Flavonoid-Alkylphospholipid Conjugates Elicit Dual Inhibition of Cancer Cell Growth and Lipid Accumulation

Cancer constitutes a major global health burden, and cancer development is impacted by not only genetic factors but also environmental concerns such as obesity, smoking, infections etc. Individuals who are obese or overweight often have high risk of developing carcinoma. This is because elevated lipid levels, caused by enhanced lipid synthesis and aberrant lipid accumulation, are able to induce carcinogenesis and accelerate cancer metastasis. Here, we report a series of novel dual-functional compounds with both anticancer activity and the ability to lower lipid accumulation.

These compounds are hybrid conjugates of the natural product quercetin and synthetic alkylphospholipids (APLs). Quercetin is a flavonoid antioxidant, and affects the heat shock pathway and lipid metabolism, whereas APLs have proven anticancer activity. Indeed, the identifed active compounds outperformed the parent compounds (quercetin and APLs) in terms of their anticancer activity, while also significantly suppressed lipid accumulation and down-regulated heat-shock proteins and antiapoptotic proteins. Consequently, these conjugates constitute a novel promising structural paradigm in the discovery of new anticancer candidates. This study may also open new avenues for developing therapeutic agents to treat other lipid accumulation-related diseases, such as cardiovascular diseases, obesity and diabetes etc.

Figure 1. (A) Chemical structures of the natural product quercetin, the synthetic alkylphospholipid drugs miltefosine and edelfosine, and their conjugates Id and IIc developed in this work; (B) their antiproliferative activity against cancer cells; and (C) their inhibition on lipid accumulation in cancer cells.



This is a collaborative work among Chongqing University in China, Centre de Recherche en Cancerologie de Marseille (CRCM) and Centre Interdisciplinaire de Nanoscience de Marseille (CINaM) in France under the frame of the French-Chinese cooperation program XUGUANGQI.


Flavonoid-Alkylphospholipid Conjugates Elicit Dual Inhibition of Cancer Cell Growth and Lipid Accumulation

Zhengwei Zhou, Biyao Luo, Xi Liu, Mimi Chen, Wenjun Lan, Juan L. Iovanna, Ling Peng*, and Yi Xia*

Chemical Communications, 2019, DOI: 10.1039/C9CC04084F

Download the article here:    2019 ChemCommun XIA


Dr. Ling Peng

Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM) UMR 7325, Equipe Labellisé par La Ligue, Marseille, France

Email: ling.peng@univ-amu.fr