Enhancing the Anti-Cancer Effects of High-Ozonide Oil

Exploiting Cancer’s Oxidative Achilles’ Heel: A Therapeutic Strategy

Cancer cells exhibit a paradoxical relationship with reactive oxygen species (ROS). On one hand, they typically have higher baseline oxidative stress levels than normal cells due to their rapid proliferation, altered metabolism, and genetic instability. This elevated ROS state contributes to oncogenic signaling, promoting further growth and survival adaptations. However, this also places cancer cells in a precarious position, as they rely heavily on robust antioxidant defense mechanisms to maintain redox balance and avoid cell death. This unique vulnerability creates a therapeutic window that can be exploited in cancer treatment.

By strategically elevating ROS levels beyond the cancer cells’ adaptive capacity while simultaneously compromising their antioxidant defenses, it becomes possible to selectively push malignant cells toward oxidative catastrophe and subsequent death. This approach takes advantage of the cancer cells’ already heightened oxidative state, tipping them over the edge into cell death pathways while leaving normal cells relatively unharmed with their lower baseline ROS and more robust antioxidant systems. Various therapeutic strategies can be employed to achieve this, including the use of ROS-generating compounds, inhibitors of antioxidant pathways, and modulators of redox-sensitive signaling cascades.

Core Treatment

High-ozonide oil (HOO) represents a groundbreaking approach in cancer therapy, harnessing the power of targeted oxidative stress to combat malignant cells. This novel compound delivers a potent payload of ozonides directly to cancer cells and cancer stem cells, triggering a catastrophic elevation of intracellular reactive oxygen species (ROS). The resulting oxidative damage proves insurmountable for these malignant cells, leading to their selective destruction while sparing healthy tissue.

In a landmark clinical trial conducted by Professor Alberto Izzotti, MD. PhD and his team, compelling evidence of HOO’s potential to revolutionize cancer treatment was demonstrated:

• An astounding 80% of patients experienced significant clinical benefits, with 44% achieving full recovery and 36% seeing their cancer downstaged.
• Even in notoriously aggressive and treatment-resistant cancers like glioblastoma and pancreatic adenocarcinoma, HOO demonstrated remarkable efficacy.
• Only 10% of patients had stable disease, while a mere 5% experienced progression or passed away.

These outcomes are far superior to those typically observed with standard treatments alone, and they suggest HOO could be a game-changer in oncology, offering new hope for patients facing limited treatment options. By synergizing with conventional therapies and targeting the fundamental metabolic vulnerabilities of cancer cells, HOO represents a promising new frontier in the fight against this devastating disease.

Reference: Izzotti A, Fracchia E, Rosano C, Comite A, Belgioia L, Sciacca S, Khalid Z, Congiu M, Colarossi C, Blanco G, Santoro A, Chiara M, Pulliero A. Efficacy of High-Ozonide Oil in Prevention of Cancer Relapses Mechanisms and Clinical Evidence. Cancers (Basel). 2022 Feb 24;14(5):1174.

Alkalinization Therapy

To maximize the potency of HOO, the tumor microenvironment is alkalinized using bicarbonate. This raises the extracellular pH from the typically acidic to a more alkaline state, stabilizing the ozonides and prolonging their pro-oxidative activity. The alkaline conditions extend the half-life of ozonides and potentially increase their cellular uptake, ensuring a more sustained and penetrating ROS assault on cancer cells and cancer stem cells.

Reference: Isowa M, Hamaguchi R, Narui R, Morikawa H, Okamoto T, Wada H. Potential of Alkalization Therapy for the Management of Metastatic Pancreatic Cancer: A Retrospective Study. Cancers (Basel). 2024;16(1):61.

Inhibiting Glutathione

Building on this enhanced ozonide delivery, the treatment protocol incorporates sulfasalazine—a medication used to treat rheumatoid arthritis and ulcerative colitis—to target glutathione (GSH), a major cellular antioxidant. By inhibiting cystine uptake, sulfasalazine reduces GSH synthesis, lowering cancer cells’ ability to neutralize the ROS generated by the high-ozonide oil. This depletion of GSH leaves cancer cells more vulnerable to the oxidative stress induced by the ozonides.

Reference: Zheng Z, Luo G, Shi X, Long Y, Shen W, Li Z, Zhang X. The X_c^– inhibitor sulfasalazine improves the anti-cancer effect of pharmacological vitamin C in prostate cancer cells via a glutathione-dependent mechanism. Cell Oncol (Dordr). 2020 Feb;43(1):95-106

Inhibiting Thioredoxin

Further complementing the ozonide therapy, auranofin—another medication used to treat rheumatoid arthritis—inhibits the thioredoxin system. This disrup­tion of another critical antioxidant pathway impairs the ability of cancer cells to main­tain redox balance and reduce oxidized proteins. Moreover, it indirectly compromises glutathione peroxidase function, creating a multi-pronged assault on the cells’ antioxi­dant defenses and amplifying the impact of the ozonide-induced ROS.

Reference: Abdalbari FH, Telleria CM. The gold complex auranofin: new perspectives for cancer therapy. Discov Oncol. 2021 Oct 20;12(1):42

Inhibiting Nrf2 Activation

Chrysin—a natural compound found in passionflower—can enhance the effective­ness of ROS-mediated cancer treatments by suppressing the Nrf2-mediated antioxi­dant response in cancer cells. Nrf2 is a master regulator that protects cells from oxidative damage by activating antioxidant genes. By inhibiting Nrf2 activation, chrysin prevents cancer cells from adaptively upregulating their antioxidant defenses in response to oxidative stress. This increases the vulnerability of cancer cells to ROS-induced damage, leading to improved sensitivity to pro-oxidative treat­ments like high-ozonide oil and potentially increased cell death.

Reference: Talebi M, Talebi M, Farkhondeh T, Simal-Gandara J, Kopustinskiene DM, Bernatoniene J, Samarghandian S. Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin. Cancer Cell Int. 2021 Apr 15;21(1):214.

Harnessing Antiparasitic Compounds for Cancer Cell Destruction

The final element in enhancing the efficacy of the high-ozonide oil is niclosamide—a medication used to treat tapeworm infections. Niclosamide exhibits multifaceted anti-cancer effects in cancer cells, primarily by increasing ROS and inducing mito­chondrial stress, leading to apoptosis. It also stimulates autophagy through mTORC1 inhibition, inactivates GSK3β to suppress hedgehog signaling, disrupts Beclin-1/BCL2 interaction to promote autophagic cell death, and induces cell cycle arrest. These mechanisms collectively inhibit cancer cell proliferation, migration, and colony formation. By elevating oxidative stress and modulating multiple signal­ing pathways, niclosamide may enhance the efficacy of other ROS-inducing anti-cancer therapies like high-ozonide oil.

Regular niclosamide should not be used as it has poor bioavailability, meaning it is not well absorbed from the gut into the body. This is fine when treating intestinal parasites but not when treating cancer. When niclosamide is liposomalized, it improves the drug’s absorption and prolongs its duration of action, thereby offering enhanced thera­peutic activity.

Reference: Wang Z, Ren J, Du J, Wang H, Liu J, Wang G. Niclosamide as a Promising Therapeutic Player in Human Cancer and Other Diseases. Int J Mol Sci. 2022 Dec 17;23(24):16116.

Synergistic Effects

The synergistic effects of these strategies, all centered around potentiating the action of high-ozonide oil, create a formidable assault on both cancer cells and cancer stem cells. The alkalinization therapy optimizes the tumor microenvironment for ozonide activity, while sulfasalazine inhibits glutathione synthesis, and auranofin disrupts the thioredoxin system, severely compromising the cells’ antioxidant defenses. Chrysin suppresses the Nrf2-mediated antioxidant response, impairing adaptive mechanisms. Concurrently, niclosamide induces mitochondrial stress and promotes autophagy. With these defenses and adaptive mechanisms impaired, cancer cells are left in a pre­carious state, facing sustained, high levels of ROS gener­ated by the ozonides, which they cannot effectively neutralize.

This multi-faceted approach leads to overwhelming oxidative stress, triggering mul­tiple pathways to cell death, including mitochondrial damage, DNA damage, lipid peroxida­tion, protein oxidation, and ER stress. The additional stress induced by niclosamide further exacerbates this vulnerability, pushing cancer cells beyond their survival thresh­old. Importantly, this strategy leverages the inherently higher baseline ROS levels and unique dependencies of cancer cells, potentially offering a degree of selective toxicity. By pushing cancer cells beyond their redox-adaptive capabilities while leaving normal cells’ more robust defense mechanisms relatively intact, this high-ozonide oil-centered therapy presents a promising strategy for effective, targeted, and potentially less toxic cancer treatment.

Complimenting Standard Cancer Treatments

The protocol may enhance their efficacy for chemotherapy, radiotherapy, and targeted therapies by compromising cancer cells’ antioxidant defenses. The high-ozonide oil generates reactive oxygen species, while sulfasalazine inhibits glutathione syn­thesis and auranofin disrupts the thioredoxin system. Chrysin suppresses the Nrf2-mediated antioxidant response, further impairing adaptive mechanisms. This multi-pronged assault on antioxidant systems could make cancer cells more vulnerable to the oxidative damage caused by chemotherapy and radiotherapy. The alkalinization therapy using bicarbonate may improve the delivery and efficacy of certain chemo­ther­apy drugs by altering the tumor microenvironment. Niclosamide, which can induce mitochondrial stress and promote autophagy, could synergize with targeted therapies that disrupt specific cellular pathways.

The protocol’s effects on the tumor micro­environment could be particularly relevant for hormone blockade and immunotherapy. The alkalinization therapy may create con­ditions that are less favorable for tumor growth and potentially enhance immune cell function. Niclosamide has been shown to improve the efficacy of PD-1/PD-L1 immune check­point blockade in non-small cell lung cancer, suggesting it could potentiate immuno­therapies. By increasing oxidative stress and altering cellular metabolism, the protocol may also make hormone-dependent cancers more sus­ceptible to hormone blockade therapies. Furthermore, the overall weakening of can­cer cells through multiple mecha­nisms (increased ROS, compromised antioxidant systems, mitochondrial stress) could make them more susceptible to immune-mediated destruction, potentially enhancing the effects of various immunotherapies.

Disclaimer

This information is strictly for educational purposes only and should not be construed as personal medical advice. Do not attempt any cancer treatment on your own. Always consult with a qualified healthcare provider.

Additional References

Auranofin:

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6. Li H, Hu J, Wu S, Wang L, Cao X, Zhang X, Dai B, Cao M, Shao R, Zhang R, Majidi M, Ji L, Heymach JV, Wang M, Pan S, Minna J, Mehran RJ, Swisher SG, Roth JA, Fang B. Auranofin-mediated inhibition of PI3K/AKT/mTOR axis and anticancer activity in non-small cell lung cancer cells. Oncotarget. 2016 Jan 19;7(3):3548-58.
7. Liu X, Wang W, Yin Y, Li M, Li H, Xiang H, Xu A, Mei X, Hong B, Lin W. A high-throughput drug screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer. Invest New Drugs. 2019 Dec;37(6):1166-1176.
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9. Nakaya A, Sagawa M, Muto A, Uchida H, Ikeda Y, Kizaki M. The gold com­pound auranofin induces apoptosis of human multiple myeloma cells through both down-regulation of STAT3 and inhibition of NF-κß activity. Leuk Res. 2011 Feb;35(2):243-9.
10. Park SH, Lee JH, Berek JS, Hu MC. Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53. Int J Oncol. 2014 Oct;45(4):1691-8.
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12. Zou P, Chen M, Ji J, Chen W, Chen X, Ying S, Zhang J, Zhang Z, Liu Z, Yang S, Liang G. Auranofin induces apoptosis by ROS-mediated ER stress and mito­chondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer. Oncotarget. 2015 Nov 3;6(34):36505-21.

Bicarbonate:

1. Alfarouk KO, Verduzco D, Rauch C, Muddathir AK, Adil HH, Elhassan GO, Ibrahim ME, David Polo Orozco J, Cardone RA, Reshkin SJ, Harguindey S. Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question. Oncoscience. 2014 Dec 18;1(12):777-802.
2. Boedtkjer E, Pedersen SF. The Acidic Tumor Microenvironment as a Driver of Cancer. Annu Rev Physiol. 2020 Feb 10;82:103-126.
3. Bogdanov A, Verlov N, Bogdanov A, Burdakov V, Semiletov V, Egorenkov V, Volkov N, Moiseyenko V. Tumor alkalization therapy: Misconception or good therapeutics perspective? The case of malignant ascites. Front Oncol. 2024;14:1342802.
4. Hamaguchi R, Isowa M, Narui R, Morikawa H, Okamoto T, Wada H. How Does Cancer Occur? How Should It Be Treated? Treatment from the Perspective of Alkalization Therapy Based on Science-Based Medicine. Biomedicines. 2024 Sep 26;12(10):2197.
5. Hamaguchi R, Isowa M, Narui R, Morikawa H, Wada H. Clinical review of alkalization therapy in cancer treatment. Front Oncol. 2022 Sep 14;12:1003588.
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7. Hamaguchi R, Narui R, Wada H. Effects of Alkalization Therapy on Chemotherapy Outcomes in Metastatic or Recurrent Pancreatic Cancer. Anticancer Res. 2020 Feb;40(2):873-880.
8. Peppicelli S, Andreucci E, Ruzzolini J, Margheri F, Laurenzana A, et al. (2017) Acidity of Microenvironment as a Further Driver of Tumor Metabolic Reprogramming. J Clin Cell Immunol 8: 485.
9. Pilon-Thomas S, Kodumudi KN, El-Kenawi AE, Russell S, Weber AM, Luddy K, Damaghi M, Wojtkowiak JW, Mulé JJ, Ibrahim-Hashim A, Gillies RJ. Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy. Cancer Res. 2016 Mar 15;76(6):1381-90.
10. Wada H, Hamaguchi R, Narui R, Morikawa H. Effects of alkalization therapy on chemotherapy outcomes in advanced pancreatic cancer: A retrospective case-control study. Front Oncol. 2022;12:1003588.
11. Wada H, Hamaguchi R, Narui R, Morikawa H. Meaning and significance of alkalization therapy for cancer. Front Oncol. 2022;12:920843.
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Chrysin:

1. Fu B, Xue J, Li Z, Shi X, Jiang BH, Fang J. Chrysin inhibits expression of hypoxia-inducible factor-1alpha through reducing hypoxia-inducible factor-1alpha stability and inhibiting its protein synthesis. Mol Cancer Ther. 2007 Jan;6(1):220-6.
2. Khoo BY, Chua SL, Balaram P. Apoptotic effects of chrysin in human cancer cell lines. Int J Mol Sci. 2010 May 19;11(5):2188-99.
3. Liu X, Zhang X, Shao Z, Zhong X, Ding X, Wu L, Chen J, He P, Cheng Y, Zhu K, Zheng D, Jing J, Luo T. Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer. Signal Transduct Target Ther. 2023 Dec 18;8(1):463.
4. Moghadam ER, Ang HL, Asnaf SE, Zabolian A, Saleki H, Yavari M, Esmaeili H, Zarrabi A, Ashrafizadeh M, Kumar AP. Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives. Biomolecules. 2020 Sep 27;10(10):1374.
5. Raina R, Bhatt R, Hussain A. Chrysin targets aberrant molecular signatures and pathways in carcinogenesis (Review). World Acad Sci J. 2024 Jun;6:45.
6. Salari N, Faraji F, Jafarpour S, Faraji F, Rasoulpoor S, Dokaneheifard S, Mohammadi M. Anti-cancer Activity of Chrysin in Cancer Therapy: a Systematic Review. Indian J Surg Oncol. 2022 Dec;13(4):681-690.
7. Sood A, Mehrotra A, Sharma U, Aggarwal D, Singh T, Shahwan M, Jairoun AA, Rani I, Ramniwas S, Tuli HS, Yadav V, Kumar M. Advancements and recent explorations of anti-cancer activity of chrysin: from molecular targets to therapeutic perspective. Explor Target Antitumor Ther. 2024;5(3):477-494.
8. Tang X, Luo X, Wang X, Zhang Y, Xie J, Niu X, Lu X, Deng X, Xu Z, Wu F. Chrysin Inhibits TAMs-Mediated Autophagy Activation via CDK1/ULK1 Pathway and Reverses TAMs-Mediated Growth-Promoting Effects in Non-Small Cell Lung Cancer. Pharmaceuticals (Basel). 2024 Apr 17;17(4):515.
9. Talebi M, Talebi M, Farkhondeh T, Simal-Gandara J, Kopustinskiene DM, Bernatoniene J, Samarghandian S. Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin. Cancer Cell Int. 2021 Apr 13;21(1):214.

Niclosamide:

1. Cheng B, Morales LD, Zhang Y, Mito S, Tsin A. Niclosamide induces protein ubiquitination and inhibits multiple pro-survival signaling pathways in the human glioblastoma U-87 MG cell line. PLoS One. 2017 Sep 6;12(9):e0184324.
2. Hamdoun S, Jung P, Efferth T. Drug Repurposing of the Anthelmintic Niclosa­mide to Treat Multidrug-Resistant Leukemia. Front Pharmacol. 2017 Mar 10;8:110.
3. Hsu CW, Huang R, Khuc T, Shou D, Bullock J, Grooby S, Griffin S, Zou C, Little A, Astley H, Xia M. Identification of approved and investigational drugs that inhibit hypoxia-inducible factor-1 signaling. Oncotarget. 2016 Feb 16;7(7):8172-83.
4. Huang M, Qiu Q, Zeng S, Xiao Y, Shi M, Zou Y, Ye Y, Liang L, Yang X, Xu H. Niclosamide inhibits the inflammatory and angiogenic activation of human umbilical vein endothelial cells. Inflamm Res. 2015 Dec;64(12):1023-32.
5. Jeengar MK, Kumar S, Shrivastava S, P SN et al. Niclosamide exerts anti-tumor activity through generation of reactive oxygen species and by sup­pression of Wnt/ β-catenin signaling axis in HGC-27, MKN-74 human gas­tric cancer cells. Asia-Pac J Oncol 2020.
6. Jiang H, Li AM, Ye J. The magic bullet: Niclosamide. Front Oncol. 2022 Nov 21;12:1004978.
7. Jin Y, Lu Z, Ding K, Li J, Du X, Chen C, Sun X, Wu Y, Zhou J, Pan J. Antineoplastic mechanisms of niclosamide in acute myelogenous leukemia stem cells: inactivation of the NF-kappaB pathway and generation of reac­tive oxygen species. Cancer Res. 2010 Mar 15;70(6):2516-27.
8. Kaushal JB, Bhatia R, Kanchan RK, Raut P, Mallapragada S, Ly QP, Batra SK, Rachagani S. Repurposing Niclosamide for Targeting Pancreatic Cancer by Inhibiting Hh/Gli Non-Canonical Axis of Gsk3β. Cancers (Basel). 2021 Jun 22;13(13):3105.
9. Kulthawatsiri T, Kittirat Y, Phetcharaburanin J, Tomacha J, Promraksa B, Wangwiwatsin A, Klanrit P, Titapun A, Loilome W, Namwat N. Metabo­lomic analyses uncover an inhibitory effect of niclosamide on mitochondrial membrane potential in cholangiocarcinoma cells. PeerJ. 2023 Nov 22;11:e16512.
10. Kumar R, Coronel L, Somalanka B, Raju A, Aning OA, An O, Ho YS, Chen S, Mak SY, Hor PY, Yang H, Lakshmanan M, Itoh H, Tan SY, Lim YK, Wong APC, Chew SH, Huynh TH, Goh BC, Lim CY, Tergaonkar V, Cheok CF. Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers. Nat Commun. 2018 Sep 26;9(1):3931.
11. Lee MC, Chen YK, Hsu YJ, Lin BR. Niclosamide inhibits the cell prolifera­tion and enhances the responsiveness of esophageal cancer cells to chemo­therapeutic agents. Oncol Rep. 2020 Feb;43(2):549-561.
12. Li Y, Li PK, Roberts MJ, Arend RC, Samant RS, Buchsbaum DJ. Multi-tar­geted therapy of cancer by niclosamide: A new application for an old drug. Cancer Lett. 2014 Jul 10;349(1):8-14.
13. Lu L, Dong J, Wang L, Xia Q, Zhang D, Kim H, Yin T, Fan S, Shen Q. Acti­vation of STAT3 and Bcl-2 and reduction of reactive oxygen species (ROS) promote radioresistance in breast cancer and overcome of radioresistance with niclosamide. Oncogene. 2018 Sep;37(39):5292-5304.
14. Lu W, Lin C, Roberts MJ, Waud WR, Piazza GA, Li Y. Niclosamide sup­presses cancer cell growth by inducing Wnt co-receptor LRP6 degradation and inhibiting the Wnt/β-catenin pathway. PLoS One. 2011;6(12):e29290.
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17. Pan JX, Ding K, Wang CY. Niclosamide, an old antihelminthic agent, demonstrates antitumor activity by blocking multiple signaling pathways of cancer stem cells. Chinese Journal of Cancer. 2012 Apr;31(4):178-184.
18. Ren J, Wang B, Wu Q, Wang G. Combination of niclosamide and current therapies to overcome resistance for cancer: New frontiers for an old drug. Biomed Pharmacother. 2022 Nov;155:113789.
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23. Wang C, Zhou X, Xu H, Shi X, Zhao J, Yang M, Zhang L, Jin X, Hu Y, Li X, Xiao X, Liao M. Niclosamide Inhibits Cell Growth and Enhances Drug Sensitivity of Hepatocellular Carcinoma Cells via STAT3 Signaling Path­way. J Cancer. 2018 Oct 18;9(22):4150-4155.
24. Wang LH, Xu M, Fu LQ, Chen XY, Yang F. The Antihelminthic Niclosa­mide Inhibits Cancer Stemness, Extracellular Matrix Remodeling, and Metastasis through Dysregulation of the Nuclear β-catenin/c-Myc axis in OSCC. Sci Rep. 2018 Aug 24;8(1):12776.
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26. Xiang M, Chen Z, Yang D, Li H, Zuo Y, Li J, Zhang W, Zhou H, Jiang D, Xu Z, Yu Z. Niclosamide enhances the antitumor effects of radiation by inhibiting the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in human lung cancer cells. Oncol Lett. 2017 Aug;14(2):1933-1938.
27. Yeh LT, Lin CW, Lu KH, Hsieh YH, Yeh CB, Yang SF, Yang JS. Niclosa­mide Suppresses Migration and Invasion of Human Osteosarcoma Cells by Repressing TGFBI Expression via the ERK Signaling Pathway. Int J Mol Sci. 2022 Jan 1;23(1):484.
28. Zhang Q, Yang Z, Hao X, Dandreo LJ, He L, Zhang Y, Wang F, Wu X, Xu L. Niclosamide improves cancer immunotherapy by modulating RNA-binding protein HuR-mediated PD-L1 signaling. Cell Biosci. 2023 Oct 17;13(1):192.

Ozone:

1. Baeza-Noci J, Pinto-Bonilla R. Systemic Review: Ozone: A Potential New Chemotherapy. Int J Mol Sci. 2021 Oct 30;22(21):11796.
2. Li Y, Pu R. Ozone Therapy for Breast Cancer: An Integrative Literature Review. Integr Cancer Ther. 2024 Jan-Dec;23:15347354241226667.

Sulfasalazine:

1. Cramer SL, Saha A, Liu J, Tadi S, Tiziani S, Yan W, Triplett K, Lamb C, Alters SE, Rowlinson S, Zhang YJ, Keating MJ, Huang P, DiGiovanni J, Georgiou G, Stone E. Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth. Nat Med. 2017 Jan;23(1):120-127.
2. Doxsee DW, Gout PW, Kurita T, Lo M, Buckley AR, Wang Y, Xue H, Karp CM, Cutz JC, Cunha GR, Wang YZ. Sulfasalazine-induced cystine starvation: potential use for prostate cancer therapy. Prostate. 2007 Feb 1;67(2):162-71.
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7. Lo M, Ling V, Low C, Wang YZ, Gout PW. Potential use of the anti-inflammatory drug, sulfasalazine, for targeted therapy of pancreatic cancer. Curr Oncol. 2010 Jun;17(3):9-16.
8. Lo M, Wang YZ, Gout PW. The x(c)- cystine/glutamate antiporter: a potential target for therapy of cancer and other diseases. J Cell Physiol. 2008 Jun;215(3):593-602.
9. Shin CS, Mishra P, Watrous JD, Carelli V, D’Aurelio M, Jain M, Chan DC. The glutamate/cystine xCT antiporter antagonizes glutamine metabolism and reduces nutrient flexibility. Nat Commun. 2017 Apr 21;8:15074.
10. Thanee M, Padthaisong S, Suksawat M, Dokduang H, Phetcharaburanin J, Klanrit P, Titapun A, Namwat N, Wangwiwatsin A, Sa-Ngiamwibool P, Khuntikeo N, Saya H, Loilome W. Sulfasalazine modifies metabolic profiles and enhances cisplatin chemosensitivity on cholangiocarcinoma cells in in vitro and in vivo models. Cancer Metab. 2021 Mar 16;9(1):11.