Search

Ginsenoside (G-CK) has good chemo preventive and anticancer effects. However, its antimetastatic effects and underlying mechanisms on cervical cancer (CC) are still not clear. This study found that both G-CK and DDP inhibited the proliferation of HeLa cells in a concentration-dependent manner, and the combination blocked cell growth and colony-forming ability, and inhibited cell migration and EMT processes. The signature molecule of EMT, E-cadherin, was up-regulated, and both N-cadherin and vimentin were down-regulated and cell migration was affected through inhibition of RAS/MEK/ERK and PI3K/AKT signaling pathways. DDP could induce oxidative stress damage in HEK293 cells, as evidenced by the accumulation of ROS, decrease in GSH levels and oxidative stress antioxidant enzymes (CAT, SOD and GSH-Px) and increase in GSSG and MDA levels, which proved that G-CK exerted inhibitory on HeLa cell proliferation and EMT in combination with traditional anti-cancer drug and protected normal cells from DDP-induced oxidative stress damage.

Several experimental and biological studies have emphasized the tumor suppression efficacy and low toxicity of Apigenin (API); however, its exact underlying mechanism on human endometrial carcinoma Ishikawa cell line (EC) is still unknown. We found that API could inhibit the proliferation of Ishikawa cells at IC50 of 45.55 μM, arrest the cell cycle at G2/M phase, induce apoptosis by inhibiting Bcl-xl and increasing Bax, Bak and Caspases. Further, API could induce apoptosis by activating the endoplasmic reticulum (ER) stress pathway by increasing the Ca2+, ATF4, and CHOP. It could impede cell migration and invasion through PI3K-AKT-GSK-3β signaling pathway, preventing wound healing, restraining cells migration from the upper chamber to the lower chamber. This study demonstrated that API can be used as a promising dietary supplement and an adjuvant chemotherapeutic agent for cancer treatment.

Recent advances in cellular markers (cell signaling pathways) indicate their potency in disease progression and also provide therapeutic benefits to biomedicine. Interestingly, in normal functioning cells, endoplasmic reticulum (ER), a membranous intracellular organelle is well characterized for inextricable links in cellular homeostasis through protein synthesis regulation destined for cell-to-cell communication. However, several genetic and ecological aberration impede their vast interplay and reason the buildup of outspread or misfolded proteins, spontaneously leading to multifaceted and dynamic ER stress reaction to escape instant cell dysfunction to trigger cell death which are the key contributors for the development of epidemiological disorders linked with cancer, neurodegeneration, diabetes, viral infections, and other chronic ailments. Consequently, there is great concern in targeting components of specific ER stress signaling pathways, cooperatively recognized as the unfolded protein response (UPR) and its branches in the regime of combating these ER-stress linked pathologies. The significance of natural products in contemporary medication continues to be of a great importance for the generation of novel lead compounds. UPR and its sensors are the targets of several natural compounds for balancing the ER homeostasis with an intent to treat ER stress-related diseases. Here, we focus on several natural products as therapeutic interventions to target ER stress signaling pathways. We mainly updated the information on the ER and its functions responsible for epidemiologically-relevant diseases, as well as extended it to the crosstalk with complex signal transduction pathways related to the ER stress response. Additionally, we also highlighted integrated insights on natural compounds derived ER response biomarkers which can be targeted for therapeutic purposes to deal with unmet biomedical requirements.

Endometrial cancer (EC) associated with endogenous hormone metabolism, obesity, diabetes, and inappropriate dietary habits has shown a rising trend in recent years. Various therapeutics methods including dietary approaches (vital phytochemicals) offer healthy and nontoxic strategies against cancer. To date, 6-shogaol as one of the antitumor phytochemicals remains unexplored against human endometrial cancer cells. In our study, 6-shogaol obtained from Zingiber officinale rhizomes separated and purified by HPLC, LC-MS/MS, and NMR respectively could inhibit Ishikawa cell proliferation at IC50 (24.91 μM) with the arrested cell cycle in the G2/M phase. Moreover, it promoted apoptosis, as a result, triggered ROS production, then activated key ER response biomarkers in Ishikawa cell associated with mitochondria, and ultimately regulated related genes and proteins in vitro and in vivo. Therefore, 6-shogaol can be used as a promising natural compound endowed with potential benefits for cancer treatment and/or prevention at large and EC in particular.