Therapeutic Implications of a Polymethoxylated Flavone, Tangeretin, in the Management of Cancer via Modulation of Different Molecular Pathways

Abstract

Chemotherapeutics can induce oxidative stress, inflammation, apoptosis, mitochondrial dysfunction, and abnormalities in neurotransmitter metabolism leading to toxicity. Because there have been no therapeutic strategies developed to target inflammation and oxidative stress, there is a continuing need for new and improved therapy. As a result, there has been increasing interest in complementary and alternative medicine with anticancer potential. Studies have shown that the antioxidant activities and anti-inflammatory effects of citrus fruits are promising natural phytochemicals in the development of new anticancer agents. Tangeretin is a naturally polymethoxylated flavone compound extracted from the citrus peel that has shown significant intestinal absorption and adequate bioavailability, with the added benefit of promoting longevity. In addition, tangeretin is known to exhibit considerable selective toxicity to many types of cancer cell proliferation such as ovarian, brain, blood, and skin cancer. Evidence indicates that tangeretin acts through several mechanisms including growth inhibition, induction of apoptosis, autophagy, antiangiogenesis, and estrogenic-like effects. Furthermore, tangeretin works through mitigating levels of inflammatory mediators in the immune system. Using tangeretin in combination with clinically applied anticancer drugs could be a good strategy for increasing the efficiency of these agents and protecting noncancerous cells from damage caused by chemotherapy. The purpose of this review is to highlight the protective effects of a novel natural product, tangeretin against chemotherapeutic-induced toxicity. The development of chemoprevention strategies can lead to significant health care improvement in cancer survivors. Thus, study outcomes may attract more investigators to conduct tangeretin-related research and find out potentially significant impacts on health care of cancer patients and decreased health problems associated with chemotherapeutics-induced toxicity.

Tangeretin inhibits fungal ferroptosis to suppress rice blast

“…The flavonoid 4,4ʹ‐dimethoxychalcone promotes autophagy‐dependent longevity in yeast (Carmona‐Gutierrez et al, 2019). Tangeretin has also been reported to suppress cancer in mammalian cells by enhancing autophagy (Zheng et al, 2019; Arafa et al, 2021). To explore the possible relationship between tangeretin treatment and autophagy activity in M. oryzae , we tested how tangeretin‐mediated pathogen tolerance responded to treatment with autophagy inducers or inhibitors.…”

Natural flavones from edible and medicinal plants exhibit enormous potential to treat ulcerative colitis

“…Tangeretin is a polymethoxylated dietary flavone existed broadly in citrus plants, involving Citrus unshiu , Citrus reticulata , and Citrus depressa . Studies have proved that tangeretin possesses diversified biological activities, such as anti-inflammation, anti-cancer, and neuroprotection ( Alhamad et al, 2021 ; Arafa et al, 2021 ). Eun et al (2017) studied the therapeutic potential and underlying mechanism of tangeretin in treating UC.…”

An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders

“…A prominent component, in addition to terpenoids and other volatile oils, is PMFs, which are abundant in Citrus peels [14]. Citrus flavonoids, especially methoxylated flavones [15,16], have shown immense therapeutic potential [17]. The most popular Citrus-plant-derived flavonoids include tangeretin (TAN), naringin, hesperidin, nobiletin, naringenin, and hesperetin.…”