Human pancreatic tumor cells have an intrinsic ability to tolerate nutrition starvation and survive in the hypovascular tumor microenvironment, the phenomenon termed as “austerity”. Searching for an agent that inhibits such tolerance to nutrient starvation and kills the pancreatic cancer cells preferentially in nutrient-starvation is a unique anti-austerity strategy in anti-cancer drug discovery. In this strategy, plant extracts and compounds are tested against PANC-1 human pancreatic cancer cell line under the conditions of nutrient-deprived medium (NDM) and nutrient-rich medium (DMEM), to discover the compounds that show selective cytotoxicity in NDM. Screening of twenty-five Thai indigenous medicinal plant extracts for their anti-austerity activity against the PANC-1 human pancreatic cancer cell line in nutrient deprived medium (NDM) resulted in the identification of four active plants, Derris scandens, Boesenbergia pandurata, Citrus hystrix, and Kaempferia parviflora, with PC₅₀ values 0.5–8.9 µg/mL. K. parviflora extract also inhibited PANC-1 cancer cell colony formation. Phytochemical investigation of K. parviflora extract led to the isolation of fourteen compounds, including two polyoxygenated cyclohexanes (1 and 2), eleven flavonoids (3–13), and β-sitosterol (14). Stereochemical assignment of compound 1 was confirmed through X-ray analysis. All isolated compounds were tested for their preferential cytotoxicity against PANC-1 cells. Among them, 5-hydroxy-7-methoxyflavone (3) displayed the most potent activity with a PC₅₀ value of 0.8 µM. Mechanistically, it was found to induce apoptosis in PANC-1 cell death in NDM as evident by caspase cleavage. It was also found to inhibit PANC-1 cancer cell colony formation in DMEM. Therefore, compound 3 can be considered as a potential lead compound for the anticancer drug development based on the anti-austerity strategy.

Ethanolic extract of Nelumbo nucifera petals showed preferential cytotoxic activity against HeLa human cervical cancer cell line with a PC₅₀ value of 10.4 μg/mL. This active extract was subjected to a phytochemical investigation study which led to the isolation of nine benzylisoquinoline alkaloids (1–9). The isolated compounds exhibited potent antiausterity activities. Moreover, under nutrient-deprived conditions, (−)-lirinidine (8) induced remarkable alterations in HeLa cell morphology including cell shrinkage and plasma blebbing leading to total cell death within 10 h. Mechanistically, 8 was found to inhibit Akt/mTOR signaling pathway. It also induced apoptosis by promoting caspase-3 activation and inhibiting Bcl-2 expression. Therefore, benzylisoquinoline alkaloids skeleton can be considered as a promising scaffold for the anticancer drug development against cervical cancer.

Background Chronic stress exposure has been widely recognized as a significant contributor to numerous central nervous system (CNS) disorders, leading to debilitating behavioral changes such as anxiety, depression, and cognitive impairments. The prolonged activation of the hypothalamic–pituitary–adrenal (HPA) axis during chronic stress disrupts the neuroendocrine balance and has detrimental effects on neuronal function and survival. Nelumbo nucifera (N. nucifera) Gaertn., commonly known as the lotus flower, is a traditional medicinal plant consumed for its purported benefits on mental and physical well-being. Despite its traditional use, limited scientific evidence supports these claims. Methods The present study explores the effects of N. nucifera, commonly known as the lotus flower, on cognitive performance and stress resilience in a mouse model subjected to unpredictable chronic mild stress (UCMS). Results Daily treatment significantly improved cognitive performance, alleviated depressive-like behaviors, and normalized hypothalamic–pituitary–adrenal (HPA) axis activity, as indicated by a 60.97% reduction in serum corticosterone. At the molecular level, N. nucifera petals also downregulated serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression while upregulating brain-derived neurotrophic factor (BDNF) mRNA expression and cyclic-adenosine monophosphate (cAMP) responsive element-binding protein (CREB) mRNA expression in the hippocampus and frontal cortex. These normalizations are critical, as chronic stress dysregulates HPA axis function, exacerbating behavioral changes. Furthermore, a phytochemical analysis resulted in the isolation of five major compounds, kaempferol (1), trifolin (2), kaempferol-3-neohesperidoside (3), icariside D₂ (4), and β-sitosterol (5), each demonstrating significant monoamine oxidase (MAO) inhibitory activity. Conclusions These compelling findings suggest that N. nucifera petals not only alleviate stress-induced mood and cognitive deficits but also offer a promising avenue for modulating the HPA axis and promoting neuroprotection via essential neurotrophic factors and enzymatic pathways. We advocate for its potential as a complementary and alternative medicine for effective stress management. Future investigations should further explore its mechanisms of action and evaluate its clinical applicability in stress-related disorders.

An n-hexane extract of Callistemon subulatus was found to exhibit potent cytotoxicity against PANC-1 human pancreatic cancer cells, preferentially under nutrition starvation conditions, with a PC₅₀ value of 6.2 µg/mL. Phytochemical investigation of this bioactive extract resulted in the isolation of fifteen compounds (1–15), including a new compound, subulatone A (–). The structure of compound 1 was elucidated using HRFABMS and NMR spectroscopic analyses. The isolated compounds were tested for their preferential cytotoxicity against the PANC-1 human pancreatic cancer cell line, using an anti-austerity strategy. Among these, myrtucommulone A (2) showed highly potent preferential cytotoxicity, with a PC₅₀ value of 0.28 µM. Myrtucommulone A (2) was found to alter PANC-1 cell morphology, inhibit cell migration, and downregulate the PI3K/Akt/mTOR and autophagy signaling pathways in nutrient-deprived media, leading to cancer cell death. Therefore, myrtucommulone A (2) is a lead compound for anticancer drug development based on an anti-austerity strategy.

Aim: Simultaneous inhibition of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) may enhance anti-HCV effects and reduce resistance and side effects. Results/methodology: Novel hybrid derivatives were designed and synthesized to exhibit dual activity against HCV and its associated major complication, HCC. The synthesized compounds were screened for their potential activity against HCV and HCC. Compounds 5f, 5j, 5l, 5p, 5q, 5r, 6c and 6d exhibited potential in vitro anticancer activity against HCC cell line HepG2, while compounds 5a, 5l, 5p and 5v showed in vitro anti-HCV activity. Docking studies suggested that the newly synthesized compounds could suppress HCC through VEGFR2 tyrosine kinase inhibition. Conclusion: Compounds 5l and 5p exhibited dual activity against HCV and HCC in vitro. Lay abstract There is a close relation between chronic hepatitis C virus (HCV) infection and development of hepatocellular carcinoma (HCC). Dual inhibition of HCV and HCC could enhance anti-HCV activity and reduce resistance of HCC to treatment. Novel compounds were designed and synthesized to exhibit dual activity against HCV and HCC. The synthesized compounds were screened for their potential in vitro activity against HCV and the HCC HepG2 cell line. Compounds 5l and 5p exhibited dual activity against HCV and HCC in vitro. Further studies predicted that the target compounds could suppress HCC. Graphical abstract

Metastasis is a hallmark of cancer that is responsible for the greatest number of cancer-related deaths (~90%). For the metastasis to take place, the primary tumor mass engineers migratory cells that can invade adjacent tissues and circulate to distant organs where cancer cells have sufficient nutrients to grow and form new colonies. The migrating cell group typically consists of “LEADER” cells at the front, which navigate the path lead collective invasive packs, and “FOLLOWER” cells that trail behind and support the movement. Both leader and follower cells communicate and cooperate to achieve collective cancer migration and invasion. Recent studies showed that the elimination of a leader cell disrupts collective cell migration. However, The mechanisms controlling the synchronized migration of leader and follower cells are still unresolved. Therefore, the genetic and metabolic traits of leader and follower cells, enabling them to navigate their way into secondary nutrient-rich sites and escape the immune system surveillance, need further elucidation. Interestingly, the differential Multi-omic analyses of cancer leader and follower cells are an emerging area of research within the study of tumor heterogeneity and metastasis. This review highlights the recent findings about leader/follower cancer cells focusing on their unique proteomic, metabolic, and transcriptomic signatures rendering them their unique involvement in cancer metastasis and invasion.