Nonplanar Helicene Benzo[4]Helicenium for the Precise Treatment of Renal cell Carcinoma
Xiaozhen He1,2, Fuwei Gan3, Yan Zhou1,2
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Abstract:
Immune and targeted therapy are becoming the first-line treatment for renal cell carcinoma (RCC). However, therapeutic outcomes are limited due to the low efficiency and side effect. Here, it is found that helicenes are able to exhibit an anticancer capability through changing the molecular structure from planar to nonplanar. Furthermore, the cytotoxicity in vitro and cancer inhibition ability of nonplanar helicenes increase with its aromatic rings' number. It is further demonstrated that benzo[4]helicenium shows the specific killing efficiency against the RCC cancer as compared to normal kidney cells. This is majorly originated from a more selective damage of benzo[4]helicenium for mitochondria and DNA in RCC cancer cells, not the normal kidney. The selective killing ability of benzo[4]helicenium makes it have potential to be used as a targeted drug for the precise treatment of RCC.
Insights
Nonplanar helicenes show anticancer effects against renal cell carcinoma (RCC). Benzo[4]helicenium selectively damages RCC cells, offering potential as a targeted therapy for kidney cancer.
Area of Science:
- Organic Chemistry
- Oncology
- Molecular Biology
Background:
- Renal cell carcinoma (RCC) treatments have limited efficacy and side effects.
- Immune and targeted therapies are current first-line treatments for RCC.
- Novel therapeutic strategies are needed to improve RCC treatment outcomes.
Purpose of the Study:
- To investigate the anticancer capabilities of helicenes against RCC.
- To explore the structure-activity relationship of helicenes in cancer inhibition.
- To evaluate the potential of benzo[4]helicenium as a targeted therapy for RCC.
Main Methods:
- Synthesis and structural modification of helicenes.
- In vitro cytotoxicity assays against RCC and normal kidney cells.
- Mitochondrial and DNA damage assessment in cancer cells.
- In vivo cancer inhibition studies.
Main Results:
- Nonplanar helicenes exhibit anticancer activity, with potency increasing with aromatic ring number.
- Benzo[4]helicenium demonstrates selective cytotoxicity against RCC cells compared to normal kidney cells.
- Benzo[4]helicenium selectively damages mitochondria and DNA in RCC cells.
Conclusions:
- Helicenes, particularly nonplanar structures like benzo[4]helicenium, possess significant anticancer properties.
- Benzo[4]helicenium's selective targeting of RCC cells offers a promising avenue for precise kidney cancer treatment.
- This study highlights the potential of benzo[4]helicenium as a novel targeted drug for renal cell carcinoma.
