Abstract LB-282: HO-4073, a potent curcumin analog, reverses chemo- and radio-resistance in head and neck cancer
Authors: Kumar Bhavna , Hou Yanjun , Kumar Pawan , Selvendiran Karuppaiyah , Hideg Kalman , Kuppusamy Perrianan , Teknos Theodoros N. 
Published: February 2011

Objectives of the study: Chemotherapy and radiotherapy constitute the standard modality of treatment for localized head and neck squamous cell carcinomas (HNSCC). However, many patients fail to respond and relapse after such treatments due to the acquisition of chemo- and radio-resistance. Therefore, there is an urgent need to develop novel drugs that could reverse the resistant phenotype. Curcumin, the constituent of the spice turmeric has been shown to have anti-inflammatory, anti-oxidant and anti-proliferative properties in several tumor types. However, use of curcumin has been limited due to its poor absorption. Recently, a novel class of curcumin analogs, diarylidenylpiperidones (DAPs), has been developed by incorporating a piperidone link to the beta-diketone structure and fluoro substitutions on the phenyl groups. We have observed that these DAP compounds, in general are more effective than curcumin in inhibiting the proliferation of a variety of cancer cell lines and xenograft tumors. The objective of this study was to evaluate the effectiveness of HO-4073, a DAP compound, in reversing chemo-and radio-resistance in head and neck cancer cell lines. HO-4073 is a parafluorinated variant of DAPs.

Methodology: The study was performed using two established human head and neck cancer cell lines, Cell-viablity assay was performed by MTT. Apoptosis was quantified by Annexin V staining. Cleaved caspase-3 and JAK/STAT3 signaling proteins were measured by Western blot.

Results: Our results showed that HO-4073 is a potent anti-tumor agent and it significantly inhibited cell proliferation in all the head and neck cancer cell lines tested in a dose- and time-dependent manner, irrespective of p53 mutation status or human papillomavirus positivity. In addition, pretreatment of a highly chemo- and radio-resistant HNSCC cell line (UM-SCC-74A) with HO-4073 (2.5 M) significantly reversed the chemo resistance as observed by cell viability assay (MTT), apoptosis assay (Annexin V binding) and cleaved caspase-3 (Western blot). HO-4073 induced chemo- and radio-sensitivity via the inhibition of JAK/STAT3 pathway. To further examine the effect of HO-4073 on chemo-resistance, we established a cisplatin-resistant cell line (CAL 27-PT) in the laboratory by growing a tongue cancer cell line CAL 27 in increasing concentrations of cisplatin. CAL 27-PT is highly resistant to cisplatin (IC50 20 M) as compared to the parental cell line (IC50 2 M). Treatment with HO-4073 resulted in a 4-fold increase in apoptosis in the cisplatin resistant CAL 27-PT as compared to untreated cells.

Conclusion: Taken together, our results suggest that HO-4073 is a potent anti-tumor agent and it can be used to overcome chemo- and radio-resistance in head and neck cancer cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-282.