Cytotoxic Constituents from the Sclerotia of Poria cocos against Human Lung Adenocarcinoma Cells by Inducing Mitochondrial Apoptosis

Abstract

Previous studies have revealed the antitumor potential of Poria cocos Wolf against a broad spectrum of cancers. However, the biological activity of P. cocos against lung cancer, which is known as the leading cause of cancer mortality worldwide, and its underlying chemical and molecular basis, remain to be investigated. We aimed to evaluate the in vitro cytotoxicity of P. cocos toward human lung adenocarcinoma cells with different p53 statuses, to identify the bioactive constituents of P. cocos, and explicate the molecular mechanisms underlying the cytotoxicity of these constituents in human lung adenocarcinoma cells. An EtOH extract of the sclerotia of P. cocos exhibited cytotoxicity toward four human lung cancer cell lines: A549, H1264, H1299, and Calu-6, regardless of their p53 status. Chemical investigation of the extract resulted in the isolation of two triterpenoids, dehydroeburicoic acid monoacetate (1) and acetyl eburicoic acid (4); a sterol, 9,11-dehydroergosterol peroxide (2); and a diterpenoid, dehydroabietic acid (3). All of the isolated compounds were cytotoxic to the lung adenocarcinoma cell lines, exhibiting IC50 values ranging from 63.6 μM to 171.0 μM at 48 h of treatment. The cytotoxicity of the extract and the isolated compounds were found to be mediated by apoptosis, and accompanied by elevated Bax expression and/or Bcl-2 phosphorylation along with caspase-3 activation. Our data demonstrate that the sclerotium of P. cocos and its four bioactive constituents (1–4) exert cytotoxicity against human lung adenocarcinoma cells, regardless of their p53 status, by inducing apoptosis associated with mitochondrial perturbation, and proposing the potential to employ P. cocos in the treatment of lung cancer.

Benzyl salicylate from the stems and stem barks of Cornus walteri as a nephroprotective agent against cisplatin-induced apoptotic cell death in LLC-PK1 cells

“…walteri stems and stem barks collected from Jeju Island, Korea were extracted with 80% aqueous MeOH under reux, and then evaporated under a vacuum to obtain a MeOH crude extract, which was subsequently solvent-fractionated with hexane, CHCl 3 , and n-BuOH, yielding soluble fractions of each solvent. Signicant spots were detected in the hexane-soluble fraction aer TLC analysis, and the hexane-soluble fraction was subjected to repeated column chromatography and HPLC purication, which resulted in the isolation of 15 compounds, including seven triterpenoids (1-7), ve steroids (8)(9)(10)(11)(12), two diterpene analogs (13 and 14), and one phenolic compound (15). Based on a comparison of their spectroscopic (including 1 H and 13 C NMR) and physical data with previously reported values and LC/MS analyses, the chemical structures of all the isolates were determined and identied as: leucophyllone (1), 11 3-O-acetylbetulin (2), 20 betulinic acid methyl ester (3), 21 lupenone (4), 22 methyl 3-O-acetylbetulinate (5), 23 lupeol (6), 24 betulinic acid (7), 25 6b-hydroxysitostenone (8), 26 sitostenone (9), 27 5astigmast-3,6-dione (10), 28 3b-sitostanol (11), 29 6a-hydroxy-bsitostenone (12), 30 norphytan (13), 31 phytone 14, 32 and benzyl salicylate (15) 33 (Fig.…”

“…In our continued quest to discover biologically novel natural products from a variety of Korean natural resources, [13][14][15][16][17] our group has explored the potential bioactive constituents of C. walteri. 11,18,19 Our previous studies reported that the MeOH extract of the stems and stem barks of C. walteri are signicantly cytotoxic.…”

“…11,18,19 These ndings were our motivation to further investigate potential bioactive constituents in the MeOH extract of C. walteri. Hence, in this study, we performed advanced phytochemical analyses to examine the potential nephroprotective constituents of the MeOH extract of C. walteri, leading to the successful isolation of 15 compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). We therefore report the isolation and structural elucidation of these compounds and the evaluation of their protective effects against cisplatin-induced nephrotoxicity in renal tubular epithelial (LLC-PK1) cells.…”

Aviculin Isolated from Lespedeza cuneata Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway

“…As part of the continuing research into bioactive compounds from Korean medicinal plant sources [13][14][15][16][17], the MeOH extract of the aerial portion of L. cuneata was found to exhibit cytotoxic effects on human ovarian carcinoma cells [5]. In our recent study, bioassay-guided fractionation of the MeOH extract using repeated chromatography resulted in the isolation of (−)-9 -O-(α-l-rhamnopyranosyl)lyoniresinol, which inhibited the proliferation of A2780 human ovarian carcinoma cells through the induction of apoptosis [5].…”

(–)-Catechin-7-O-β-d-Apiofuranoside Inhibits Hepatic Stellate Cell Activation by Suppressing the STAT3 Signaling Pathway

“…As part of our continuing projects to explore biologically active, unique natural products from diverse natural sources [18][19][20][21][22], we recently took note of Ulmus davidiana var. japonica, the root barks of which have been used as a Korean traditional medicine for various therapeutic purposes including gastroenteric disorders and inflammatory disorders [23][24][25][26].…”