Natural Polyphyllins (I, II, D, VI, VII) Reverses Cancer Through Apoptosis, Autophagy, Mitophagy, Inflammation, and Necroptosis

Abstract

Cancer is the second leading cause of mortality worldwide. Conventional therapies, including surgery, radiation, and chemotherapy, have limited success because of secondary resistance. Therefore, safe, non-resistant, less toxic, and convenient drugs are urgently required. Natural products (NPs), primarily sourced from medicinal plants, are ideal for cancer treatment because of their low toxicity and high success. NPs cure cancer by regulating different pathways, such as PI3K/AKT/mTOR, ER stress, JNK, Wnt, STAT3, MAPKs, NF-kB, MEK-ERK, inflammation, oxidative stress, apoptosis, autophagy, mitophagy, and necroptosis. Among the NPs, steroid saponins, including polyphyllins (I, II, D, VI, and VII), have potent pharmacological, analgesic, and anticancer activities for the induction of cytotoxicity. Recent research has demonstrated that polyphyllins (PPs) possess potent effects against different cancers through apoptosis, autophagy, inflammation, and necroptosis. This review summarizes the available studies on PPs against cancer to provide a basis for future research.

Transforming Cold Tumors into Hot Ones with a Metal–Organic Framework-Based Biomimetic Nanosystem for Enhanced Immunotherapy

“…Based on the affinity score (Table S1), PPI could fit into the binding site of NF-κB1 (PDB: 1MDI) (Figure E), indicating that PPI binding can enhance the activity of NF-κB1. Given the cross-talk between the NF-κB and cGAS/STING pathways, , we proposed that PPI could exert antitumor immune responses through the cGAS/STING pathway, and a series of experiments were conducted in vitro and in vivo.…”

“…Polyphyllin I (PPI), one of the polyphyllins derived from Paris polyphylla, is a promising anticancer agent, although the underlying mechanisms have not yet been deciphered. − Yu et al summarized that polyphyllin VII, another critical component in P. polyphylla, could differentiate the macrophage phenotypes by STING to attenuate the tumor-induced immunosuppression in lung cancer.…”

“…20−22 Yu et al 23 al. 21 showed that PPI could inhibit cell proliferation and induce apoptosis by generating reactive oxygen species (ROS), indicating that PPI may activate innate immune signaling through DNA damage due to exposure to ROS. 24,25 Despite these discoveries, it remains unclear whether PPI could serve as a promising chemotherapeutic agent for tumor immunotherapy via innate immune signaling (cGAS/STING pathway).…”

Disruption of Colorectal Cancer Network by Polyphyllins Reveals Pivotal Entities with Implications for Chemoimmunotherapy

“…We envision that an increase in this entity leading to a chromatin level change affecting gene expression in colorectal cancer cells could lead to loss of viability, which we observed at the cellular level in the present study. Additionally, polyphyllins have been reported to inhibit cancer cells by varied mechanisms including reactive oxygen species (ROS) production and DNA damage [45].…”

Effect of Neurorepair for Motor Functional Recovery Enhanced by Total Saponins From Trillium tschonoskii Maxim. Treatment in a Rat Model of Focal Ischemia

“…It's worth noting that TSTT are mainly constituted by two kinds of steroidal saponins, pennogenin, and diosgenin saponins, which possess different biological and pharmacological properties (Hernandez-Vazquez et al, 2020;Ahmad et al, 2021). Specifically, pennogenin saponins have antiinflammatory, anti-tumor and anti-hemorrhagic activity (Wang et al, 2013).…”