Nonplanar Helicene Benzo[4]Helicenium for the Precise Treatment of Renal cell Carcinoma

Xiaozhen He; Fuwei Gan; Yan Zhou; Yuanliang Zhang; Peipei Zhao; Bingru Zhao; Qianyun Tang; Li Ye; Jun Bu; Junyang Mei; Ling Du; Huili Dai; Huibin Qiu; Peifeng Liu

doi:10.1002/smtd.202100770

Nonplanar Helicene Benzo[4]Helicenium for the Precise Treatment of Renal cell Carcinoma

Small Methods. 2021 Nov;5(11):e2100770. doi: 10.1002/smtd.202100770. Epub 2021 Sep 15.

Authors

Xiaozhen He^{1

2}, Fuwei Gan³, Yan Zhou^{1

2}, Yuanliang Zhang⁴, Peipei Zhao^{1

2}, Bingru Zhao^{1

2}, Qianyun Tang^{1

2}, Li Ye^{1

2}, Jun Bu^{1

2}, Junyang Mei^{1

2}, Ling Du^{1

2}, Huili Dai^{1

2}, Huibin Qiu³, Peifeng Liu^{1

2}

Affiliations

¹ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
² Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
³ School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, China.
⁴ State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.

PMID: 34927965
DOI: 10.1002/smtd.202100770

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.

Keywords: aromatic rings; helicene; kidney cancer; selectivity; water-soluble helicenes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Renal Cell / drug therapy*
Carcinoma, Renal Cell / genetics
Cell Cycle Checkpoints
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
DNA Damage
Gene Expression Profiling / methods*
Humans
Kidney Neoplasms / drug therapy*
Kidney Neoplasms / genetics
Male
Mice
Mice, Nude
Molecular Structure
Polycyclic Aromatic Hydrocarbons / chemical synthesis*
Polycyclic Aromatic Hydrocarbons / chemistry
Polycyclic Aromatic Hydrocarbons / pharmacology
Polycyclic Compounds / chemical synthesis*
Polycyclic Compounds / chemistry
Polycyclic Compounds / pharmacology
RNA-Seq
Xenograft Model Antitumor Assays

Substances

Polycyclic Aromatic Hydrocarbons
Polycyclic Compounds
helicenes

Abstract

Publication types

MeSH terms

Substances

Grants and funding