A marine anthraquinone SZ-685C overrides adriamycin-resistance in breast cancer cells through suppressing Akt signaling.
Breast cancer remains a major health problem worldwide. While chemotherapy represents an important therapeutic modality against breast cancer, limitations in the clinical use of chemotherapy remain formidable because of chemoresistance. The HER2/PI-3K/Akt pathway has been demonstrated to play a causal role in conferring a broad chemoresistance in breast cancer cells and thus justified to be a target for enhancing the effects of anti-breast cancer chemotherapies, such as adriamycin (ADR). Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance are urgently needed for the treatment of breast cancer. In this context, SZ-685C, an agent that has been previously shown, as such, to suppress Akt signaling, is expected to increase the efficacy of chemotherapy. Our current study investigated whether SZ-685C can override chemoresistance through inhibiting Akt signaling in human breast cancer cells. ADR-resistant cells derived from human breast cancer cell lines MCF-7, MCF-7/ADR and MCF-7/Akt, were used as models to test the effects of SZ-685C. We found that SZ-685C suppressed the Akt pathway and induced apoptosis in MCF-7/ADR and MCF-7/Akt cells that are resistant to ADR treatment, leading to antitumor effects both in vitro and in vivo. Our data suggest that use of SZ-685C might represent a potentially promising approach to the treatment of ADR-resistant breast cancer.
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Xun
X
Zhu
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Zhenjian
Z
He
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Jueheng
J
Wu
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Jie
J
Yuan
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Weitao
W
Wen
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Yiwen
Y
Hu
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou 510080, China.|Department of Cardiology, The First People's Hospital of Zigong, 42 Shangyihao Road I, Zigong 643000, China.
Yi
Y
Jiang
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Cuiji
C
Lin
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.
Qianhui
Q
Zhang
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.
Min
M
Lin
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.
Henan
H
Zhang
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.
Wan
W
Yang
Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Hong
H
Chen
Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Lili
L
Zhong
Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Zhigang
Z
She
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.
Shengping
S
Chen
Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Yongcheng
Y
Lin
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.|Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Mengfeng
M
Li
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D000880:Anthraquinones; D047428:Protein Kinase Inhibitors; C569938:SZ 685C; D004317:Doxorubicin; D051057:Proto-Oncogene Proteins c-akt