Xanthorrhizol (XNT) is a bisabolane-type sesquiterpenoid compound extracted from Curcuma xanthorrhiza Roxb. It has been well established to possess a variety of biological activities such as anticancer, antimicrobial, anti-inflammatory, antioxidant, antihyperglycemic, antihypertensive, antiplatelet, nephroprotective, hepatoprotective, estrogenic and anti-estrogenic effects. Since many synthetic drugs possess toxic side effects and are unable to support the increasing prevalence of disease, there is significant interest in developing natural product as new therapeutics. XNT is a very potent natural bioactive compound that could fulfil the current need for new drug discovery. Despite its importance, a comprehensive review of XNT’s pharmacological activities has not been published in the scientific literature to date. Here, the present review aims to summarize the available information in this area, focus on its anticancer properties and indicate the current status of the research. This helps to facilitate the understanding of XNT’s pharmacological role in drug discovery, thus suggesting areas where further research is required.

The Mre11/Rad50/NBN complex plays a central role in coordinating the cellular response to DNA double-strand breaks. The importance of Rad50 in that response is evident from the recent description of a patient with Rad50 deficiency characterized by chromosomal instability and defective ATM-dependent signaling. We report here that ATM (defective in ataxia-telangiectasia) phosphorylates Rad50 at a single site (Ser-635) that plays an important adaptor role in signaling for cell cycle control and DNA repair. Although a Rad50 phosphosite-specific mutant (S635G) supported normal activation of ATM in Rad50-deficient cells, it was defective in correcting DNA damage-induced signaling through the ATM-dependent substrate SMC1. This mutant also failed to correct radiosensitivity, DNA double-strand break repair, and an S-phase checkpoint defect in Rad50-deficient cells. This was not due to disruption of the Mre11/Rad50/NBN complex revealing for the first time that phosphorylation of Rad50 plays a key regulatory role as an adaptor for specific ATM-dependent downstream signaling through SMC1 for DNA repair and cell cycle checkpoint control in the maintenance of genome integrity.

Glioblastoma is deemed the most malignant form of brain tumour, particularly due to its resistance to conventional treatments. A small surviving group of aberrant stem cells termed glioma initiation cells (GICs) that escape surgical debulking are suggested to be the cause of this resistance. Relatively quiescent in nature, GICs are capable of driving tumour recurrence and undergo lineage differentiation. Most importantly, these GICs are resistant to radiotherapy, suggesting that radioresistance contribute to their survival. In a previous study, we demonstrated that GICs had a restricted double strand break (DSB) repair pathway involving predominantly homologous recombination (HR) associated with a lack of functional G1/S checkpoint arrest. This unusual behaviour led to less efficient non‐homologous end joining (NHEJ) repair and overall slower DNA DSB repair kinetics. To determine whether specific targeting of the HR pathway with small molecule inhibitors could increase GIC radiosensitivity, we used the Ataxia‐telangiectasia mutated inhibitor (ATMi) to ablate HR and the DNA‐dependent protein kinase inhibitor (DNA‐PKi) to inhibit NHEJ. Pre‐treatment with ATMi prior to ionizing radiation (IR) exposure prevented HR‐mediated DNA DSB repair as measured by Rad51 foci accumulation. Increased cell death in vitro and improved in vivo animal survival could be observed with combined ATMi and IR treatment. Conversely, DNA‐PKi treatment had minimal impact on GICs ability to resolve DNA DSB after IR with only partial reduction in cell survival, confirming the major role of HR. These results provide a mechanistic insight into the predominant form of DNA DSB repair in GICs, which when targeted may be a potential translational approach to increase patient survival.

Garcinia atriviridis Griff ex T. Anders (G. atroviridis) is one of the well-known species of the genus Garicinia that is native to Thailand, Myanmar, Peninsular Malaysia, and India. G. atroviridis is a perennial medium-sized tree that has a wide range of values, from food to medicinal use. Different parts of G. atroviridis are a great source of bioactive substances that have a positive impact on health. The extracts or bioactive constituents from G. atroviridis have demonstrated various therapeutic functions, including antioxidant, antimicrobial, anticancer, anti-inflammatory, antihyperlipidemic, and anti-diabetic. In this paper, we provide a critical review of G. atroviridis and its bioactive constituents in the prevention and treatment of different diseases, which will provide new insight to explore its putative domains of research.