Traditional Chinese medicine Danggui Buxue Tang inhibits colorectal cancer growth through induction of autophagic cell death.

Autor:	Chen ST; Department of Chinese Medicine, Taipei Buddhist Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan.; Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.; Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan., Lee TY; Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan., Tsai TH; Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.; Depatment of Chemical Engineering, National United University, Miaoli 36003, Taiwan., Huang YC; School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.; Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan ., Lin YC; Department of Medical Research, Mackay Memorial Hospital, New Taipei City 25160, Taiwan., Lin CP; Department of Medical Research, Mackay Memorial Hospital, New Taipei City 25160, Taiwan., Shieh HR; Department of Medical Research, Mackay Memorial Hospital, New Taipei City 25160, Taiwan., Hsu ML; Department of Medical Research, Mackay Memorial Hospital, New Taipei City 25160, Taiwan., Chi CW; Department of Medical Research, Mackay Memorial Hospital, New Taipei City 25160, Taiwan., Lee MC; Department of Research, Taipei Buddhist Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23141, Taiwan., Chang HH; School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, and Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung 40402, Taiwan.; Department of Chinese Medicine, China Medical University Hospital, Taichung 40402, Taiwan., Chen YJ; Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan .; Department of Medical Research, Mackay Memorial Hospital, New Taipei City 25160, Taiwan.; Department of Radiation Oncology, Mackay Memorial Hospital, Taipei 10449, Taiwan.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2017 Aug 03; Vol. 8 (51), pp. 88563-88574. Date of Electronic Publication: 2017 Aug 03 (Print Publication: 2017).
DOI:	10.18632/oncotarget.19902
Abstrakt:	Purpose: The induction of autophagic cell death is an important process in the development of anticancer therapeutics. We aimed to evaluate the activity of the ancient Chinese decoction Danggui Buxue Tang (DBT) against colorectal cancer (CRC) and the associated autophagy-related mechanism. Materials and Methods: CT26 CRC cells were implanted into syngeneic BALB/c mice for the tumor growth assay. DBT extracts and DBT-PD (polysaccharide-depleted) fractions were orally administered. The toxicity profiles of the extracts were analyzed using measurements of body weight, hemogram, and biochemical parameters. The morphology of tissue sections was observed using light and transmission electron microscopy. Western blotting and small interference RNA assays were used to determine the mechanism. Results: DBT-PD and DBT, which contained an equal amount of DBT-PD, inhibited CT26 syngeneic tumor growth. In the tumor specimen, the expression of microtubule-associated proteins 1A/1B light chain 3B (LC3B) was upregulated by DBT-PD and DBT. The development of autophagosomes was observed via transmission electron microscopy in tumors treated with DBT-PD and DBT. In vitro experiments for mechanism clarification demonstrated that DBT-PD could induce autophagic death in CT26 cells accompanied by LC3B lipidation, downregulation of phospho-p70 s6k , and upregulation of Atg7. RNA interference of Atg7, but not Atg5, partially reversed the effect of DBT-PD on LC3B lipidation and expression of phospho-p70 s6k and Atg7. The changes in ultrastructural morphology and LC3B expression induced by DBT-PD were also partially blocked by the knockdown of Atg7 mRNA. Conclusion: DBT induced autophagic death of colorectal cancer cells through the upregulation of Atg7 and modulation of the mTOR/p70 s6k signaling pathway. Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.
Databáze:	MEDLINE
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