New bis(hydroxymethyl) alkanoate curcuminoid derivatives exhibit activity against triple-negative breast cancer in vitro and in vivo.
Novel bis(hydroxymethyl) alkanoate curcuminoid derivatives were designed, synthesized and screened for in vitro antiproliferative and in vivo antitumor activity. Selected new compound 9a and curcumin were further evaluated for inhibitory activity against ER+/PR+breast cancer (MCF-7, T47D), HER 2+breast cancer (SKBR3, BT474, and MDA-MB-457) and triple negative breast cancer (TNBC) (HS-578T, MDA-MB-157, and MDA-MB-468) cell lines. In addition, compound 9a was evaluated in the MDA-MB-231 xenograft nude mice model. Compound 9a exhibited greater inhibitory activity than curcumin against TNBC cells and also demonstrated significant inhibitory activity against doxorubicin-resistant MDA-MB-231 cells, with ten-fold higher potency than curcumin. Furthermore, when evaluated against the MDA-MB-231 xenograft nude mice model, compound 9a alone was ten-fold more potent than curcumin. Moreover, synergistic activity was observed when 9a was used in combination with doxorubicin against MDA-MB-231 breast cancer cells.
Chinese Medicinal Research and Development Center, China Medical University and Hospital, Taichung 404, Taiwan; School of Pharmacy, China Medical University, Taichung 404, Taiwan.
Min-Tsang
MT
Hsieh
Chinese Medicinal Research and Development Center, China Medical University and Hospital, Taichung 404, Taiwan.
Ling-Chu
LC
Chang
School of Pharmacy, National Cheng Kung Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Hsin-Yi
HY
Hung
School of Pharmacy, China Medical University, Taichung 404, Taiwan.
Hui-Yi
HY
Lin
School of Pharmacy, China Medical University, Taichung 404, Taiwan.
Mei-Hui
MH
Shih
China Medical University and Hospital, Taichung 404, Taiwan.
Chang-Hai
CH
Tsai
Chinese Medicinal Research and Development Center, China Medical University and Hospital, Taichung 404, Taiwan; School of Pharmacy, China Medical University, Taichung 404, Taiwan. Electronic address: sckuo@mail.cmu.edu.tw.
Sheng-Chu
SC
Kuo
Chinese Medicinal Research and Development Center, China Medical University and Hospital, Taichung 404, Taiwan; Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States. Electronic address: khlee@unc.edu.
Kuo-Hsiung
KH
Lee
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D013329:Structure-Activity Relationship; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D003474:Curcumin
Antiproliferative agents; Antitumor agents; Bis(hydroxymethyl) alkanoate curcuminoids; Curcumin; Triple-negative breast cancer