Aspirin, lysine, mifepristone and doxycycline combined can effectively and safely prevent and treat cancer metastasis: prevent seeds from gemmating on soil

// Liyuan Wan 1,* , Haiyan Dong 1,* , Huo Xu 1 , Ji Ma 1 , Yewei Zhu 1 , Yusheng Lu 1 , Jichuang Wang 1 , Ting Zhang 1 , Tao Li 1 , Jingjing Xie 1 , Bo Xu 2 , Fangwei Xie 3 , Yu Gao 1 , Jingwei Shao 1 , Xiaohuang Tu 4 and Lee Jia 1 1 Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, China 2 Obstetrics and Gynecology, Fuzhou General Hospital, Fuzhou, China 3 Department of Medicine Oncology, East Hospital of Xiamen University, Fuzhou, China 4 Department of Surgery, East Hospital of Xiamen University, Fuzhou, China * These authors have contributed equally to this work Correspondence to: Lee Jia, email: // Keywords : cancer metastasis, cell adhesion molecules, drug combination, metastasis chemoprevention, HAMPT Received : August 07, 2015 Accepted : September 14, 2015 Published : October 08, 2015 Abstract Recent scientific advances have increased our understanding of the cancer metastatic complexities and provided further impetus for new combination therapies to prevent cancer metastasis. Here, we demonstrated that a combination (HAMPT) of aspirin, lysine, mifepristone and doxycycline can effectively and safely prevent cancer metastasis. The pharmaceutically-formulated HAMPT inhibited adhesion of cancer cells to either endothelial cells or extracellular matrix via down-regulating cell adhesion molecules ICAM-1 and α 4 -integrin. HAMPT inhibited the cloak effect by activated platelets on cancer cells, thereby interfering adhesion and invasion of cancer cells to the underlying stroma. At the effective concentration, HAMPT induced cancer cells into dormancy with minor inhibition on cell viability. Four-day pretreatment followed by 30-day oral administration of HAMPT (33.5-134 mg/kg) to the mice inoculated with cancer cells produced significant inhibition on cancer metastasis dose-dependently without marked side effects. Fifty-day rat toxicity study with HAMPT at doses (335-1340 mg/kg) 20-fold higher than its therapeutic dose produced no significant toxicity. Interestingly, the acute toxic death could not be reached at the maximum administrable dose (5 g/kg). This proof-of-concept study provides the first conceptual evidence that cancer metastasis can be controlled by using affordable old drugs to restrain circulating tumor cells from gemmating on the metastatic soil without the need for cytotoxicity.