Calendula officinalis (Asteraceae) as a radiosensitizer in radiotherapy of tumors

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Abstract

The effect of aqueous-alcoholic tincture of Сalendula officinalis L. (Asteraceae) on tumor cells of different species and tissue origin was studied. Its potential as a radiosensitizer in combination with γ-radiation was determined. It has been established that C. officinalis tincture causes the death of tumor cells regardless of their p53 and p21 status. C. officinalis tincture has antioxidant properties, but for cells with active p21 it exhibits radiosensitizing rather than radioprotective properties. For cells lacking p21, C. officinalis tincture is a radioprotector, so the cell death is p21 mediated. A study of the radiosensitizing properties of C. officinalis was carried out on a mouse melanoma model in vivo. In combination with γ-radiation, it led to a significant inhibition of tumor growth (by 47%), as compared to irradiation only. The significant radiosensitizing effect and capability of overcoming the tumor cells resistance induced by p53 inactivation make C. officinalis tincture promising as an add-on to radiotherapy, allowing to reduce the effective radiation dose 1.7 times.

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About the authors

S. D. Koldman

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical Biological Agency

Author for correspondence.
Email: epistularum@yandex.ru
Russian Federation, Moscow

V. A. Koldman

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical Biological Agency; Burnazyan Federal Medical Biophysical Center of the Federal Medical Biological Agency

Email: epistularum@yandex.ru
Russian Federation, Moscow; Moscow

A. V. Belousov

Burnazyan Federal Medical Biophysical Center of the Federal Medical Biological Agency

Email: epistularum@yandex.ru
Russian Federation, Moscow

L. I. Mazaletskaya

Emanuel Institute of Biochemical Physics of Russian Academy of Sciences

Email: epistularum@yandex.ru
Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Kinetic oxygen absorption curves in absence (1) and in presence of Calendula officinalis alcoholic extract (2). Ethylbenzene, 333 K, Wᵢ = 5 × 10 – 8 mol/l s. X-axis – minutes, y-axis – V, relative units.

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3. Fig. 2. Determination of Calendula officinalis cytotoxicity against four tumor cell lines. X-axis – concentration of Calendula officinalis in the culture medium, calculated with reference to dry substance, mg/ml. Y-axis – cell survival as a percentage of control.

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4. Fig. 3. Clonogenic assay of HCT116 line when exposed to radiation doses of 1, 2 and 4 Gy with pre-treatment for 24 hours with 127 μg/ml Calendula officinalis. The number of colonies in untreated control sample was set as 100%. X-axis – total radiation dose, y-axis – clonogenicity, %. Blue – control; red – with C. officinalis pretreatment.

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5. Fig. 4. Clonogenic assay of HCT116p53KO line exposed to radiation doses of 1, 2 and 4 Gy with pre-treatment for 24 hours with 127 μg/ml Calendula officinalis. The number of colonies in untreated control sample was set as 100%. X-axis – total radiation dose, y-axis – clonogenicity, %. Blue – control; red – with C. officinalis pretreatment.

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6. Fig. 5. Photos of colonies of HCT116p53KO cell line. 1 – a sample without exposure, 2 – irradiation at a dose of 1 Gy, 3 – 2 Gy, 4 – 4 Gy, 5 – with pretreatment for 24 hours 127 μg/ml Calendula officinalis, 6 – 127 μg/ml Calendula officinalis + irradiation at a dose of 1 Gy, 7 – 127 μg/ml Calendula officinalis + irradiation at a dose of 2 Gy, 8 – 127 μg/ml Calendula officinalis + irradiation at a dose of 4 Gy.

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7. Fig. 6. Clonogenic assay of HCT116p21KO line exposed to radiation doses of 1, 2, and 4 Gy with pretreatment for 24 hours with 127 μg/ml Calendula officinalis. The number of colonies in untreated control sample was set as 100%. X-axis – total radiation dose, y-axis – clonogenicity, %. Blue – control; red – with C. officinalis pretreatment.

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8. Fig. 7. Inhibition of the growth of transplantable murine melanoma B16 under different conditions. X-axis – days after grafting, y-axis – tumor volume, cm3. Left to right: first line – control; second – Calendula officinalis; third – C. officinalis + 20 Gy; forth – 20 Gy.

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9. Fig. 8. A – control tumor on day 18 after grafting, Б – 31 days after grafting, 22 days after exposure to 20 Gy of γ-radiation in combination with Calendula officinalis pre-treatment, В – site of tumor inoculation 22 days after irradiation in combination with Calendula officinalis pre-treatment.

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