Danshensu, a major water-soluble component of Salvia miltiorrhiza, enhances the radioresponse for Lewis Lung Carcinoma xenografts in mice

Abstract

The molecule 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid (danshensu), a herbal preparation used in traditional Chinese medicine, has been found to possess potential antitumor and anti-angiogenesis effects. The aim of the present study was to investigate the efficacy of the combination of radiation therapy (RT) with danshensu in the treatment of Lewis lung carcinoma (LLC) xenografts, whilst exploring and evaluating the mechanism involved. In total, 8-week old female C57BL/6J mice were randomly assigned into 3 groups to receive: RT, RT + cisplatin and RT + danshensu, respectively, when LLC reached 100–150 mm3. Each group was divided into 7 subgroups according to the different irradiation doses that were administered. Tumor growth curves were created and the sensitization enhancement ratios of the drugs were calculated. The experiment was then repeated, and the 4 groups of tumor-bearing mice were treated with natural saline, danshensu, RT + danshensu and RT, respectively. The mice were sacrificed on day 7, and tumor tissue and blood were collected to determine microvessel density, the expression of proangiogenic factors, and the levels of blood thromboxane B2 and 6-keto-prostaglandin-F1α. Tumor hypoxia was also detected using in vivo fluorescence imaging. With respect to LLC xenografts, treatment with danshensu + RT significantly enhanced the effects of tumor growth inhibition (P<0.05). Furthermore, tumor vasculature was remodeled and microcirculation was improved, which significantly reduced tumor hypoxia (P<0.05). The present study demonstrated that danshensu significantly enhanced the radioresponse of LLC xenografts in mice. The mechanism involved may be associated with the alleviation of tumor cell hypoxia following treatment with danshensu + RT, caused by the improvement of tumor microcirculation and the remodeling of tumor vasculature.

Piperine sensitizes radiation‐resistant cancer cells towards radiation and promotes intrinsic pathway of apoptosis

“…Some natural compounds such as curcumin, quercetin, genistein, (Nicholson et al., 1995) danshsensu, wortmannin, and so on, are reported for inducing radiosensitization in cancer cells (Cao et al., 2017; Javvadi, Segan, Tuttle, & Koumenis, 2008; Lagerweij et al., 2016; Ortiz, Lopez, Burguillos, Edreira, & Pinero, 2004; Tang et al., 2018). Natural products owing to their antioxidant and immune‐enhancing effects may have improved effects as biological and radiation protectors for normal cells.…”

Weipixiao attenuate early angiogenesis in rats with gastric precancerous lesions

“…Essential oil from another member Curcuma zedoaria , a widely used “Hua Yu Tong Luo” herb (function to dissipate blood stasis and free the collateral vessels), presented the anti-angiogenic activity, which therefore contributed to suppressing melanoma growth and lung metastasis [ 26 ]. A recent study suggested that Danshensu, a major water-soluble compound from Salvia miltiorrhiza , could improve microcirculation and remodel tumor vasculature, thereby enhancing the radioresponse for Lewis lung carcinoma xenografts in mice [ 27 ]. The aforementioned researchers revealed the anti-angiogenesis properties of several herbs from WPX.…”

Chalcomoracin inhibits cell proliferation and increases sensitivity to radiotherapy in human non-small cell lung cancer cells via inducing endoplasmic reticulum stress-mediated paraptosis

“…Studies have revealed that natural products can sensitize cancer cells to radiation therapy [ 23 , 24 ]. The mechanisms by which the natural components synergize with IR to facilitate cancer cell killing are usually by enhancing apoptosis, affecting the cell cycle, and/or attenuating angiogenesis [ 25 – 29 ]. In this study, we demonstrated that CMR, a type of Diels–Alder adduct from Mulberry leaves, enhances the radiosensitivity of NSCLC cells by inducing paraptosis.…”