Index for radiation
Radiation Therapy: Supplements and drugs which sensitize cancer while sparing normal tissues. Left image courtesy of wikimedia.
DCA
134) Cao, Wengang, et al. “Dichloroacetate (DCA) sensitizes
both wild‐type and over expressing Bcl‐2 prostate
cancer cells in vitro to radiation.” The Prostate
68.11 (2008): 1223-1231.
135) Allen, Kah Tan, et al. “Dichloroacetate alters
Warburg metabolism, inhibits cell growth, and
increases the X-ray sensitivity of human A549 and
H1299 NSC lung cancer cells.” Free Radical Biology
and Medicine 89 (2015): 263-273.
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Melatonin : sensitizer and protector
p. 95 Melatonin works in synergy with chemotherapy
and radiation therapy while reducing their
toxicity. (68–71)
p. 96 A number of studies reveal protective
effects of melatonin and ALA against toxic
effects of radiation therapy and chemotherapy
(101–105)
68) Favero, Gaia, et al. “Promising antineoplastic
actions of melatonin.” Frontiers in pharmacology 9
(2018): 1086.
69) Najafi, Masoud, et al. “Adjuvant chemotherapy
with melatonin for targeting human cancers: A review.”
Journal of cellular physiology 234.3 (2019): 2356-2372.
70) Li, Ya, et al. “Melatonin for the prevention and
treatment of cancer.” Oncotarget 8.24 (2017): 39896.
71) Cardinali, D., et al. “Melatonin-Induced Oncostasis,
Mechanisms and Clinical Relevance.” J Integr Oncol S
1 (2016): 2.
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Alonso-González, Carolina, et al. “Melatonin as a radio-sensitizer in cancer.” Biomedicines 8.8 (2020): 247. Different studies have showed that melatonin administered with radiotherapy is able to enhance its therapeutic effects and can protect normal cells against side effects of this treatment.
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Griffin, Fiona, and Laure Marignol. “Therapeutic potential of melatonin for breast cancer radiation therapy patients.” International journal of radiation biology 94.5 (2018): 472-477.
Sanchez-Barcelo, Emilio J., et al. “Melatonin uses in oncology: breast cancer prevention and reduction of the side effects of chemotherapy and radiation.” Expert opinion on investigational drugs 21.6 (2012): 819-831.
Alonso‐González, Carolina, et al. “Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double‐strand DNA break repair.” Journal of pineal research 58.2 (2015): 189-197
Alonso-González, Carolina, et al. “Melatonin enhancement of the radiosensitivity of human breast cancer cells is associated with the modulation of proteins involved in estrogen biosynthesis.” Cancer letters 370.1 (2016): 145-152.
Zetner, Dennis, et al. “MELADERM-trial: melatonin cream against acute radiation dermatitis in patients with early breast cancer.” Melatonin Research 2.1 (2019): 32-43.
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Mortezaee, Keywan, et al. “Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review.” Life sciences 228 (2019): 228-241.
Ben-David, Merav A., et al. “Melatonin for Prevention of Breast Radiation Dermatitis: A Phase II, Prospective, Double-Blind Randomized Trial.” The Israel Medical Association journal: IMAJ 18.3-4 (2016): 188-192.
Karbownik, Małgorzata, and Russel J. Reiter. “Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation.” Proceedings of the Society for Experimental Biology and Medicine: Minireviews 225.1 (2000): 9-22.
Mihandoost, Ehsan, et al. “Can melatonin help us in radiation oncology treatments?.” BioMed research international 2014 (2014).
Shirazi, Alireza, Ghazaleh Ghobadi, and Mahmoud Ghazi-Khansari. “A radiobiological review on melatonin: a novel radioprotector.” Journal of radiation research 48.4 (2007): 263-272.
Erol, Fatih S., et al. “Protective effects of melatonin and vitamin E in brain damage due to gamma radiation.” Neurosurgical Review 27.1 (2004): 65-69.
Nuszkiewicz, Jarosław, Alina Woźniak, and Karolina Szewczyk-Golec. “Ionizing radiation as a source of oxidative stress—the protective role of melatonin and vitamin D.” International journal of molecular sciences 21.16 (2020): 5804.
Şener, Göksel, et al. “Melatonin ameliorates ionizing radiation-induced oxidative organ damage in rats.” Life Sciences 74.5 (2003): 563-572.
Zetner, D., L. P. H. Andersen, and J. Rosenberg. “Melatonin as protection against radiation injury: A systematic review.” Drug research 66.06 (2016): 281-296.
Gürses, İclal, et al. “Histopathological evaluation of melatonin as a protective agent in heart injury induced by radiation in a rat model.” Pathology-Research and Practice 210.12 (2014): 863-871.
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DOXYCYCLINE
p 123 Others have written extensively on the use
of doxycycline as a potential anti-CSC agent and
radiation sensitizer. (40–42)
40) Lokeshwar, Bal L. “Chemically modified non-antimicrobial
tetracyclines are multifunctional drugs
against advanced cancers.” Pharmacological research
63.2 (2011): 146-150.
41) Markowska, Anna, et al. “Doxycycline, salinomycin,
monensin, ivermectin repositioned as cancer drugs.”
Bioorganic & medicinal chemistry letters (2019).
42) Wan, Liyuan, et al. “Aspirin, lysine, mifepristone
and doxycycline combined can effectively and safely
prevent and treat cancer metastasis: prevent seeds
from germinating on soil.” Oncotarget 6.34 (2015):
35157.
Lamb, Rebecca, et al. “Doxycycline down-regulates DNA-PK and radiosensitizes tumor initiating cells: Implications for more effective radiation therapy.” Oncotarget 6.16 (2015): 14005.
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Metformin radiation sensitizer
p 196
Tumor resistance to radiation therapy is
thought to be due to tumor hypoxia, or lack
of oxygen, in the center of the tumor mass.
Metformin reduces oxygen consumption in
the tumor mass by inhibition of complex I of
the ETC, thus increasing oxygen in the cancer
cells and reducing tumor hypoxia. This
increased intracellular oxygen (oxidative therapy)
makes the tumor cells more sensitive to
the killing effects of radiation therapy and the
associated increase in reactive oxygen species
(ROS). (64–66)
64) Zannella, Vanessa E., et al. “Reprogramming
metabolism with metformin improves tumor oxygenation
and radiotherapy response.” Clinical cancer
research 19.24 (2013): 6741-6750
65) Song, Chang W., et al. “Metformin kills and radiosensitizes
cancer cells and preferentially kills cancer
stem cells.” Scientific reports 2 (2012): 362.
66) Brown, Stephen L., et al. “A Novel Mechanism
of High Dose Radiation Sensitization by Metformin.”
Frontiers in oncology 9 (2019): 247.
p 200
Metformin can be used in conjunction with
radiation therapy, chemotherapy (and rituximab)
as a sensitizing agent to augment their
effects. Metformin may be considered an adjuvant
drug for breast cancer patients and other
cancers as well.
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Niclosamide
p 248
In 2019, Dr. So-Yeon Park et al. found
niclosamide effective against colorectal cancer
cell lines in vitro and in vivo xenografts, and
sensitized colon cancer to chemotherapy and
radiotherapy, writing:
49) Park, So-Yeon, et al. “Inhibition of LEF1-mediated
DCLK1 by niclosamide attenuates colorectal cancer
stemness.” Clinical Cancer Research 25.4 (2019):
1415-1429.
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Mebendazole
86) Zhang, Le, et al. “Mebendazole Potentiates
Radiation Therapy in Triple-Negative Breast Cancer.”
International Journal of Radiation Oncology, Biology,
Physics. 103.1 (2019): 195-207.
19) Skibinski, Christine G., Tara Williamson, and
Gregory J. Riggins. “Mebendazole and radiation in
combination increase survival through anticancer
mechanisms in an intracranial rodent model of malignant
meningioma.” Journal of neuro-oncology 140.3
(2018): 529-538.
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Beta Glucans
95) Ghoneum, Mamdooh, et al. “Arabinoxylan rice
bran (MGN-3/Biobran) provides protection against
whole-body γ-irradiation in mice via restoration of
hematopoietic tissues.” Journal of radiation Research
54.3 (2013): 419-429.
===========================
Chloroquine May Augment Standard Chemo-radiation
p 268
In 2016, Dr. Steve Pascolo and others suggested
that the addition of chloroquine to
standard chemo-radiation protocols would
potentiate current anti-cancer treatments.
(80–83)
80) Solomon, V. Raja, and Hoyun Lee. “Chloroquine
and its analogs: a new promise of an old drug for effective
and safe cancer therapies.” European journal of
pharmacology 625.1 (2009): 220-233.
81) Kimura, Tomonori, et al. Chloroquine in cancer
therapy: a double-edged sword of autophagy.” Cancer
research 73.1 (2013): 3-7.
82) Pascolo, Steve. “Time to use a dose of chloroquine
as an adjuvant to anti-cancer chemotherapies.”
European journal of pharmacology 771 (2016):
139-144.
83) Geng, Ying, et al. “Chloroquine-induced autophagic
vacuole accumulation and cell death in glioma
cells is p53 independent.” Neuro-oncology 12.5
(2010): 473-481.
===========================
Thymoquinone
67) Kwan, K., et al. “Thymoquinone Preferentially
Targets Squamous Cell Carcinoma and Demonstrates
Radioprotective Effects on Normal Keratinocytes.”
International Journal of Radiation Oncology Biology
Physics 106.5 (2020): 1188.
68) Kotowski, Ulana, et al. “Effect of thymoquinone
on head and neck squamous cell carcinoma cells in
vitro: Synergism with radiation.” Oncology letters 14.1
(2017): 1147-1151.
———————-=====
82) Ramanan, Sriram, et al. “The PPARα agonist fenofibrate
preserves hippocampal neurogenesis and inhibits
microglial activation after whole-brain irradiation.”
International Journal of Radiation Oncology* Biology*
Physics 75.3 (2009): 870-877.
83) Greene-Schloesser, Dana, et al. “The peroxisomal
proliferator-activated receptor (PPAR) α agonist,
fenofibrate, prevents fractionated whole-brain irradiation-
induced cognitive impairment.” Radiation
research 181.1 (2014): 33-44.
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Celecoxib
p. 487
COX-2 Inhibition Improves Chemo/Radiotherapy
With celecoxib CO-2 inhibition, cancer cells
become dramatically more sensitive to chemotherapy
and radiation therapy. Dr. Hashemi
Goradel and colleagues conclude that COX-2
inhibition should be used as adjuvant with chemotherapy
and radiation therapy:
Therefore, it would be advisable to use
COX‐2 inhibitors as an adjuvant with
chemotherapy and/or radiotherapy. Such
combination has been reported to synergistically
increase the antitumoral activity for
chemotherapeutic agents like sorafenib
5‐fluorouracil, bleomycin, irinotecan,
cisplatin, paclitaxel, carboplatin, sunitinib,
and cetuximab [an EGFR blocker] among
others. This combination also improves the
rate of tolerance to chemo-radiation and
overall response rate for advance stages of
cancers, especially when it is administered
before radiotherapy. (16A)
Synergy with Radiation Therapy
p. 494
Cox-2 inhibitors have been shown to improve
efficacy of radiotherapy by protecting normal
cells and sensitizing tumor cells to the effects
of radiation. This may be related to the pro-oxidant
effect of the COX-2 inhibitor celecoxib as
described by Dr. Ralph below. (80–89)
80) Salehifar, Ebrahim, and Seyed Jalal Hosseinimehr.
“The use of cyclooxygenase-2 inhibitors for improvement
of efficacy of radiotherapy in cancers.” Drug discovery
today 21.4 (2016): 654-662. we discuss the rational basis and molecular mechanisms regarding the usefulness of COX-2 inhibitors in cancer therapy, and also their potential role in increasing the therapeutic index of chemoradiation by protecting normal cells and sensitising tumour cells to radiotherapy.
81) Laube, Markus, Torsten Kniess, and Jens Pietzsch.
“Development of Antioxidant COX-2 Inhibitors as
Radioprotective Agents for Radiation Therapy—A
Hypothesis-Driven Review.” Antioxidants 5.2 (2016):
14.
82) Davis, Thomas W., et al. “Synergy between celecoxib
and radiotherapy results from inhibition of
cyclooxygenase-2-derived prostaglandin E2, a survival
factor for tumor and associated vasculature.” Cancer
research 64.1 (2004): 279-285.
83) Davis, Thomas W., et al. “COX-2 inhibitors as radiosensitizing
agents for cancer therapy.” American journal
of clinical oncology 26.4 (2003): S58-S61.
84) Nakata, Eiko, et al. “Potentiation of tumor response
to radiation or chemoradiation by selective cyclooxygenase-
2 enzyme inhibitors.” International Journal
of Radiation Oncology* Biology* Physics 58.2 (2004):
369-375.
85) Shin, You Keun, et al. “Radiosensitivity enhancement
by celecoxib, a cyclooxygenase (COX)-2 selective
inhibitor, via COX-2–dependent cell cycle regulation
on human cancer cells expressing differential COX-2
levels.” Cancer research 65.20 (2005): 9501-9509.
86) Davis, Thomas W., et al. “Synergy between celecoxib
and radiotherapy results from inhibition of
cyclooxygenase-2-derived prostaglandin E2, a survival
factor for tumor and associated vasculature.” Cancer
research 64.1 (2004): 279-285.
87) Kishi, Kazushi, et al. “Preferential enhancement of
tumor radioresponse by a cyclooxygenase-2 inhibitor.”
Cancer research 60.5 (2000): 1326-1331.
88) Petersen, Cordula, et al. “Enhancement of intrinsic
tumor cell radiosensitivity induced by a selective
cyclooxygenase-2 inhibitor.” Clinical Cancer Research
6.6 (2000): 2513-2520.
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