4.6 Article

Antrodia salmonea induces apoptosis and enhances cytoprotective autophagy in colon cancer cells

Journal

AGING-US
Volume 13, Issue 12, Pages 15964-15989

Publisher

IMPACT JOURNALS LLC

Keywords

Antrodia salmonea; colon cancer; apoptosis; autophagy; ROS

Funding

  1. Ministry of Science and Technology [MOST-109-2320-B-039-057-MY3, MOST-107-2320-B-039-013-MY3]
  2. China Medical University, Taiwan [CMU107-TU-12, CMU108MF-19, CMU108-MF-80]
  3. Taiwan and Chinese Medicine Research Center, China Medical University from the Featured Areas Research Center Program within the Ministry of Education (MOE) [CMRC-CHM-1]
  4. Asia University

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The traditional Chinese medicinal fungus Antrodia salmonea (AS) exhibits significant anti-cancer activity in colon cancer cells by inducing apoptosis and autophagy mechanisms mediated through reactive oxygen species (ROS).
A traditional Chinese medicinal fungus, Antrodia salmonea (AS), with antioxidant properties is familiar in Taiwan but anti-cancer activity of AS in human colon cancer is ambiguous. Hence, we explored the anti-cancer activity of AS in colon cancer cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that AS showed a remarkable effect on cell viability in colon cancer cells; SW620, HCT116, and HT29. Annexin V/propidium iodide (PI) stained cells indicated that AS induced both early/late apoptosis in SW620 cells. Additionally, cells treated with AS induced caspase-3 activation, poly (ADP-ribose) polymerase (PARP) cleavage, mitochondrial dysfunction, and Bcl-2 associated X (Bax)/B-cell lymphoma (Bcl-2) dysregulation. Microtubule- associated protein 1A/1B-light chain 3B (LC3-II) accumulation, sequestosome 1 (p62/SQSTM1) activation, autophagy related 4B cysteine peptidase (ATG4B) inactivation, acidic vesicular organelles (AVOs) formation, and Beclin-1/Bcl-2 dysregulation revealed that AS-induced autophagy. Interestingly, cells pretreated with 3-methyladenine (3-MA) strengthened AS-induced caspase-3/apoptosis. Suppression of apoptosis by z-Val-Ala-Asp fluoromethyl ketone (Z-VAD-FMK) did not however block AS-induced autophagy, suggesting that autophagy was not attenuated by the AS-induced apoptosis. Application of N-acetylcysteine (NAC) prevented AS-induced cell death, caspase-3 activation, LC3-II accumulation, and AVOs formation, indicating that AS-induced apoptosis and autophagy was mediated by reactive oxygen species (ROS). Furthermore, AS-induced cytoprotective autophagy and apoptosis through extracellular signal-regulated kinase (ERK) signaling cascades. Moreover, in vivo data disclosed that AS inhibited colitis-associated tumorigenesis in azoxymethane (AOM)-dextran sodium sulphate (DSS)-treated mice. For the first time, we report the anti-cancer properties of this potentially advantageous mushroom for the treatment of human colon cancer.

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