Pharmacological potentials and Nutritional values of Tropical and Sub-tropical Fruits of India: Emphasis on their anticancer bioactive components

Background: Fruits are an important dietary component, which supply vitamins, minerals, as well as dietary fiber. In addition, they are rich sources of various biological and pharmacologically active compounds. Among these, temperate fruits are well studied for their pharmacological potentials, whereas tropical/subtropical fruits are less explored for their health impacts. In India, most of the consumed fruits are either tropical or subtropical. Objectives: The present review aims to provide a health impact of major tropical and sub-tropical fruits of India, emphasizing their anticancer efficacy. In addition, the identified bioactive components from these fruits exhibiting anticancer efficacy are also discussed along with the patent literature published. Methods: The literature was collected from various repositories, including NCBI, ScienceDirect, Eurekaselect, and Web of Science; literature from predatory journals was omitted during the process. Patent literature was collected from google patents and similar patent databases. Results: Tropical fruits are rich sources of various nutrients and bioactive components including polyphenols, flavonoids, anthocyanin, etc. By virtue of these biomolecules, tropical fruits have been shown to interfere with various steps in carcinogenesis, metastasis, and drug resistance. Their mode of action is either by activation of apoptosis, regulation of cell cycle, inhibition of cell survival and proliferation pathways, increased lipid trafficking or inhibiting inflammatory pathways. Several molecules and combinations have been patented for their anticancer and chemoprotective properties. Conclusion: Overall, the present concludes that Indian tropical/ subtropical fruits are nutritionally and pharmacologically active and may serve as a source of novel anticancer agents in the future.

Crosstalk between adipose and lymphatics in health and disease

Adipose tissue, once thought to be an inert receptacle for energy storage, is now recognized as a complex tissue with multiple resident cell populations which actively collaborate in response to diverse local and systemic metabolic, thermal, and inflammatory signals. A key participant in adipose tissue homeostasis that has only recently captured broad scientific attention is the lymphatic vasculature. The lymphatic system’s role in lipid trafficking and mediating inflammation makes it a natural partner in the regulation of adipose tissue, and evidence supporting a bidirectional relationship between lymphatics and adipose tissue has accumulated in recent years. Obesity is now understood to impair lymphatic function, while altered lymphatic function results in aberrant adipose tissue deposition, though the molecular mechanisms governing these phenomena have yet to be fully elucidated. We will review our current understanding of the relationship between adipose tissue and the lymphatic system here, focusing on known mechanisms of lymphatic-adipose cross-talk.

Interorganelle lipid flux revealed by enzymatic mass tagging in vivo

The distinct activities of cellular organelles are dependent on the proper function of their membranes. Coordinated membrane biogenesis of the different organelles necessitates interorganelle transport of lipids from their site of synthesis to their destination membranes. Several proteins and trafficking pathways have been proposed to participate in lipid distribution, but despite the basic importance of this process, in vivo evidence linking the absence of putative transport pathways to specific transport defects remains scarce. An obvious reason for this scarcity is the near absence of in vivo lipid trafficking assays. Here we introduce a versatile method named METALIC (Mass tagging-Enabled TrAcking of Lipids In Cells) to track interorganelle lipid flux inside living cells. In this strategy, two enzymes, one directed to a "donor" and the other to an "acceptor" organelle, add two distinct mass tags to lipids. Mass spectrometry-based detection of lipids bearing the two mass tags is then used as a proxy for lipid exchange between the two organelles. By applying this approach to ER and mitochondria, we show that the ERMES and Vps13-Mcp1 complexes have lipid transport activity in vivo, and unravel their relative contributions to ER-mitochondria lipid exchange.

Shotgun Proteomic Analysis of Thermally Challenged Reef Corals

Although coral reef ecosystems across the globe are in decline due to climate change and other anthropogenic stressors, certain inshore reefs of the Upper Florida Keys reef tract have persisted, with some even thriving, under marginalized conditions. To better understand the molecular basis of the thermotolerance displayed by these corals, a laboratory-based temperature challenge experiment that also featured conspecifics from a more stress-susceptible offshore reef was conducted with the common Caribbean reef-builder Orbicella faveolata, and the proteomes of both the coral hosts and their endosymbiotic dinoflagellate communities were profiled in (1) controls, (2) corals that succumbed to high-temperature stress and bleached, and (3) those that instead acclimated to high temperatures ex situ. Proteomic signatures varied most significantly across temperatures, host genotypes, and Symbiodiniaceae assemblages, and the two eukaryotic compartments of this mutualism exhibited distinct proteomic responses to high temperatures. Both partners maintained high levels of molecular chaperones and other canonical (eukaryotic) stress response (CSR) proteins in all treatments (including controls). Instead, proteins involved in lipid trafficking, metabolism, and photosynthesis played greater roles in the holobionts’ high-temperature responses, and these energy mobilization processes may have sustained the elevated protein turnover rates associated with the constitutively active CSR.

Investigating the Role of Cholesterol and Lipid Trafficking in Mitotane Resistance in Adrenocortical Carcinoma

Introduction: Adrenocortical Carcinoma (ACC) is a rare aggressive cancer which carries a poor prognosis. Adjuvant mitotane improves survival but is limited by poor response rates and resistance following tumour recurrence. Mitotane’s efficacy has been attributed to intracellular accumulation of toxic free cholesterol (FC) predominantly through inhibition of cholesterol storage through SOAT1. Yet SOAT1 specific inhibitors demonstrate inferior efficacy to mitotane in inducing ACC cell death. We hypothesize that mitotane’s efficacy to induce toxic FC accumulation in ACC cells is also mediated through enhanced breakdown of stored cholesterol within intracellular lipid droplets (LDs). Methodology: ATCC-H295R (mitotane sensitive) and MUC-1 (mitotane resistant) ACC cells were evaluated for neutral lipid content using BODIPY493/503 under baseline and cholesterol loaded conditions using Amnis ImageStream, additionally cells were treated with mitotane (H295R - 20, 40, 50µM; MUC1 - 50, 100, 200µM) for 6hr. Analysis of LDs using CE-BODIPY and FA-BODIPY identified cholesterol ester (CE) and triacylglycerol (TAG)-containing LDs, respectively. Lipid droplet-associated proteins (LDAPs) Perilipin (PLIN) 1–4 and hormone sensitive lipase (HSL) were evaluated using western blotting and PCR. Lipid uptake receptors; SRB1, LDLR, LRP1 and CD36 were measured by flow cytometry. Results: Mitotane treatment, within therapeutic range, decreased staining for LDs significantly in H295R. This was also reflected by decreased expression of LDAPs, PLIN1 and PLIN3. The decrease in H295R LDs was associated with increased activation of HSL (pHSL and LIPE). However, this effect was only evident in MUC-1 at supratherapeutic mitotane (200µM). H295R and MUC-1 demonstrated similar overall LD numbers at baseline and under cholesterol supplementation. Expression of PLIN3 was high in both cell lines, while PLIN1, PLIN2 and PLIN4 demonstrated distinct LD profiles in each. Investigation of LD content showed that H295R preferentially store CEs while MUC-1 store only TAG, irrespective of cholesterol-loading. Mitotane treatment significantly reduces both CE and TAG LDs in H295R and MUC-1. Expression of lipid uptake receptors also demonstrated significant variability between cell lines including SRB1 and LRP1. Conclusion: We highlight that lipolysis through LD breakdown and activation of HSL represents a putative additional mechanism for mitotane induced FC cytotoxicity in ACC. We also demonstrate significant differences in cholesterol handling and LDAPs between mitotane sensitive and mitotane resistant models, in particular, the absence of CE LDs in MUC-1. We therefore propose a mechanism of resistance to mitotane through absent CE storage. Further understanding of cholesterol and lipid handling in ACC offers novel therapeutic exploitation, especially in the setting of mitotane resistant disease.

Brain-specific lipoprotein receptors interact with astrocyte derived apolipoprotein and mediate neuron-glia lipid shuttling

Lipid shuttling between neurons and glia contributes to the development, function, and stress responses of the nervous system. To understand how a neuron acquires its lipid supply from specific lipoproteins and their receptors, we perform combined genetic, transcriptome, and biochemical analyses in the developing Drosophila larval brain. Here we report, the astrocyte-derived secreted lipocalin Glial Lazarillo (GLaz), a homolog of human Apolipoprotein D (APOD), and its neuronal receptor, the brain-specific short isoforms of Drosophila lipophorin receptor 1 (LpR1-short), cooperatively mediate neuron-glia lipid shuttling and support dendrite morphogenesis. The isoform specificity of LpR1 defines its distribution, binding partners, and ability to support proper dendrite growth and synaptic connectivity. By demonstrating physical and functional interactions between GLaz/APOD and LpR1, we elucidate molecular pathways mediating lipid trafficking in the fly brain, and provide in vivo evidence indicating isoform-specific expression of lipoprotein receptors as a key mechanism for regulating cell-type specific lipid recruitment.

Hongyuan Yang: Tracking lipids, one droplet at a time

Hongyuan Yang investigates lipid trafficking and lipid droplet biogenesis.