Targeting the mercapturic acid pathway and vicenin-2 for prevention of prostate cancer

Abstract

Prostate cancer (CaP) is often androgen-sensitive malignancy and regresses upon inhibition of androgen signaling. However, CaP, nearly always develops androgen resistance and progresses to aggressive and lethal androgen-independent CaP, which lacks satisfactory therapy. For metastatic CaP, patients are often treated with Taxotere (docetaxel), a cytoskeleton-targeted chemotherapy drug, that provides transient palliative benefit but to which patients rapidly develop drug-resistance. Combination chemotherapy may be used instead, but is more toxic and adds little clinically relevant benefit over docetaxel. Therefore, novel strategies to enhance docetaxel efficacy are needed to effectively treat patients with metastatic CaP. The mercapturic acid pathway, which metabolizes genotoxic and pro-apoptotic toxins, is over-expressed in CaP and plays an important role in carcinogenesis, metastasis and therapy-resistance of CaP. Vicenin-2, a flavonoid derived from Tulsi (holy basil) as an active compound, inhibits the growth of CaP and increases the anti-tumor activity of docetaxel in-vitro and in-vivo. Taken together, the combination of vicenin-2 and docetaxel could be highly effective in the treatment of advanced and metastatic CaP due to their multi-targeting anti-tumor potential.

Structure Identification of ViceninII Extracted from Dendrobium officinale and the Reversal of TGF-β1-Induced Epithelial–Mesenchymal Transition in Lung Adenocarcinoma Cells through TGF-β/Smad and PI3K/Akt/mTOR Signaling Pathways

“…Due to Chinese medicine theory claims that it clears heat and nourishes the lungs, Dendrobium officinale is widely used in China to treat lung cancer as an adjunctive therapy in order to improve the life quality of patients. ViceninII, a C-glycoside flavonoid extracted from Dendrobium officinale, has been identified and isolated from various medicinal herbs and has shown multiple pharmacological activities, particularly anti-cancer activities [51,52,53], but none of the previous research has focused on the anti-metastasis effects. Therefore, we wondered whether ViceninII could inhibit the TGF-β1-mediated EMT metastasis of lung cancer cells.…”

“…ViceninII, or 6,8-di-C-glucoside of apigenin, a nontoxic flavonoid that was originally identified from Vitex lucens wood and that is present in many plant sources in Southern Asia, such as Dendrobium officinale , Urtica circularis , Lychnophora and other species [40,41,42], is an effective anti-inflammatory [43,44,45,46], antiglycation [47], anti-spasmodic [48], antiseptic [49], antithrombotic, and antiplatelet agent [50]. ViceninII exhibits significant anticancer activities that inhibit the growth of prostate cancer (PC-3, DU-145 and LNCaP cells) in-vitro and in-vivo [51,52] and induce apoptosis in hT-29 human colon cancer cells [53]. In addition, many critical literatures has been reported that ViceninII has shown anti-inflammatory effect through the inhibition of TGF-β-induced protein signaling pathway as well as induced apoptosis of lung cancer H23 cell via PI3K/Akt/mTOR signaling [54,55].…”

Vicenin-2 inhibits Wnt/β-catenin signaling and induces apoptosis in HT-29 human colon cancer cell line

“…Vicenin-2 is a nontoxic flavonoid from the herb Ocimum sanctum Linn and Moringa oleifera , which are widely available in the region of Southern Asia. 12 Vicenin-2 has been reported to possess many pharmacological properties that include antioxidant, hepatoprotective, antiinflammatory, and anticancer effects. 13 Vicenin-2 inhibits angiogenesis and decreases the expression of vascular endothelial growth factor in prostate cancer, and it was proven to be effectively absorbed after oral administration in preclinical models, which was correlated with tumor regression.…”

“… 13 Vicenin-2 inhibits angiogenesis and decreases the expression of vascular endothelial growth factor in prostate cancer, and it was proven to be effectively absorbed after oral administration in preclinical models, which was correlated with tumor regression. 12 …”

Identification of Major Flavone C-Glycosides and Their Optimized Extraction from Cymbidium kanran Using Deep Eutectic Solvents

“…For example, vicenin-2 is a flavone C -glycoside found in diverse plants including Orchidaceae ( Figure 1 a) [ 7 , 8 , 9 ] and has shown various biological activities, including anticancer [ 10 ], anti-inflammatory [ 11 ], and antioxidant effects [ 12 ]. As a result, recent studies on vicenin-2 have focused on various aspects from the quality control of herbal medicine [ 13 ] to organic synthesis [ 14 , 15 ] to the treatment [ 10 ] or prevention [ 16 ] of prostate cancer.…”