Farnesiferol c induces apoptosis via regulation of L11 and c-Myc with combinational potential with anticancer drugs in non-small-cell lung cancers

• Published in: Scientific reports 2016-05, Vol.6 (1), p.26844-26844, Article 26844
• Main Authors: Jung, Ji Hoon, Kim, Moon Joon, Lee, Hyemin, Lee, Jihyun, Kim, Jaekwang, Lee, Hyun Joo, Shin, Eun Ah, Kim, Yoon Hyeon, Kim, Bonglee, Shim, Bum Sang, Kim, Sung-Hoon
• Format: Article
• Language: English
• Subjects: 13; 13/31; 13/89; 631/67/1612/1350; 631/67/2195; 96; 96/1; 96/109; Antineoplastic Agents - administration & dosage; Apoptosis - drug effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Cell Line, Tumor; Cell Survival - drug effects; Coumarins - administration & dosage; Cyclin D1 - metabolism; Cyclin-Dependent Kinase 4 - metabolism; Doxorubicin - administration & dosage; Drug Therapy, Combination; G1 Phase Cell Cycle Checkpoints - drug effects; Humanities and Social Sciences; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; multidisciplinary; Proto-Oncogene Proteins c-myc - metabolism; Puromycin - administration & dosage; Ribosomal Proteins - metabolism; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep26844

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.