Lung cancer has been threatening human health worldwide for a long time. However, the clinic therapies remain unsatisfactory. In this study, the anti-adenocarcinoma lung cancer A549 cell line abilities of Tetrastigma hemsleyanum tuber flavonoids (THTF) were evaluated in vivo, and isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis was conducted to detect the protein alterations in THTF-treated solid tumors. The differentially expressed proteins were related to the cytoskeleton and mostly accumulated in the calcium signaling pathway. The in vitro study illustrated that 80 μg mL⁻¹ THTF significantly suppressed cellular viability to approximately 75% of the control. Further results suggested that kaempferol-3-O-rutinoside (K3R), the major component of THTF, effectively triggered cytoskeleton collapse, mitochondrial dysfunction and consequent calcium overload to achieve apoptosis, which remained consistent with proteomic results. This study uncovers a new mechanism for THTF anti-tumor ability, and suggests THTF and K3R as promising anti-cancer agents, providing new ideas and possible strategies for future anti-lung cancer prevention and therapy.

Yellow tea (YT), a slightly-fermented tea originated from Ming Dynasty with distinctive “Three yellows,” mild-sweet smell, and mellow taste attributed to the unique yellowing process. Based on current literature and our previous work, we aim to comprehensively illustrate the key processing procedures, characteristic chemical compounds, health benefits and applications, as well as the interlocking relationships among them. Yellowing is the most vital procedure anchored on the organoleptic quality, characteristic chemical components, and bioactivities of YT, which is influenced by temperature, moisture content, duration, and ventilation conditions. Pheophorbides, carotenoids, thearubigins and theabrownins are the major pigments contributing to the “three yellows” appearance. Alcohols, such as terpinol and nerol, are attributed to the refreshing and sweet aroma of bud and small-leaf YT, while heterocyclics and aromatics forming during roasting result in the crispy rice-like large-leaf YT. Hygrothermal effects and enzymatic reactions during yellowing result in the decline of astringent substances. Meanwhile, multiple bioactive compounds such as catechins, ellagitannins, and vitexin, endow YT with antioxidant, anti-metabolic syndrome, anti-cancer, gut microbiota regulation, and organ injury protection effects. Future studies focusing on the standard yellowing process technology, quality evaluation system, and functional factors and mechanisms, possible orientations, and perspectives are guaranteed.