Present Status, Challenges, and Prospects of Dihydromyricetin in the Battle against Cancer

Simple Summary With the advancements in diagnosis and treatment technology, the mortality of patients with cancer is gradually decreasing. However, further curbing cancer development requires searching for innovative and more effective drugs. Natural herbal medicine has apparent advantages in R&D and healthcare costs and is attracting increasing attention. Dihydromyricetin is a flavonoid compound with a promising anticancer effect extracted from the stems and leaves of Ampelopsis grossedentata. This paper reviews the different mechanisms of dihydromyricetin alone or in combination with other drugs against a variety of cancers to provide a comprehensive reference for the development of dihydromyricetin as an anticancer therapeutic agent. Dihydromyricetin (DHM) is a natural flavonoid compound extracted from Ampelopsis grossedentata that has been used for centuries in traditional Chinese medicine. DHM has attracted intensive attention due to its numerous beneficial activities, such as hepatoprotection, cardioprotection, antioxidant, and anti-inflammation. In addition, DHM inhibits the progression of cancers such as lung cancer, hepatocellular cancer, breast cancer, melanoma, and malignant reproductive systems through multiple mechanisms, including antiangiogenesis, antiproliferation, apoptosis, and inhibition of invasion and migration. Notably, DHM also activates autophagy at different levels, exerting a dual-regulatory effect on cancers. Mechanistically, DHM can effectively regulate mammalian target of rapamycin (mTOR), noncoding RNA-mediated signaling, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, nuclear factor-kappa B (NF-kappa B), p53, and endoplasmic reticulum stress (ER stress)-driven signaling in different types of cancers. DHM has also been shown to have inhibitory effects on various regulators that trigger epithelial-mesenchymal transition (EMT). Furthermore, DHM exhibits a remarkable anticancer reversal ability when used in combination with drugs such as adriamycin, nedaplatin, and other drugs. However, the low bioavailability of DHM limits its potential applications, which are improved through structural modification and the exploration of novel dosage forms. Therefore, DHM may become a promising candidate for treating malignancies alone or combined with conventional anticancer strategies used in clinical practice.