Aqueous Oldenlandia diffusa extracts inhibits colorectal cancer cells via activating AMP-activated protein kinase signalings.
Here we evaluated the anti-cancer activity of aqueous Oldenlandia diffusa (OD) extracts (ODE) in colorectal cancer (CRC) cells. We showed that ODE exerted potent anti-proliferative, cytotoxic and pro-apoptotic activities against a panel of established CRC lines (HCT-116, DLD-1, HT-29 and Lovo) and primary (patient-derived) human CRC cells. ODE activated AMP-activated protein kinase (AMPK) signaling, which led to subsequent mTORC1 inhibition and Bcl-2/HIF-1α downregulation in CRC cells. In ODE-treated CRC cells, AMPKα1 formed a complex with p53. This might be important for p53 activation and subsequent cancer cell apoptosis. Inhibition of AMPK signaling, though dominant negative (dn) mutation or shRNA/siRNA knockdown of AMPKα1 attenuated ODE-exerted CRC cytotoxicity. In vivo, i.p. administration of ODE inhibited HCT-116 xenograft tumor growth in SCID mice. In addition, AMPK activation, mTORC1 inhibition and p53 activation were observed in ODE-treated HCT-116 xenograft tumors. These results suggest that ODE inhibits CRC cells in vitro and in vivo, possibly via activation of AMPK-dependent signalings.
Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Department of Medical Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, Jiangsu, China.
Pei-Hua
PH
Lu
Department of Medical Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, 215300, Jiangsu, China.
Min-Bin
MB
Chen
Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China.
Chao
C
Ji
Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Wen-Ting
WT
Li
Department of Traditional Chinese Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Mu-Xin
MX
Wei
Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Mian-Hua
MH
Wu
D055372:AMP-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D032067:Oldenlandia; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D010936:Plant Extracts; D055372:AMP-Activated Protein Kinases
AMP-activated protein kinase (AMPK); Oldenlandia diffusa (OD) extracts (ODE); colorectal cancer (CRC); p53 and mammalian target of rapamycin (mTOR)