Antcin K, an active triterpenoid from the fruiting bodies of basswood cultivated Antrodia cinnamomea, induces mitochondria and endoplasmic reticulum stress-mediated apoptosis in human hepatoma cells

Abstract

Liver cancer is the second leading cause of cancer deaths in Taiwan as per the 2011 statistics and ranks fourth in cancer-related mortality in the world. Recent researches have shown that Antrodia cinnamomea, a Taiwan-specific medicinal mushroom, has biological activities, including hepatoprotection, anti-inflammation, antihepatitis B virus activity, and anticancer activity. In the present study, the antiproliferative activity and molecular mechanisms of antcin K, the most abundant ergostane triterpenoid from the fruiting bodies of basswood cultivated A. cinnamomea, were investigated using human hepatoma Hep 3B cells. The results showed that antcin K effectively reduced Hep 3B cells viability within 48 hours. Antcin K induced phosphatidylserine exposure, chromatin condensation, and DNA damage, but did not significantly increase autophagosome content or cause cell expansion and cell lysis. Thus, the principal mode of Hep 3B cells death induced by antcin K was apoptosis, rather than autophagy or necrosis. In-depth investigation of the molecular mechanisms revealed that antcin K first promoted reactive oxygen species generation and adenosine triphosphate depletion, leading to endoplasmic reticulum stress and resulting in mitochondrial membrane permeability changes. After losing the mitochondrial membrane potential, caspase-independent and caspase-dependent apoptosis-related proteins were released, including HtrA2, apoptotic-induced factor, endonuclease G, and cytochrome c. Cytochrome c activated caspase-9 and caspase-3, and cut downstream protein PARP, ultimately leading to cell apoptosis. These results suggested that antcin K induced mitochondrial and endoplasmic reticulum stress-mediated apoptosis in human hepatoma cells. Coupled with these findings, antcin K has a potential to be a complementary agent in liver cancer therapy.

Chemical evaluation and cytotoxic mechanism investigation of Clinacanthus nutans extract in lymphoma SUP‐T1 cells

“…Annexin V is one of the calcium-binding protein located on the inner cell membrane, and it is inverted into the outer membrane after apoptosis induction. 25 Our results demonstrate that 37.5 and 50 μg/mL MHA treatment induced annexin V protein overexpression in SUP-T1 lymphoma cells. Figure 4 presents clearly apoptotic circumstances after MHA treatment for 24 hr in human lymphoma cells.…”

“…In order to investigate MHA induce apoptosis in SUP‐T1 lymphoma cells, the annexin V‐FITC protein expression was detected by flow cytometry. Annexin V is one of the calcium‐binding protein located on the inner cell membrane, and it is inverted into the outer membrane after apoptosis induction . Our results demonstrate that 37.5 and 50 μg/mL MHA treatment induced annexin V protein overexpression in SUP‐T1 lymphoma cells.…”

Antcin-A Modulates Epithelial-to-Mesenchymal Transition and Inhibits Migratory and Invasive Potentials of Human Breast Cancer Cells via p53-Mediated miR-200c Activation

“…The anti-cancer properties of A. cinnamomea have been attributed to its unique composition of phytochemicals such as antroquinonols, antcins, and antrodins [12-15, 23, 24]. Among them, the antcins (ATA, antcin-B, antcin-C, antcin-D, antcin-E, antcin-F, antcin-G, antcin-H, antcin-I, antcin-K, and antcin M) are steroid-like compounds that exert various biological activities including, anti-inflammation [16,25], hepatoprotection [26][27][28], anti-aging [29], anti-cancer [30][31][32][33], and anti-metastasis [34]. We have previously reported that ATA isolated from the fruiting bodies of A. cinnamomea inhibits inflammation in lung cells via mimicking a glucocorticoid receptor agonist, and this effect was highly comparable with synthetic steroids, such as cortisone and dexamethasone [16].…”

Biotransformation of Ergostane Triterpenoid Antcin K from Antrodia cinnamomea by Soil-Isolated Psychrobacillus sp. AK 1817

“…Due to the abundance of antcin K in wood-cultivated, as well as in dish-cultivated, A. cinnamomea, many bioactivities of antcin K have been found [3][4][5][6][7][8]. In contrast, few studies on antcamphin E and antcamphin F have been reported, due to their rarity.…”