CDC25A by RT-PCR. Interestingly, FC inhibited the expression of c-Myc, ribosomal protein L11 (L11) and nucleolin (NCL) in H1299 and H596 cells. Of note, silencing of L11 by siRNA transfection enhanced the expression of c-Myc through a negative feedback mechanism, while c-Myc knockdown downregulated L11 in H1299 cells. Additionally, combined treatment of FC and puromycin/doxorubicin promoted the activation of caspase 9/3, and attenuated the expression of c-Myc, Cyclin D1 and CDK4 in H1299 cells compared to single treatment. Taken together, our findings suggest that FC induces apoptosis and G1 arrest via regulation of ribosomal protein L11 and c-Myc and also enhances antitumor effect of puromycin or doxorubicin in NSCLCs.
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jung
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Moon Joon
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Jaekwang
authors.initials: J
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Eun Ah
authors.initials: EA
authors.lastname: Shin
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Yoon Hyeon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Bonglee
authors.initials: B
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Bum Sang
authors.initials: BS
authors.lastname: Shim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000008:administration & dosage*; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D011691:Puromycin / Q000008:administration & dosage; D012269:Ribosomal Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D003374:Coumarins; D016271:Proto-Oncogene Proteins c-myc; D012269:Ribosomal Proteins; C027624:ribosomal protein L11; D019938:Cyclin D1; D011691:Puromycin; C553326:farnesiferol C; D004317:Doxorubicin; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4