2α, 3α, 24-Thrihydroxyurs-12-en-24-ursolic acid enhances the cytotoxic effect of cisplatin on oral cancer cells by down-regulating autophagy.

This study aimed to investigate the effect and mechanism of 2α, 3α, 24-thrihydroxyurs-12-en-24-ursolic acid (TEOA) alone or in combination with cisplatin on oral cancer. TEOA, a pentacyclic triterpenoid compound isolated from the roots of Actinidia eriantha, has demonstrated antitumor activity in preclinical experiments. However, its role in oral cancer remains poorly understood. Our findings revealed that a low concentration of TEOA did not exhibit significant cytotoxicity against oral squamous cell carcinoma cells. However, when combined with cisplatin, TEOA showed a significant therapeutic effect. The combined treatments resulted in a significant inhibition of proliferation and migration and a significant increase in apoptosis of squamous cell carcinoma cells. Cisplatin exposure increased autophagy levels, which may contribute to chemoresistance. Of note, the presence of TEOA significantly inhibited cisplatin-induced autophagy, leading to improved chemotherapy efficacy. Our findings indicate that a mild low dosage of TEOA may enhance the cytotoxic effect of cisplatin by downregulating autophagy in oral cancer cells.

Effects of Temperature, Axial Ligand, and Photoexcitation on the Structure and Spin-State of Nickel(II) Complexes with Water-Soluble 5,10,15,20-Tetrakis(1-methylpyridinium-4-yl)porphyrin.

Water-soluble metalloporphyrins, depending on the metal center, possess special spectral, coordination, and photochemical features. In nickel(II) porphyrins, the Ni(II) center can occur with low-spin or high-spin electronic configuration. In aqueous solution, the cationic nickel(II) complex (Ni(II)TMPyP4+, where H2TMPyP4+ = 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin), exists in both forms in equilibrium. In this study, an equilibrium system involving the low-spin and high-spin forms of Ni(II)TMPyP4+ was investigated via application of irradiation, temperature change, and various potential axial ligands. Soret band excitation of this aqueous system, in the absence of additional axial ligands, resulted in a shift in the equilibrium toward the low-spin species due to the removal of axial solvent ligands. The kinetics and the thermodynamics of the processes were also studied via determination of the rate and equilibrium constants, as well as the ΔS, ΔH, and ΔG values. Temperature increase had a similar effect. The equilibrium of the spin isomers was also shifted by decreasing the solvent polarity (using n-propanol) as well as by the addition of a stronger coordinating axial ligand (such as ammonia). Since triethanolamine is an efficient electron donor in Ni(II)TMPyP4+-based photocatalytic systems, its interaction with this metalloporphyin was also studied. The results promote the development of efficient photocatalytic systems based on this complex.

Designing interfaces of hydrogenase-nanomaterial hybrids for efficient solar conversion.

The direct conversion of sunlight into biofuels is an intriguing alternative to a continued reliance on fossil fuels. Natural photosynthesis has long been investigated both as a potential solution, and as a model for utilizing solar energy to drive a water-to-fuel cycle. The molecules and organizational structure provide a template to inspire the design of efficient molecular systems for photocatalysis. A clear design strategy is the coordination of molecular interactions that match kinetic rates and energetic levels to control the direction and flow of energy from light harvesting to catalysis. Energy transduction and electron-transfer reactions occur through interfaces formed between complexes of donor-acceptor molecules. Although the structures of several of the key biological complexes have been solved, detailed descriptions of many electron-transfer complexes are lacking, which presents a challenge to designing and engineering biomolecular systems for solar conversion. Alternatively, it is possible to couple the catalytic power of biological enzymes to light harvesting by semiconductor nanomaterials. In these molecules, surface chemistry and structure can be designed using ligands. The passivation effect of the ligand can also dramatically affect the photophysical properties of the semiconductor, and energetics of external charge-transfer. The length, degree of bond saturation (aromaticity), and solvent exposed functional groups of ligands can be manipulated to further tune the interface to control molecular assembly, and complex stability in photocatalytic hybrids. The results of this research show how ligand selection is critical to designing molecular interfaces that promote efficient self-assembly, charge-transfer and photocatalysis. This article is part of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems.

Corrigendum: TEOA inhibits proliferation and induces DNA damage of diffuse large B-cell lymphoma cells through activation of the ROS-dependent p38 MAPK signaling pathway.

[This corrects the article DOI: 10.3389/fphar.2020.554736.].

TEOA Promotes Autophagic Cell Death via ROS-Mediated Inhibition of mTOR/p70S6k Signaling Pathway in Pancreatic Cancer Cells.

Pancreatic cancer is a common malignant tumor with high mortality, and novel therapeutic options have focused on ameliorating its poor prognosis. TEOA, a traditional Chinese herbal medicine, exhibits anti-inflammatory and anti-cancer activities. Our recent study has shown that TEOA inhibits proliferation and induces DNA damage in diffuse large B-cell lymphoma cells by activating the ROS-mediated p38 MAPK pathway. However, its effects on pancreatic cancer cells remain unknown. In the present study, we evaluated the effects of TEOA on the proliferation, migration of pancreatic cancer cells and explored the possible underlying mechanism of action. We found that TEOA significantly inhibited the proliferation and migration of pancreatic cancer cells in a time- and dose-dependent manner. Mechanistically, TEOA significantly induced mitochondrial dysfunction in PANC1 and SW1990 cells, as evidenced by the collapse of the mitochondrial membrane potential, exhausted ATP level, and excessive accumulation of intracellular ROS. Notably, our further experiments showed that TEOA induced autophagic cell death in pancreatic ductal adenocarcinoma cells by inactivating the ROS-dependent mTOR/p70S6k signaling pathway. More importantly, both pharmacological or genetic blocking of the autophagic flux signal could partly restore the cytotoxicity of TEOA, whereas activation of autophagy by rapamycin or EBSS induced starvation facilitated the cytotoxicity of TEOA. Concomitantly, N-acetylcysteine, a ROS scavenger, abolished the inhibition of the mTOR signaling pathway, thus preventing autophagy and restoring cell viability. Taken together, our results reveal that TEOA can lead to ROS-dependent autophagic cell death of pancreatic cancer cells by inducing mitochondrial dysfunction, which might be a promising therapeutic agent for pancreatic cancer.

TEOA Inhibits Proliferation and Induces DNA Damage of Diffuse Large B-Cell Lymphoma Cells Through Activation of the ROS-Dependent p38 MAPK Signaling Pathway.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for approximately 30% to 40% of non-Hodgkin's lymphomas (NHL). The administration of rituximab significantly improved the outcomes of DLBCL; however, the unavoidable development of resistance limits the long-term efficacy. Therefore, a new generation of less toxic drugs with higher chemotherapy response is required to prevent or reverse chemoresistance. TEOA is a pentacyclic triterpenoid compound isolated from the roots of Actinidia eriantha. Studies have confirmed that TEOA has significant cytotoxicity on gastrointestinal cancer cells. However, there are no relevant reports on DLBCL cells. In this study, we investigated the potential molecular mechanism of the anticancer activity of TEOA in DLBCL cells. The results demonstrated that TEOA inhibited proliferation and induced apoptosis in time-and dose-dependent manners. TEOA induced reactive oxygen species (ROS) generation, which was reversed by N-acetyl cysteine (NAC). TEOA induced DNA damage, increased the level of γ-H2AX, and the phosphorylation of CHK1 and CHK2. In addition, TEOA induced the activation of the p38 MAPK pathway and pretreated with p38 inhibitor SB20358 or ROS scavenger could block TEOA-induced DNA damage. Taken together, these results suggest that ROS mediated activation of the p38 MAPK signal pathway plays an important role in initiating TEOA-induced DNA damage.

TEOA, a triterpenoid from Actinidia eriantha, induces autophagy in SW620 cells via endoplasmic reticulum stress and ROS-dependent mitophagy.

2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62. Further analysis illustrated that TEOA promoted the phosphorylation of PERK and elF2α, followed by up-regulation of the downstream protein CHOP, suggesting the involvement of PERK/eIF2α/CHOP pathway and ER stress in TEOA-induced autophagy in SW620 cells. Meanwhile, TEOA-mediated PINK1, Parkin, ubiquitin and p62 activation revealed that TEOA induced specific autophagy-mitophagy in SW620 cells. Additionally, an antioxidant NAC attenuated the TEOA-induced mitophagy, indicating that TEOA triggers mitophagy via a ROS-dependent pathway. Collectively, our findings revealed a novel cellular mechanism of TEOA in the colon cancer cell line SW620, thus providing a molecular basis for developing TEOA into an anti-tumor candidate.

Interaction between triethanolamine and singlet or triplet excited state of xanthene dyes in aqueous solution.

Triethanolamine (TEOA) has been often used as a hole-scavenger in dye-sensitized semiconductor photocatalytic systems. However, the femtosecond time-resolved kinetics of the interaction between a sensitized dye and TEOA has not been reported in literatures. Herein, we selected four commonly used xanthene dyes, such as fluorescein, dibromofluorescein, eosin Y, and erythrosine B, and studied their ultrafast fluorescence quenching dynamics in the presence of TEOA in aqueous solution, respectively, by using both femtosecond transient absorption and time-resolved fluorescence measurements. We obtained the electron transfer rate from TEOA to each photoexcited xanthene dye in 2.0 M TEOA solution. We also obtained the intersystem crossing rate of each xanthene dye in aqueous solution with fluorescence quantum yield and lifetime measurements. Finally we found that TEOA mainly interacts with the singlet excited-state of fluorescein, dibromofluorescein, and eosin Y, and that TEOA can interact with both the singlet and triplet excited-states of erythrosine B in high concentration of TEOA aqueous solution.