A Distinctive Pattern ofBeauveria bassiana-biotransformed Ginsenoside Products Triggers Mitochondria/FasL-mediated Apoptosis in Colon Cancer Cells

Abstract

Ginseng is one of the most commonly used adaptogens. Transformation into the minor ginsenosides produces compounds with more effective action. Beauveria bassiana, a teleomorph of Cordyceps bassiana, is a highly efficient producer of mammalian steroids and produces large amounts of sugar-utilizing enzymes. However, the fermentation of steroid glycosides in ginseng with B. bassiana has never been studied. Thus, we evaluated the bioconversion of the major ginsenosides in white ginseng by B. bassiana. Interestingly, B. bassiana increased the total amount of protopanaxadiols and hydrolyzed Rb1 into minor ginsenosides, exhibiting high levels of Rd and Rg3, as well as moderate levels of Rb2 and Rc analyzed by high-performance liquid chromatography coupled with evaporative light-scattering detection. The β-glucosidase activity was highly increased, which led to the selective elimination of sugar moiety at the 20-C position of Rb1 to Rd, followed by Rg3. Rb2 and Rc accumulated because of the minimal activities of α-L-arabinopyranosidase and α-L-arabinofuranosidase, respectively. The fermentation product exerted dose-dependent cytotoxicity in HCT-15 cells, which are resistant to ginseng. The product, but not white ginseng, exhibited apoptotic effects via the Fas ligand and caspase 8/9. This study demonstrates for the first time that the B. bassiana-fermented metabolites have potent apoptotic activity in colon cancer cells, linking to a therapeutic use.

Dose dependent effects of cadmium on tumor angiogenesis

“…Stress activated JNK is associated with nuclear translocation of activator protein-1 (AP-1) [ 83 ], which promotes the transcriptional expression of Bax and Fas ligand (FasL) [ 83 , 84 ]. Bax-facilitated release of cytochrome c and FasL-engaged Fas mediate apoptosis via the intrinsic mitochondrial pathway [ 84 – 86 ]. In the presence of NF-κB inhibitor, low-dose Cd increased JNK phosphorylation, which resulted in a substantial decrease in viable cell count [ 67 , 87 ].…”

Tianfoshen oral liquid: a CFDA approved clinical traditional Chinese medicine, normalizes major cellular pathways disordered during colorectal carcinogenesis

“…Previously, abnormal expression and activity of anti-apoptosis-related proteins and genes including the inhibitor of apoptosis protein family, the Bax family and the BH3-only protein family has been associated with poor prognosis and drug resistance in CRC [38, 39]. Composite compounds and extractive fractions of Radix Panacis Quinquefolii and Venenum Bufonis can induce the apoptosis of CRC cells in vitro and in vivo [40, 41]. Additionally, quercetin, as an active compound shared by Radix Asparagi , Radix Actinidia chinensis Planch .…”

Phytoadaptogens in the Tumours Biotherapy and Geriatrics (Part 2)

“…Вместе с тем причиной индукции апоптоза с помощью ФА может быть запуск митохондриальных нарушений. Некоторые гинзенозиды (Rh2, Rg3) способствуют апоптической смерти клеток гепатомы человека (линии SK-HEP-1), рака яичника (линия HO-8910), рака толстой кишки с помощью усиления деполяризации мембран митохондрий с последующим выбросом цитохрома с транслокацией белка Bax, а также подавления белков семейства фосфатидилинозитол-3-киназы (PI3K / Akt) и ингибитора белков апоптоза (IAP), запуская активацию каспаз 3 и 9 [14,15]. Наряду с этим возможно воздействие ФА на апоптоз in vivo.…”