The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

Shiau, Jun‐Ping; Chuang, Ya-Ting; Tang, Jen‐Yang; Yang, Kun-Han; Chang, Fang-Rong; Hou, Ming‐Feng; Yen, Ching‐Yu; Chang, Hsueh-Wei

doi:10.3390/antiox11091845

Cited by 26 publications

(25 citation statements)

References 491 publications

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“…Oxidative stress plays a crucial role in ESC development, making targeted therapy against oxidative stress of significant importance. Currently, NPs have been extensively studied and shown to have the potential in regulating oxidative stress processes[ 82 , 83 ]. These NPs can directly act on tumor cells, exerting anti-ESC effects by modulating multiple oxidative stress pathways.…”

Section: Discussionmentioning

confidence: 99%

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Cao,

Zhang,

Guo

et al. 2024

World J Gastrointest Oncol

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Esophageal cancer (ESC) is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract. Although the exact pathogenesis of ESC has not been fully elucidated, excessive oxidative stress is an important characteristic that leads to the development of many cancers. Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs, which alters the growth and proliferation of ESCs and promotes their metastasis. Natural compounds, including alkaloids, terpenes, polyphenols, and xanthine compounds, can inhibit reactive oxygen species production in ESCs. These compounds reduce oxidative stress levels and subsequently inhibit the occurrence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10, superoxide dismutase, the NF-+ACY-kappa+ADs-B/MAPK pathway, and the mammalian Nrf2/ARE target pathway. Thus, targeting tumor oxidative stress has become a key focus in anti-ESC therapy. This review discusses the potential of Natural products (NPs) for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment. The findings of this review provide a reference for drug development targeting ESCs. Nonetheless, further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

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Section: Discussionmentioning

confidence: 99%

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Cao,

Zhang,

Guo

et al. 2024

World J Gastrointest Oncol

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“…As described, SAMA induces oxidative stress in oral cancer cells, causing apoptosis. Moreover, oxidative stress leads to non-apoptosis types of cancer cell death, such as autophagy and ferroptosis [ 56 , 57 ]. A future thorough examination of non-apoptotic oral cell death in SAMA treatment is necessary.…”

Section: Discussionmentioning

confidence: 99%

Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage

Lu,

Chen,

Yen

et al. 2024

Pharmaceuticals

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The anti-oral cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the anticancer effects and acting mechanism of SAMA against oral cancer (OC-2 and HSC-3) in parallel with normal (Smulow–Glickman; S-G) cells. SAMA selectively inhibits oral cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of reactive oxygen species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral cancer cells at the G2/M phase. SAMA triggers apoptosis (annexin V) in oral cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these anticancer mechanisms of SAMA are more highly expressed in oral cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells.

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“…GSH depletion only partly explained the induction of oxidative stress by DEMU; however, the antioxidant signaling, such as catalase, nuclear factor erythroid 2‐like 2, and superoxide dismutase 57 for regulating oxidative stress, was not examined in this study. Moreover, oxidative stress may trigger several nonapoptotic responses, 58 such as autophagy, ferroptosis, and endoplasmic reticulum stress, which still warrants a detailed investigation of antioral cancer effects of DEMU.…”

Section: Discussionmentioning

confidence: 99%

Demethoxymurrapanine, an indole‐naphthoquinone alkaloid, inhibits the proliferation of oral cancer cells without major side effects on normal cells

Chuang,

Yen,

Shiau

et al. 2023

Environmental Toxicology

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Antioral cancer drugs need a greater antiproliferative impact on cancer than on normal cells. Demethoxymurrapanine (DEMU) inhibits proliferation in several cancer cells, but an in‐depth investigation was necessary. This study evaluated the proliferation‐modulating effects of DEMU, focusing on oral cancer and normal cells. DEMU (0, 2, 3, and 4 μg/mL) at 48 h treatments inhibited the proliferation of oral cancer cells (the cell viability (%) for Ca9‐22 cells was 100.0 ± 2.2, 75.4 ± 5.6, 26.0 ± 3.8, and 15.4 ± 1.4, and for CAL 27 cells was 100.0 ± 9.4, 77.2 ± 5.9, 57.4 ± 10.7, and 27.1 ± 1.1) more strongly than that of normal cells (the cell viability (%) for S‐G cells was 100.0 ± 6.6, 91.0 ± 4.6, 95.0 ± 2.6, and 95.8 ± 5.5), although this was blocked by the antioxidant N‐acetylcysteine. The presence of oxidative stress was evidenced by the increase of reactive oxygen species and mitochondrial superoxide and the downregulation of the cellular antioxidant glutathione in oral cancer cells, but these changes were minor in normal cells. DEMU also caused greater induction of the subG1 phase, extrinsic and intrinsic apoptosis (annexin V and caspases 3, 8, and 9), and DNA damage (γH2AX and 8‐hydroxy‐2‐deoxyguanosine) in oral cancer than in normal cells. N‐acetylcysteine attenuated all these DEMU‐induced changes. Together, these data demonstrate the preferential antiproliferative function of DEMU in oral cancer cells, with the preferential induction of oxidative stress, apoptosis, and DNA damage in these cancer cells, and low cytotoxicity toward normal cells.

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The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

Cited by 26 publications

References 491 publications

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage

Demethoxymurrapanine, an indole‐naphthoquinone alkaloid, inhibits the proliferation of oral cancer cells without major side effects on normal cells

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