Polyporenic acid C induces caspase‐8‐mediated apoptosis in human lung cancer A549 cells

Abstract

Lung cancer continues to be the leading cause of cancer-related mortality worldwide. This warrants the search for new and effective agents against lung cancer. We and others have recently shown that lanostane-type triterpenoids isolated from the fungal species Poria cocos (P. cocos) can inhibit cancer growth. However, the mechanisms responsible for the anticancer effects of these triterpenoids remain unclear. In this study, we investigated the effect of polyporenic acid C (PPAC), a lanostane-type triterpenoid from P. cocos, on the growth of A549 nonsmall cell lung cancer cells (NSCLC). The results demonstrate that PPAC significantly reduced cell proliferation via induction of apoptosis as evidenced by sub-G1 analysis, annexin V-FITC staining, and increase in cleavage of procaspase-8, -3, and poly(ADP-ribose)-polymerase (PARP). However, unlike our previously reported lanostane-type triterpenoid, pachymic acid, treatment of cells with PPAC was not accompanied by disruption of mitochondrial membrane potential and increase in cleavage of procaspase-9. Further, PPC-induced apoptosis was inhibited by caspase-8 and pan caspase inhibitors but not by a caspase-9 inhibitor. Taken together, the results suggest that PPAC induces apoptosis through the death receptor-mediated apoptotic pathway where the activation of caspase-8 leads to the direct cleavage of execution caspases without the involvement of the mitochondria. Furthermore, suppressed PI3-kinase/Akt signal pathway and enhanced p53 activation after PPAC treatment suggests this to be an additional mechanism for apoptosis induction. Together, these results encourage further studies of PPAC as a promising candidate for lung cancer therapy.

Triterpenes from Poria cocos suppress growth and invasiveness of pancreatic cancer cells through the downregulation of MMP-7

“…As previously demonstrated P. cocos triterpenes: PA, DPA and PPAC inhibited growth of human breast cancer, lung cancer and prostate cancer cells (11)(12)(13)22). To evaluate whether these triterpenes also affect growth of different human pancreatic cancer cell lines, Panc-1, MiaPaca-2, AsPc-1 and BxPc-3 cells were treated with PTE (0-80 µg/ml) for 24 and 48 h and the proliferation determined as described in Materials and methods.…”

“…Poria cocos (also known as Wolfiporia extensa) is a medicinal mushroom in the Polyporaceae family that grows in pine trees and its sclerotium is widely used in traditional Asian medicine for its sedative, diuretic, digestive and tonic effects (6)(7)(8). Although the anticancer activity of polysaccharides extracted from P. cocos is associated with the stimulation of immune response and these polysaccharides significantly enhance immunopotentiation (9), triterpenes isolated from P. cocos have a direct inhibitory effect on cancer cells through a variety of mechanisms including inhibition of cell proliferation, induction of apoptosis and suppression of invasive behavior (10)(11)(12)(13)(14)(15)(16). However the effect of triterpenes from P. cocos against pancreatic cancer remains to be evaluated and the mechanism determined.…”

Medicinal properties of fungi occurring on Betula sp. trees. A review

“…After examining its effect on nonsmall lung cancer cells (A549 cells), it appeared to satisfactorily inhibit cell division depending on dosage: 60 μM of the acid reduced cell proliferation by 50%, 200 μM did by as much as 90%. Moreover, it induces apoptotic processes as early as in the caspase-mediated stages [15].…”

“…Many undervalued species of polyporoid fungi growing mainly on birch that show medicinal properties can be found in Poland. Such compounds as polysaccharides [2][3][4][5][6][7][8], polyphenols [6,9], triterpenes [6,10,11] which are contained in them demonstrate positive influence on the human organism; they mainly exhibit anticancer [4,5,9,[12][13][14][15], anti-inflammatory [16,17], anti-bacterial [18] and immunostimulant [2,7,19] activity.…”

Rp-HPLC-Dad Determination of Six Triterpenes in a Herbal Tonic Hoelen

“…[2][3][4][5][6] To date, a total of 66 triterpenes that were isolated from Hoelen have been researched, and triterpenes were suggested to be the major medicinal components contributing to its major bioactivities. [7][8][9][10] Furthermore, to assess and control the quality of the tonic, several methods that revolved around the use of high performance liquid chromatography (HPLC) have been studied. These included HPLC fingerprint and HPLC in tandem with DAD or mass spectrometry (MS).…”