| Features: treatment category |
| Chemotherapy is a treatment approach that uses drugs to target and kill rapidly dividing cells, primarily cancer cells. However, because many normal cells also divide quickly (such as those in the bone marrow, digestive tract, and hair follicles), chemotherapy can also affect these cells, leading to a range of side effects. Main Classes of Chemotherapy Agents and Examples Alkylating Agents: -work by adding alkyl groups to DNA, which interferes with the DNA’s structure and prevents replication. Examples: Cyclophosphamide, Ifosfamide, Melphalan, Chlorambucil, Busulfan. Anti-metabolites: -interfere with DNA and RNA synthesis by substituting for the normal building blocks of nucleic acids. Examples: Methotrexate, 5-Fluorouracil (5-FU), Cytarabine, Gemcitabine, 6-Mercaptopurine. Anti-microtubule Agents: -interfere with the structures that separate chromosomes during cell division (mitosis). Examples: Paclitaxel, Docetaxel, Vincristine, Vinblastine. Topoisomerase Inhibitors: -target the enzymes topoisomerase I and II, which control the changes in DNA structure required for replication. Examples: Etoposide (topoisomerase II inhibitor), Irinotecan (topoisomerase I inhibitor), Topotecan. Cytotoxic Antibiotics: -intercalate into DNA, inhibiting the replication of cancer cells. Examples: Doxorubicin, Daunorubicin, Bleomycin, Mitoxantrone. Platinum-Based Agents: -contain platinum and cause cross-linking of DNA, which interferes with DNA repair and replication. Examples: Cisplatin, Carboplatin, Oxaliplatin. Many chemotherapy agents exert their effects, at least in part, by inducing oxidative stress in cancer cells. They can increase ROS levels through several mechanisms: -Direct generation of free radicals. -Disruption of mitochondrial function, leading to increased production of ROS. -Interference with the cell’s antioxidant systems. -May want to avoid antioxidants 7 days bef ore and 7 days after chemo. Examples: NAC, Glutathione, Alpha Lipoic Acid, Vitamin E -anti-oxidants known to have pro-oxidant effects (like Quercetin, Curcumin, etc.) should not be taken 2-3 days before and after chemo -pro-oxidants known to bring good benefit to chemo can be continued during chemo. Examples are: Omega 3, Aremisia Annua, Silver NanoParticles. |
| Source: TCGA |
| Type: Antiapoptotic |
| Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. Thought of as "Master Regulator" of antioxidant response. -One way to estimate Nrf2 induction is through the expression of NQO1. NQO1, the most potent inducer: SFN 0.2 μM, quercetin (2.5 μM), curcumin (2.7 μM), Silymarin (3.6 μM), tamoxifen (5.9 μM), genistein (6.2 μM ), beta-carotene (7.2μM), lutein (17 μM), resveratrol (21 μM), indol-3-carbinol (50 μM), chlorophyll (250 μM), alpha-cryptoxanthin (1.8 mM), and zeaxanthin (2.2 mM) 1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects. 2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death. 3. However there are some cases where increasing Nrf2 paradoxically causes an increase in ROS (cancer cells). Such as cases of Mitochondial overload, signal crosstalk, reductive stress -In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies. -Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate. Decreased Nrf2 expression: Skine, Liver, Pancreatic. -Nrf2 is a cytoprotective transcription factor which demonstrated both a negative effect as well as a positive effect on cancer - "promotes Nrf2 translocation from the cytoplasm to the nucleus," means facilitates the movement of Nrf2 into the nucleus, thereby enhancing the cell's antioxidant and cytoprotective responses. -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1. Nrf2 Inhibitors and Activators Nrf2 Inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api - potent Nrf2 inducers from plants include sulforaphane, curcumin, EGCG, resveratrol, caffeic acid phenethyl ester, wasabi, cafestol and kahweol (coffee), cinnamon, ginger, garlic, lycopene, rosemany Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue. – In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis. – In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity. – This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming. – Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies. – High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types. – While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression. NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS). -Brusatol: most cited natural inhibitors of Nrf2. -Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent. -Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: Dose and context dependent . -Oridonin: -Wogonin: although its effects might be cell‑ and dose‑specific. - Withaferin A |
| 2588- | LT, | Chemo, | Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway |
| - | in-vitro, | CRC, | HCT116 |
| 2589- | LT, | Chemo, | Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway |
| - | in-vitro, | BC, | MDA-MB-231 |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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