Synthetic antioxidants from a natural source can overtake the oncogenic stress management system and activate the stress‑sensitized death of KSHV‑infected cancer cells

Abstract

Synthetic and modified natural derivatives are reported as potential bioactive compounds and are being used therapeutically against various diseases in a widespread manner nowadays. cancerous cells exhibit high levels of reactive oxygen species (ROS) internally, and thus successfully manage to sustain themselves and proliferate via antioxidative mechanisms that maintain a redox balance. On this note, various antioxidants are applied as anticancer compounds, which strategically affects the ongoing oncogenic stress management system in both a pro-and antioxidative manner, resulting in cancer restriction, as well as sustaining cell proliferation via antioxidative mechanisms that promote cancer progression. Alike non-viral cancers, viral cancers exhibit varying levels of ROS during different stages of cancer progression. Hence, successful stress balance should be addressed, depending on the cancer cell stress response during the therapeutic management. The application of antioxidants is crucial and needs to be carefully designed in such cases; the respective underlying mechanisms are less understood. The role of antioxidants controlling the varied levels of stress response at different stages of Kaposi's sarcoma-associated herpes virus malignancy have not been fully reported. Therefore, the present study aimed to analyze the activity of certain antioxidants in KSHV-infected oncogenic cells. For this purpose, two naturally derived flavonoid-based antioxidants (theaflavin and novel curcumin derivatives) were selected and tested in different KSHV-infected cell lines. The findings presented herein demonstrate that these compounds can successfully induce the death of different KSHV-positive cells and can restrict the growth of KSHV-infected cell lines restricting viral reactivation by counteracting the oncogenic stress management system.

Endogenous PTEN acts as the key determinant for mTOR inhibitor sensitivity by inducing the stress-sensitized PTEN-mediated death axis in KSHV-associated malignant cells

“…Autophagic response decides whether a cancerous cell will undergo cell death by overcoming the oncogenic stress response or continue to proliferate. Autophagy may help the cell to overcome stress induction, thus helping the process of adaptation either by cell death with reactivation or drug-insensitive cellular proliferation, ultimately making the cell resistant to chemotherapy ( Das et al, 2022 ). Autophagy is mTOR regulated and can act as stress-responsive signaling in overcoming any kind of stress exposure.…”

“…These cells were cultured in RPMI 1640 media (61870-036, Gibco, United States) with 10% serum (FBS, H1 Australian origin, 10100147, Gibco, United States) and 1% Pen-Strep supplementation (Pen-Strep, 15140-122 Gibco, United States) ( Liu et al, 2001 ). All the cells were maintained in the required aforementioned complete growth media, with or without serum, for the in vitro stress-induced model, which has been utilized in our previous work ( Das et al, 2022 ) at 37°C and 5% CO 2 .…”

“…In relation to this, in our previous work, we have clearly demonstrated such continuous stress balance inside KSHV-associated malignant cells. mTOR has been reported as a major stress-responsive regulatory pathway ( Das et al, 2022 ). Thus, in this study, we intended to critically intersect the role and regulation of PTEN (the principal mTOR regulator) as an oncogenic stress balancer.…”

Curcumin as a Potential Antioxidant in Stress Regulation of Terrestrial, Avian, and Aquatic Animals: A Review

“…Antioxidants 2023, 12, x FOR PEER REVIEW 2 of 33 has been found to prevent organ dysfunction and is recommended as a dietary supplement for obese individuals [8]. Related to counteracting the oncogenic stress management system, curcumin not only causes the death of different Kaposi's sarcoma-associated herpes virus KSHV-positive cells but also obstructs the development of KSHV-infected cells [9]. On the other hand, several studies have been conducted on the role of curcumin in stress management in animal husbandry and aquaculture.…”

Antioxidant and Antibacterial Activity of Endophytic Fungi Isolated from The Leaves of Sungkai (Peronema canescens)

“…[23][24][25] The use of synthetic antioxidants has been reported to trigger mutagenic effects, so natural ingredients are necessary to avoid various kinds of disturbances in the body. [26][27][28][29] Apart from synthetic antioxidants, bacterial resistance has also become the focus of current research. Existing antibiotics possess various disadvantages, including reactions that cause hypersensitivity.…”