title: Apoptotic effects of extract from Cnidium monnieri (L.) Cusson by adenosine monosphosphate-activated protein kinase-independent pathway in HCT116 colon cancer cells.
abstract: Colon cancer, a common malignancy, can occur due to poor eating habits and increasing age. Consequently, careful regulation of eating habits may serve as a possible method for preventing the occurrence or progression of colon cancer. Extracts of the fruit of Cnidium monnieri (L.) Cusson are well‑known as an effective herbal medicine for the treatment of pain in female genitalia and carbuncle. However, there have been no studies on the apoptotic effects of Cnidium monnieri (L.) Cusson (CME). Adenosine monophosphate‑activated protein kinase (AMPK), the major regulator of energy metabolism, is activated by metabolic stress, including hypoxia and glucose deprivation. Activation of AMPK inhibits cell proliferation and induces apoptosis through the inhibition of phosphorylated (p)‑Akt and control of B‑cell lymphoma 2 (Bcl‑2) family members. The pro‑apoptotic proteins Bcl‑2‑associated X protein (Bax) and Bcl‑2‑homologous antagonist killer (Bak), are activated by their translocation to mitochondria from the cytosol. Translocation of Bax/Bak induces outer membrane permeabilization and is likely to lead to apoptosis through cytochrome C release and caspase activity. In the present study, the apoptotic effects and influence on mitochondria‑mediated apoptotic proteins of CME in HCT116 cells were assessed. We hypothesized that CME may have an effect on the inhibition of p‑Akt in an AMPK‑independent pathway. The present study demonstrated that CME induced the release of LDH and apoptosis through its inhibition of p‑Akt to control Bcl‑2 and activate Bax and Bak. Co‑treatment with CME and AMPK inhibitors showed that CME‑induced apoptosis does not occurr through a AMPK‑dependent pathway. Therefore, the present study determined, for the first time, that CME induced apoptosis as a result of causing metabolic stresses due to directly regulation of the de‑phosphorylation of Akt, whereas it did not control the AMPK-dependent pathway in HCT116 colon cancer cells.
authors.affiliation: Department of Biological Sciences and Biotechnology, College of Life Science and Nanotechnology, Hannam University, Yuseong‑gu, Daejeon 305‑811, Republic of Korea.
authors.forename: Eun Gyeong
authors.initials: EG
authors.lastname: Lim
authors.affiliation: Department of Biological Sciences and Biotechnology, College of Life Science and Nanotechnology, Hannam University, Yuseong‑gu, Daejeon 305‑811, Republic of Korea.
authors.forename: Guen Tae
authors.initials: GT
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences and Biotechnology, College of Life Science and Nanotechnology, Hannam University, Yuseong‑gu, Daejeon 305‑811, Republic of Korea.
authors.forename: Se Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Biongene, Chongro‑gu, Seoul 110‑521, Republic of Korea.
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences and Biotechnology, College of Life Science and Nanotechnology, Hannam University, Yuseong‑gu, Daejeon 305‑811, Republic of Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D031048:Cnidium / Q000737:chemistry*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases