Ott_a_287354 1821..1841

1Department of Biology, University of Haripur, KPK, I. R. Pakistan; 2College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, People’s Republic of China; 3Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of China; 4Zoology Department, Hazara University, Mansehra, I. R. Pakistan; 5Biochemistry and Molecular Biology, College of Life Science, Hebei Normal University, Hebei, People’s Republic of China; 6Department of Chemistry, Malakand University, Chakdara, KPK, I. R. Pakistan; 7Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, People’s Republic of China; 8Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical, Dalian City, Liaoning Province, 116011, People’s Republic of China 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.