The anticancer effect of extract of medicinal mushroom Sanghuangprous vaninii against human cervical cancer cell via endoplasmic reticulum stress-mitochondrial apoptotic pathway

Sanghuangprous vaninii (Ljub.) L.W. Zhou & Y.C. Dai, known as "Sanghuang" in China, is mainly distributed in the northeast of China. As a traditional medicinal mushroom, "Sanghuang" is medicinally used for resolving the symptoms of gynecological tumors including vaginal bleeding, leucorrhea, abdominal pain and abdominal mass. This mushroom is potential for gynecological cancers therapy. However, there is a lack of scientific evidence on its anti-tumor activity against human cervical cancer, the most common gynecological cancer.To identify the anti-tumor potential of the extract of Sanghuangprous vaninii (ESV) on human cervical cancer SiHa cells, and explore detailed mechanisms of ESV inducing cancer cell death.The anti-proliferation effects were evaluated by Cell Counting Kit-8 (CCK8) assay. Transmission electron microscope was applied to determined the cellular ultrastructure changes. The cell cycle distribution, quantification of apoptotic cells, mitochondrial transmembrane potential, reactive oxygen species (ROS) level, and cytosolic calcium level were determined by flow cytometer. Western blot analysis was used to explore the alterations in the expression levels of endoplasmic reticulum stress-marked and apoptosis-related proteins. The in-vivo anti-tumor effect was identified by mouse xenograft model.ESV significantly inhibited the proliferation of SiHa cells in vivo and vitro. Blocking cell cycle and causing cell apoptosis contributed to cell death induced by ESV. Mechanistically, ESV induced endoplasmic reticulum stress evidenced by the elevated expressions of GRP78 and CHOP, which accompanied by the release of calcium (Ca2+). The Ca2+ overload and oxidative stress facilitated the collapse of mitochondrial membrane potential and subsequently activated caspase-3 and -9, which eventually lead to cell apoptosis.Our results revealed that Sanghuangprous vaninii was effective against human cervical cancer SiHa cells in vitro and vivo. There is a promising potential that Sanghuangprous vaninii might be a candidate for cervical cancer therapy.