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.

125I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, survivin, livin and caspase-9 expression in lung carcinoma xenografts

“…Primary lung cancer is the most common malignancies [ 1 ] and the leading cause of tumor-associated mortality [ 2 – 8 ] in gender-independent populations. Approximately 1.8 million new cases are diagnosed and near 1.6 million fatal cases are estimated annually worldwide, accounting for 19.4% of total cancer mortality, and the 5-year overall survival rate is less than 20% [ 2 , 5 , 7 , 9 – 12 ] Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers and small cell lung cancer (SCLC) was about 15% [ 3 , 4 , 6 , 13 – 15 ], and more than 50% NSCLC are adenocarcinoma [ 2 , 7 ].Surgery remains the main curative selection for patients with early-stage non-small cell lung cancer. However, less than 20% of patients with non-small cell lung cancer who have not yet been diagnosed with advanced disease can be cured by surgical resection [ 16 ].…”

“…85% of lung cancers and small cell lung cancer (SCLC) was about 15% [3,4,6,[13][14][15], and more than 50% NSCLC are adenocarcinoma [2,7].Surgery remains the main curative selection for patients with early-stage nonsmall cell lung cancer. However, less than 20% of patients with non-small cell lung cancer who have not yet been diagnosed with advanced disease can be cured by surgical resection [16].…”

The nucleolus, an ally, and an enemy of cancer cells

“…In addition, a phytochemical, farnesiferol C (FC), reduces the levels of both c-Myc and RPL11, which co-regulate each other, as well as it attenuates the expression of survival genes leading to apoptosis in NSCLC. Furthermore, puromycin or Dox combined with FC enhance its cytotoxic effect (Jung et al 2016 ).…”

125 I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, Survivin，Livin and Caspase-9 expression in lung carcinoma xenografts

“…Primary lung cancer is the most common malignancies (1) and the leading cause of tumorassociated mortality (2)(3)(4)(5)(6)(7)(8) in gender-independent populations. Approximately 1.8 million new examples are diagnosed and near 1.6 million fatal cases were estimated annually worldwide, accounting for 19.4% of total cancer mortality, and the total 5-year survival rate was less than 20% (2,5,7,(9)(10)(11)(12) Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and small cell lung cancer (SCLC) was about 15% (3,4,6,(13)(14)(15), which more than 50% NSCLC is adenocarcinoma (2,7).Surgery remains the main curative selection for patients with early-stage non-small cell lung cancer. However, in NSCLC patients with advanced disease has not been diagnosed, fewer than 20% of patients can be cured by surgical resection (16).…”